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Sample records for inactivated trivalent influenza

  1. Seasonal trivalent inactivated influenza vaccine protects against 1918 Spanish influenza virus in ferrets

    Science.gov (United States)

    The influenza H1N1 pandemic of 1918 was one of the worst medical disasters in human history. Recent studies have demonstrated that the hemagglutinin (HA) protein of the 1918 virus and 2009 H1N1 pandemic virus, the latter now a component of the seasonal trivalent inactivated influenza vaccine (TIV),...

  2. Immunogenicity and safety of a trivalent inactivated influenza vaccine

    Directory of Open Access Journals (Sweden)

    Eddy Fadlyana

    2011-02-01

    Full Text Available Background Trivalent inactivated influenza vaccines (TIV containing antigens of two influenza A strains, A(H1N1 and A(H3N2, and one influenza B strain, are the standard {onnulation for influenza prevention. The vaccines must be updated annually to provide optimal protection against the predicted prevalent strains for the next influenza season. Objective To assess the immunogenidty and safety of the inactivated influenza vaccine (Flubio® in adolescents and adults, 28 days after a single dose. Methods In this experimental, randomized, single-blind, bridging study, we included 60 healthy adolescents and adults. A single, 0.5 mL dose was administered intramuscularly in the deltoid muscle of the left ann. Blood samples were obtained before and 28 days after immunization. Standardized hemagglutination inhibition (HI test was used to assess antibody response to influenza antigens. Results From January to February 2010, a total of 60 adolescents and adults enrolled in the study, but two participants did not provide the required blood samples. One hundred percent of the subjects had an anti-influenza titer ≥ 1:40 HI units to all three strains, A/Brisbane/59/2007 (H1N1, A/Uruguay/716/2007 (H3N2, and B/Brisbane/60/2008 (P=1.000 after immunization. The Geometric Mean Titers (GMT after immunization increased for all strains: A/Brisbane, 76.4 to 992.7, A/Uruguay, 27.6 to 432.1, and B/Brisbane, 19.9 to 312.7. Twenty eight days after immunization, we found a 4 times increase in antibody titers in 75.8% of the subjects for A/Brisbane, 84.5% for A/Uruguay, and 77.6% for B/Brisbane. We also observed that 100% of seronegative subjects converted to seropositive for all 3 strains. All vaccines were well-tolerated. There were no serious adverse events reported during the study. Conclusion In adolescents and adults, the Flubio® vaccine was immunogenic and safe.

  3. Antibody Responses to Trivalent Inactivated Influenza Vaccine in Health Care Personnel Previously Vaccinated and Vaccinated for The First Time

    OpenAIRE

    Kuan-Ying A. Huang; Shih-Cheng Chang; Yhu-Chering Huang; Cheng-Hsun Chiu; Tzou-Yien Lin

    2017-01-01

    Inactivated influenza vaccination induces a hemagglutinin-specific antibody response to the strain used for immunization. Annual vaccination is strongly recommended for health care personnel. However, it is debatable if repeated vaccination would affect the antibody response to inactivated influenza vaccine through the time. We enrolled health care personnel who had repeated and first trivalent inactivated influenza vaccination in 2005?2008. Serological antibody responses were measured by hem...

  4. Safety and immunogenicity of a quadrivalent inactivated influenza vaccine compared to licensed trivalent inactivated influenza vaccines in adults.

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    Greenberg, David P; Robertson, Corwin A; Noss, Michael J; Blatter, Mark M; Biedenbender, Rex; Decker, Michael D

    2013-01-21

    To evaluate the safety and immunogenicity of a prototype quadrivalent inactivated influenza vaccine (QIV) containing two influenza B strains, one of each lineage, compared with licensed trivalent inactivated influenza vaccines (TIVs) containing either a Victoria B-lineage strain (2009-2010 TIV) or a Yamagata B-lineage strain (2008-2009 TIV). Healthy adults ≥18 years of age were eligible to participate in this phase II, open-label, randomized, controlled, multicenter study conducted in the US. Participants received a single dose of 2009-2010 TIV, 2008-2009 TIV, or QIV. Sera were collected before and 21 days after vaccine administration to test for hemagglutination inhibition (HAI) antibodies to each of the four influenza strains. Immunogenicity endpoints included geometric mean HAI antibody titers (GMTs) and rates of seroprotection (titer ≥1:40) and seroconversion (4-fold rise pre- to post-vaccination). Safety endpoints included frequency of solicited injection-site and systemic reactions occurring within 3 days of vaccination, and unsolicited non-serious adverse events (AEs) and serious AEs (SAEs) within 21 days of vaccination. One hundred and ninety participants were enrolled to each vaccine group. QIV induced GMTs to each A and B strain that were noninferior to those induced by the 2009-2010 and 2008-2009 TIVs (i.e., lower limit of the two-sided 95% confidence interval of the ratio of GMT(QIV)/GMT(TIV)>0.66 for each strain). Rates of seroprotection and seroconversion were similar in all groups. Incidence and severity of solicited injection-site and systemic reactions, AEs, and SAEs were similar among groups. QIV, containing two B strains (one from each B lineage), was as safe and immunogenic as licensed TIV. QIV has the potential to be a useful alternative to TIV and offer protection against both B lineages. Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. The effectiveness of seasonal trivalent inactivated influenza vaccine in preventing laboratory confirmed influenza hospitalisations in Auckland, New Zealand in 2012

    Science.gov (United States)

    Turner, Nikki; Pierse, Nevil; Bissielo, Ange; Huang, Q Sue; Baker, Michael; Widdowson, Marc-Alain; Kelly, Heath

    2015-01-01

    Background Few studies report the effectiveness of trivalent inactivated influenza vaccine (TIV) in preventing hospitalisation for influenza-confirmed respiratory infections. Using a prospective surveillance platform, this study reports the first such estimate from a well-defined ethnically diverse population in New Zealand (NZ). Methods A case test-negative study was used to estimate propensity adjusted vaccine effectiveness. Patients with a severe acute respiratory infection (SARI), defined as a patient of any age requiring hospitalization with a history of a fever or a measured temperature ≥38°C and cough and onset within the past 7 days, admitted to public hospitals in Central, South and East Auckland were eligible for inclusion in the study. Cases were SARI patients who tested positive for influenza, while non-cases (controls) were SARI patients who tested negative. Results were adjusted for the propensity to be vaccinated and the timing of the influenza season Results The propensity and season adjusted vaccine effectiveness (VE) was estimated as 37% (95% CI 18;51). The VE point estimate against influenza A (H1N1) was higher than for influenza B or influenza A (H3N2) but confidence intervals were wide and overlapping. Estimated VE was 51% (95% CI 28;67) in patients aged 18-64 years but only 6% (95% CI -51;42) in those aged 65 years and above. Conclusion Prospective surveillance for SARI has been successfully established in NZ . This study for the first year, the 2012 influenza season, has shown low to moderate protection by TIV against hospitalisation for laboratory-confirmed influenza. PMID:24768730

  6. Association of HLA class II genes with clinical hyporesponsiveness to trivalent inactivated influenza vaccine in children.

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    Narwaney, Komal J; Glanz, Jason M; Norris, Jill M; Fingerlin, Tasha E; Hokanson, John E; Rewers, Marian; Hambidge, Simon J

    2013-02-04

    The primary prevention measure for influenza infection has been the use of influenza vaccines. However, even when the vaccine and circulating strains are well-matched, some healthy children do not respond to the vaccine, likely due to a genetic basis for immune hyporesponsiveness. The primary objective of this study was to identify HLA class II genes associated with clinical hyporesponsiveness after trivalent inactivated influenza vaccine (TIV) in children. We conducted a case-control study nested within a retrospective cohort of children that were screened at birth for HLA-DR,DQ genotypes by the Diabetes Autoimmunity Study in the Young (DAISY) and were subsequently followed for up to 8 years by Kaiser Permanente, Colorado (KPCO). Hyporesponsiveness was clinically defined as the occurrence of influenza or influenza-like illness (ILI) in peak influenza weeks in children fully vaccinated with TIV. Each child with clinical hyporesponse (n=252) was matched to 4 randomly selected controls (n=1006) by age and season. Children with clinical hyporesponse to TIV were identified using the Kaiser electronic clinical and immunization databases. Fully vaccinated children within the KPCO-DAISY cohort who did not have a diagnosis of ILI during the entire influenza season were eligible to be controls for that season. Class II HLA-DRB1 and HLA-DQB1 genes were the primary exposure variables. We used conditional logistic regression to calculate the matched odds ratios. In non-Hispanic white children, HLA-DR7/4,DQB1 0302 genotype was significantly associated (OR=5.15; 95% CI=1.94, 13.67; p=0.001), while in Hispanic children, HLA-DRB1 15 or 16 allele (OR=0.31; 95% CI=0.14, 0.69; p=0.004) and HLA-DR7/Y (DRB1 11, DRB1 13 and DRB1 14) genotype (OR=5.84; 95% CI=1.68, 20.28; p=0.006) were significantly associated with clinical hyporesponsiveness after TIV. HLA class II genes are associated with clinical hyporesponsiveness to TIV. This finding is important as it may help identify a group of

  7. Partial protection of seasonal trivalent inactivated vaccine against novel pandemic influenza A/H1N1 2009: case-control study in Mexico City.

    Science.gov (United States)

    Garcia-Garcia, Lourdes; Valdespino-Gómez, Jose Luis; Lazcano-Ponce, Eduardo; Jimenez-Corona, Aida; Higuera-Iglesias, Anjarath; Cruz-Hervert, Pablo; Cano-Arellano, Bulmaro; Garcia-Anaya, Antonio; Ferreira-Guerrero, Elizabeth; Baez-Saldaña, Renata; Ferreyra-Reyes, Leticia; Ponce-de-León-Rosales, Samuel; Alpuche-Aranda, Celia; Rodriguez-López, Mario Henry; Perez-Padilla, Rogelio; Hernandez-Avila, Mauricio

    2009-10-06

    To evaluate the association of 2008-9 seasonal trivalent inactivated vaccine with cases of influenza A/H1N1 during the epidemic in Mexico. Frequency matched case-control study. Specialty hospital in Mexico City, March to May 2009. 60 patients with laboratory confirmed influenza A/H1N1 and 180 controls with other diseases (not influenza-like illness or pneumonia) living in Mexico City or the State of Mexico and matched for age and socioeconomic status. Odds ratio and effectiveness of trivalent inactivated vaccine against influenza A/H1N1. Cases were more likely than controls to be admitted to hospital, undergo invasive mechanical ventilation, and die. Controls were more likely than cases to have chronic conditions that conferred a higher risk of influenza related complications. In the multivariate model, influenza A/H1N1 was independently associated with trivalent inactivated vaccine (odds ratio 0.27, 95% confidence interval 0.11 to 0.66) and underlying conditions (0.15, 0.08 to 0.30). Vaccine effectiveness was 73% (95% confidence interval 34% to 89%). None of the eight vaccinated cases died. Preliminary evidence suggests some protection from the 2008-9 trivalent inactivated vaccine against pandemic influenza A/H1N1 2009, particularly severe forms of the disease, diagnosed in a specialty hospital during the influenza epidemic in Mexico City.

  8. Health-related behaviors and effectiveness of trivalent inactivated versus live attenuated influenza vaccine in preventing influenza-like illness among young adults.

    Science.gov (United States)

    Woolpert, Tabitha; Phillips, Christopher J; Sevick, Carter; Crum-Cianflone, Nancy F; Blair, Patrick J; Faix, Dennis

    2014-01-01

    Vaccination is the preferred preventive strategy against influenza. Though health behaviors are known to affect immunity and vaccine delivery modes utilize different immune processes, data regarding the preferred influenza vaccine type among adults endorsing specific health-related behaviors (alcohol use, tobacco use, and exercise level) are limited. The relative effectiveness of two currently available influenza vaccines were compared for prevention of influenza-like illness during 2 well-matched influenza seasons (2006/2007, 2008/2009) among US military personnel aged 18-49 years. Relative vaccine effectiveness was compared between those self-reporting and not reporting recent smoking history and potential alcohol problem, and by exercise level using Cox proportional hazard modeling adjusted for sociodemographic and military factors, geographic area, and other health behaviors. 28,929 vaccination events and 3936 influenza-like illness events over both influenza seasons were studied. Of subjects, 27.5% were smokers, 7.7% had a potential alcohol-related problem, 10.5% reported minimal exercise, and 4.4% reported high exercise levels. Overall, the risk of influenza-like illness did not significantly differ between live attenuated and trivalent inactivated influenza vaccine recipients (hazard ratio, 0.98; 95% confidence interval, 0.90-1.06). In the final adjusted model, the relative effectiveness of the 2 vaccine types did not differ by smoking status (p = 0.10), alcohol status (p = 0.21), or activity level (p = 0.11). Live attenuated and trivalent inactivated influenza vaccines were similarly effective in preventing influenza-like illness among young adults and did not differ by health-related behavior status. Influenza vaccine efforts should continue to focus simply on delivering vaccine.

  9. Immunogenicity and safety of a quadrivalent inactivated influenza vaccine compared with two trivalent inactivated influenza vaccines containing alternate B strains in adults: A phase 3, randomized noninferiority study.

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    Treanor, John T; Albano, Frank R; Sawlwin, Daphne C; Graves Jones, Alison; Airey, Jolanta; Formica, Neil; Matassa, Vince; Leong, Jane

    2017-04-04

    Vaccination is the most effective means of influenza prevention. Efficacy of trivalent vaccines may be enhanced by including both B strain lineages. This phase 3, double-blind study assessed the immunogenicity and safety/tolerability of a quadrivalent inactivated influenza vaccine (IIV4) versus the United States (US)-licensed 2014-2015 trivalent inactivated influenza vaccine (IIV3-Yamagata [IIV3-YAM]; Afluria) and IIV3 containing the alternate Victoria B strain (IIV3-VIC) in adults ≥18years. Participants (n=3484) were randomized 2:1:1 and stratified by age to receive IIV4 (n=1741), IIV3-YAM (n=871), or IIV3-VIC (n=872). The primary objective was to demonstrate noninferiority of the immunological response to IIV4 versus IIV3-YAM and IIV3-VIC. Noninferiority was assessed by hemagglutination inhibition geometric mean titer (GMT) ratio (IIV3/IIV4; upper bound of two-sided 95% confidence interval [CI]≤1.5) and seroconversion rate (SCR) difference (IIV3 - IIV4; upper bound of two-sided 95% CI≤10%) for vaccine strains. Solicited local and systemic adverse events (AEs) were assessed for 7days postvaccination, AEs recorded for 28days postvaccination, and serious AEs for 6months postvaccination. IIV4 elicited a noninferior immune response for matched strains, and superior response for unmatched B strains not contained in IIV3 comparators. Adjusted GMT ratios (95% CI) for A/H1N1, A/H3N2, B/YAM, and B/VIC strains were 0.93 (0.88, 0.99), 0.93 (0.88, 0.98), 0.87 (IIV3-YAM; 0.82, 0.93), and 0.95 (IIV3-VIC; 0.88, 1.03), respectively. Corresponding values for SCR differences (95% CI) were -1.1 (-4.5, 2.3), -1.7 (-5.0, 1.7), -3.2 (IIV3-YAM; -7.4, 0.9), and -1.6 (IIV3-VIC; -5.8, 2.5). AEs were generally mild and experienced by 52.9% of participants. Serious AEs were reported with a slightly higher frequency with IIV4 (2.3%) versus IIV3-YAM (1.6%) and IIV3-VIC (1.5%). IIV4 demonstrated immunological noninferiority to the US-licensed IIV3, and superiority for unmatched B strains

  10. Randomized controlled ferret study to assess the direct impact of 2008-09 trivalent inactivated influenza vaccine on A(H1N1)pdm09 disease risk

    NARCIS (Netherlands)

    D.M. Skowronski (Danuta); M.E. Hamelin (Marie Ève); G. de Serres (Gaston); N.Z. Janjua (Naveed); G. Li (Guiyun); S. Sabaiduc (Suzana); X. Bouhy (Xavier); C. Couture (Christian); A. Leung (Anders); D. Kobasa (Darwyn); C. Embury-Hyatt (Carissa); E.I. de Bruin (Esther); R. Balshaw (Robert); S. Lavigne (Sophie); M. Petric (Martin); M.P.G. Koopmans D.V.M. (Marion); G. Boivin (Guy)

    2014-01-01

    textabstractDuring spring-summer 2009, several observational studies from Canada showed increased risk of medically-attended, laboratory-confirmed A(H1N1)pdm09 illness among prior recipients of 2008-09 trivalent inactivated influenza vaccine (TIV). Explanatory hypotheses included direct and indirect

  11. Uptake and Effectiveness of a Trivalent Inactivated Influenza Vaccine in Children in Urban and Rural Kenya, 2010 to 2012.

    Science.gov (United States)

    Katz, Mark A; Lebo, Emmaculate; Emukule, Gideon O; Otieno, Nancy; Caselton, Deborah L; Bigogo, Godfrey; Njuguna, Henry; Muthoka, Philip M; Waiboci, Lilian W; Widdowson, Marc-Alain; Xu, Xiyan; Njenga, Moses K; Mott, Joshua A; Breiman, Robert F

    2016-03-01

    In Africa, recent surveillance has demonstrated a high burden of influenza, but influenza vaccine is rarely used. In Kenya, a country with a tropical climate, influenza has been shown to circulate year-round, like in other tropical countries. During 3 months in 2010 and 2011 and 2 months in 2012, the Kenya Medical Research Institute/Centers for Disease Control and Prevention-Kenya offered free injectable trivalent inactivated influenza vaccine to children 6 months to 10 years old in 2 resource-poor communities in Kenya-Kibera and Lwak (total population ~50,000). We conducted a case-control study to evaluate vaccine effectiveness (VE) in preventing laboratory-confirmed influenza associated with influenza-like illness and acute lower respiratory illness. Of the approximately 18,000 eligible children, 41%, 48% and 51% received at least 1 vaccine in 2010, 2011 and 2012, respectively; 30%, 36% and 38% were fully vaccinated. VE among fully vaccinated children was 57% [95% confidence interval (CI): 29% to 74%] during a 6-month follow-up period, 39% (95% CI: 17% to 56%) during a 9-month follow-up period and 48% (95% CI: 32% to 61%) during a 12-month follow-up period. For the 12-month follow-up period, VE was statistically significant in children Kenya, parents of nearly half of the eligible children <10 years old chose to get their children vaccinated with a free influenza vaccine. During a 12-month follow-up period, the vaccine was moderately effective in preventing medically attended influenza-associated respiratory illness.

  12. Immunogenicity and safety of an inactivated trivalent split influenza virus vaccine in young children with recurrent wheezing.

    Science.gov (United States)

    Bae, E Young; Choi, Ui Yoon; Kwon, Hyo Jin; Jeong, Dae Chul; Rhim, Jung Woo; Ma, Sang Hyuk; Lee, Kyung Il; Kang, Jin Han

    2013-06-01

    Influenza virus vaccination is recommended for children, but so far, active vaccination has not been achieved because most parents lack knowledge of vaccine safety and many doctors are reluctant to administer vaccine due to concerns that steroids might alter immunogenicity. The aim of this study was to compare the immunogenicity and safety of inactivated trivalent split influenza virus vaccine between children with recurrent wheezing and healthy children of the same age group. Sixty-eight healthy children and 62 children with recurrent wheezing took part in this study. Seroconversion rates, seroprotection rates, geometric mean titers (GMTs), and geometric mean titer ratios (GMTRs) were measured by a hemagglutination inhibition assay for the assessment of immunogenicity. Solicited and unsolicited local and systemic adverse events were measured for the assessment of safety. Regarding immunogenicity, the seroconversion and seroprotection rates showed no difference overall between healthy children and children with recurrent wheezing. Also, no difference was observed between steroid-treated and nontreated groups with recurrent wheezing. Generally, the GMTs after vaccination were higher in the one-dose vaccination groups for healthy children and children with recurrent wheezing, but the GMTRs revealed different results according to strain in the two groups. Regarding safety, solicited local and systemic adverse events showed no differences between healthy children and children with recurrent wheezing. This study demonstrates that inactivated split influenza virus vaccine is able to induce protective immune responses in healthy children, as observed in previous studies, as well as in children with recurrent wheezing who require frequent steroid treatment.

  13. The effect of age and recent influenza vaccination history on the immunogenicity and efficacy of 2009-10 seasonal trivalent inactivated influenza vaccination in children.

    Directory of Open Access Journals (Sweden)

    Sophia Ng

    Full Text Available There is some evidence that annual vaccination of trivalent inactivated influenza vaccine (TIV may lead to reduced vaccine immunogenicity but evidence is lacking on whether vaccine efficacy is affected by prior vaccination history. The efficacy of one dose of TIV in children 6-8 y of age against influenza B is uncertain. We examined whether immunogenicity and efficacy of influenza vaccination in school-age children varied by age and past vaccination history.We conducted a randomized controlled trial of 2009-10 TIV. Influenza vaccination history in the two preceding years was recorded. Immunogenicity was assessed by comparison of HI titers before and one month after receipt of TIV/placebo. Subjects were followed up for 11 months with symptom diaries, and respiratory specimens were collected during acute respiratory illnesses to permit confirmation of influenza virus infections. We found that previous vaccination was associated with reduced antibody responses to TIV against seasonal A(H1N1 and A(H3N2 particularly in children 9-17 y of age, but increased antibody responses to the same lineage of influenza B virus in children 6-8 y of age. Serological responses to the influenza A vaccine viruses were high regardless of vaccination history. One dose of TIV appeared to be efficacious against confirmed influenza B in children 6-8 y of age regardless of vaccination history.Prior vaccination was associated with lower antibody titer rises following vaccination against seasonal influenza A vaccine viruses, but higher responses to influenza B among individuals primed with viruses from the same lineage in preceding years. In a year in which influenza B virus predominated, no impact of prior vaccination history was observed on vaccine efficacy against influenza B. The strains that circulated in the year of study did not allow us to study the effect of prior vaccination on vaccine efficacy against influenza A.

  14. [Effectiveness of Live Attenuated Influenza Vaccines and Trivalent Inactivated Influenza Vaccines against confirmed Influenza In Children and Adolescents in Saxony-Anhalt, 2012/13].

    Science.gov (United States)

    Hermann, N

    2015-07-01

    Since 2012, there are not only trivalent inactivated influenza vaccines (TIV) but also live attenuated influenza vaccines (LAIV) available for children aged 2-17 years in Germany. The Saxony-Anhalt State Office for Consumer Protection conducted a test-negative case-control-study. The aim of the study was to identify the effectiveness of LAIV and TIV against a confirmed influenza diagnosis in children and adolescents in Saxony-Anhalt in the season 2012/13. The children had nasal swabs taken, which were further diagnosed in a laboratory using the PCR method. 834 patients of 15 voluntarily participating paediatric surgeries in Saxony-Anhalt were analysed by multivariate logistic regression with STATA 12. Controlling for age group, gender and month of the disease's onset showed an effectiveness of all vaccines amongst the 2-17 years old (38% with 95% CI: 0.8-61%; p=0.046). A differentiation according to LAIV and TIV demonstrated a significant effectiveness for LAIV (84%) in children of all ages (95% CI: 45-95%, p=0.004). After stratification for age groups LAIV was proven efficient in children aged 2-6 years (90% with 95% CI: 20-99%, p=0.03), whilst it led to a non-significant result in children aged 7-17 years (74% with 95% CI: -32-95%, p=0.106). There was no significant effectiveness of TIV seen in any age group.The Saxony-Anhalt State Office for Consumer Protection endorses the use of LAIV in children in accordance with the STIKO recommendations, as long as no contraindication is evident. © Georg Thieme Verlag KG Stuttgart · New York.

  15. Safety of a Trivalent Inactivated Influenza Vaccine in Health Care Workers in Kurdistan Province, Western Iran; A Longitudinal Follow-up Study.

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    Soltani, Jafar; Jamil Amjadi, Mohamad

    2014-03-01

    We studied the safety of a trivalent inactivated surface antigen (split virion, inactivated) influenza vaccine, Begrivac® (Novartis Company), widely used in health care workers in Kurdistan. A longitudinal follow-up study was performed in Sanandaj city, west of Iran, recruiting 936 people. A questionnaire was completed for each participant, and all symptoms or abnormal physical findings were recorded. In part 1 of the study, the post-vaccination complaints were headache (5.3%), fever (7.9%), weakness (9.6%), chills (10.1%), sweating (10.5%), arthralgia (20.2%), and malaise (21.5%). Swelling of the injection site was seen in 267 (30.3%) participants, and pruritus of the injection site was seen in 290 (32.9%) participants. Redness and induration were also reported in 42.5% of the participants. Local reactions were mainly mild and lasted for 1-2 days. No systemic reactions were reported in the second part of the study. None of the participants experienced any inconvenience. We concluded that local adverse reactions after the trivalent inactivated split influenza vaccine, Begrivac®, in health care workers were far more common than expected. Continuous surveillance is needed to assess the potential risks and benefits of newly produced influenza vaccines.

  16. Randomized safety and immunogenicity trial of a seasonal trivalent inactivated split virion influenza vaccine (IVACFLU-S) in healthy young Vietnamese adults.

    Science.gov (United States)

    Anh, Dang Duc; Thiem, Vu Dinh; Anh, Nguyen Thi Hien; Huong, Vu Minh; Nga, Nguyen Tuyet; Thang, Tran Cong; Thai, Duong Huu; Chien, Vien Chinh; Holt, Renee; Wahid, Rahnuma; Flores, Jorge; Berlanda Scorza, Francesco; Taylor, David N

    2016-10-26

    Under the auspices of the World Health Organization (WHO) Global Action Plan, PATH supported evaluation of a trivalent, seasonal inactivated influenza vaccine candidate produced by the Institute of Vaccines and Medical Biologicals (IVAC), a Vietnamese manufacturer. In 2015, 60 healthy adult subjects 18-45years of age were enrolled in a Phase 1, single center, double blind, randomized, placebo-controlled study conducted at a district health center in Thai Binh Province, Vietnam. The study evaluated the overall safety and immunogenicity of a seasonal, trivalent inactivated split virion influenza vaccine. Volunteers were given either vaccine or placebo in a randomized 1:1 ratio. After undergoing screening, eligible volunteers provided their signed consent and were enrolled in the study. On the first day of immunization, randomly chosen volunteers received IVACFLU-S 15μg (mcg) hemagglutinin of each of the three strains in 0.5mL or placebo by intramuscular injection. All volunteers were monitored for adverse events and underwent blood testing at screening and Day 8 to assess the vaccine candidate's safety. Sera obtained before and 21days after immunization were tested for influenza antibody titers using the hemagglutination-inhibition (HAI) and microneutralization tests (MNT). Vaccine was well tolerated, and there were no serious adverse events reported. HAI and MNT identified serum antibody responses against the three influenza strains in nearly all volunteers who received the vaccine. Overall, serum HAI responses of fourfold or greater were observed in 93 percent, 83 percent, and 77 percent of H1, H3, and B strains, respectively. Seroprotection rates were also very high. IVAC's seasonal, trivalent influenza vaccine was safe and well tolerated and induced high levels of seroconversion and seroprotection rates. These clinical data are a first step towards demonstrating the feasibility of producing the vaccine locally and that seasonal vaccine production in Vietnam may

  17. Possible Impact of Yearly Childhood Vaccination With Trivalent Inactivated Influenza Vaccine (TIV) on the Immune Response to the Pandemic Strain H1N1.

    Science.gov (United States)

    Amer, Ahdi; Fischer, Howard; Li, Xiaoming; Asmar, Basim

    2016-03-01

    Annual vaccination of children against seasonal influenza with trivalent inactivated influenza vaccine (TIV) has shown to be beneficial. However, this yearly practice may have unintended effect. Studies have shown that infection with wild type influenza A viruses can stimulate protective heterotypic immunity against unrelated or new influenza subtypes. We hypothesized that a consequence of yearly TIV vaccination is lack of induction of heterotypic immunity against the recent H1N1 pandemic. This was a retrospective case-control study. We reviewed the medical records of polymerase chain reaction-confirmed cases of 2009 H1N1 influenza infection in children 6 months to 18 years and a matched control group seen during the pandemic. We identified 353 polymerase chain reaction-confirmed H1N1 cases and 396 matching control subjects. Among the H1N1 group, 202/353 (57%) cases received a total of 477 doses of seasonal TIV compared with 218/396 (55%) in the control group who received a total of 435 doses. Seasonal TIV uptake was significantly higher in the H1N1 group 477/548 (87%) than in the control group, 435/532 (81%) (P = .017). Seasonal TIV uptake was significantly higher in H1N1-infected group. The finding suggests that the practice of yearly vaccination with TIV might have negatively affected the immune response against the novel pandemic H1N1 strain. Given the rarity of pandemic novel influenza viruses, and the high predictability of seasonal influenza occurrence, the practice of yearly influenza vaccination should be continued. However, the use of live attenuated intranasal vaccine, as opposed to TIV, may allow for the desirable development of a vigorous heterotypic immune response against future pandemics. © The Author(s) 2015.

  18. Immunogenicity and safety assessment of a trivalent, inactivated split influenza vaccine in Korean children: Double-blind, randomized, active-controlled multicenter phase III clinical trial.

    Science.gov (United States)

    Han, Seung Beom; Rhim, Jung-Woo; Shin, Hye Jo; Lee, Soo Young; Kim, Hyun-Hee; Kim, Jong-Hyun; Lee, Kyung-Yil; Ma, Sang Hyuk; Park, Joon Soo; Kim, Hwang Min; Kim, Chun Soo; Kim, Dong Ho; Choi, Young Youn; Cha, Sung-Ho; Hong, Young Jin; Kang, Jin Han

    2015-01-01

    A multicenter, double-blind, randomized, active-control phase III clinical trial was performed to assess the immunogenicity and safety of a trivalent, inactivated split influenza vaccine. Korean children between the ages of 6 months and 18 y were enrolled and randomized into a study (study vaccine) or a control vaccine group (commercially available trivalent, inactivated split influenza vaccine) in a 5:1 ratio. Antibody responses were determined using hemagglutination inhibition assay, and post-vaccination immunogenicity was assessed based on seroconversion and seroprotection rates. For safety assessment, solicited local and systemic adverse events up to 28 d after vaccination and unsolicited adverse events up to 6 months after vaccination were evaluated. Immunogenicity was assessed in 337 and 68 children of the study and control groups. In the study vaccine group, seroconversion rates against influenza A/H1N1, A/H3N2, and B strains were 62.0% (95% CI: 56.8-67.2), 53.4% (95% CI: 48.1-58.7), and 54.9% (95% CI: 48.1-60.2), respectively. The corresponding seroprotection rates were 95.0% (95% CI: 92.6-97.3), 93.8% (95% CI: 91.2-96.4), and 95.3% (95% CI: 93.0-97.5). The lower 95% CI limits of the seroconversion and seroprotection rates were over 40% and 70%, respectively, against all strains. Seroconversion and seroprotection rates were not significantly different between the study and control vaccine groups. Furthermore, the frequencies of adverse events were not significantly different between the 2 vaccine groups, and no serious vaccination-related adverse events were noted. In conclusion, the study vaccine exhibited substantial immunogenicity and safety in Korean children and is expected to be clinically effective.

  19. Randomized trial to compare the safety and immunogenicity of CSL Limited's 2009 trivalent inactivated influenza vaccine to an established vaccine in United States children.

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    Brady, Rebecca C; Hu, Wilson; Houchin, Vonda G; Eder, Frank S; Jackson, Kenneth C; Hartel, Gunter F; Sawlwin, Daphne C; Albano, Frank R; Greenberg, Michael

    2014-12-12

    A trivalent inactivated influenza vaccine (CSL's TIV, CSL Limited) was licensed under USA accelerated approval regulations for use in persons≥18 years. We performed a randomized, observer-blind study to assess the safety and immunogenicity of CSL's TIV versus an established US-licensed vaccine in a population≥6 months to vaccination history determined the dosing regimen (one or two vaccinations). Subjects received CSL's TIV (n=739) or the established vaccine (n=735) in the autumn of 2009. Serum hemagglutination-inhibition titers were determined pre-vaccination and 30 days after the last vaccination. No febrile seizures or other vaccine-related SAEs were reported. After the first vaccination for Cohorts A and B, respectively, the relative risks of fever were 2.73 and 2.32 times higher for CSL's TIV compared to the established vaccine. Irritability and loss of appetite (for Cohort A) and malaise (for Cohort B) were also significantly higher for CSL's TIV compared to the established vaccine. Post-vaccination geometric mean titers (GMTs) for CSL's TIV versus the established vaccine were 385.49 vs. 382.45 for H1N1; 669.13 vs. 705.61 for H3N2; and 100.65 vs. 93.72 for B. CSL's TIV demonstrated immunological non-inferiority to the established vaccine in all cohorts. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Uptake and Effectiveness of a Trivalent Inactivated Influenza Vaccine in Children in Urban and Rural Kenya, 2010 to 2012

    NARCIS (Netherlands)

    Katz, M.A.; Lebo, E.; Emukule, G.O.; Otieno, N.; Caselton, D.L.; Bigogo, G.; Njuguna, H.; Muthoka, P.M.; Waiboci, L.W.; Widdowson, M.A.; Xu, X.; Njenga, M.K.; Mott, J.A.; Breiman, R.F.

    2016-01-01

    BACKGROUND: In Africa, recent surveillance has demonstrated a high burden of influenza, but influenza vaccine is rarely used. In Kenya, a country with a tropical climate, influenza has been shown to circulate year-round, like in other tropical countries. METHODS: During 3 months in 2010 and 2011 and

  1. Safety and tolerability of a cell culture derived trivalent subunit inactivated influenza vaccine administered to healthy children and adolescents: A Phase III, randomized, multicenter, observer-blind study.

    Science.gov (United States)

    Nolan, Terry; Chotpitayasunondh, Tawee; Capeding, Maria Rosario; Carson, Simon; Senders, Shelly David; Jaehnig, Peter; de Rooij, Richard; Chandra, Richa

    2016-01-04

    Cell culture-derived inactivated influenza vaccines (TIVc) are necessary for scale and predictability of production to meet global demand. This study compared the safety and tolerability of TIVc with an egg-derived trivalent influenza vaccine (TIVf) in 4-17 yearolds. A Phase 3 observer blind, multicenter study enrolled 2055 healthy participants randomized 2:1 to receive either TIVc or TIVf, respectively (1372 TIVc and 683 TIVf evaluable subjects). Participants received one dose each on Days 1 and 28 (4-8 year-olds not previously vaccinated [NPV]) or one dose on Day 1 (4-8 and 9-17 yearolds previously vaccinated [PV]). Solicited adverse events (AEs) occurring within 7 days after each vaccination were assessed; participants were followed up for 6 months after their last dose for safety. Most solicited and unsolicited AEs were mild to moderate with vaccine-related SAEs were reported. TIVc and TIVf were similar in percentages of participants reporting solicited reactions in 4-8 years NPV group after the 1st dose: local reactions, TIVc: 48%, TIVf: 43%; systemic reactions, TIVc: 34%, TIVf: 32%; percentages were lower following the 2nd dose in TIVc; local reactions: TIVc: 40%; TIVf: 43%; systemic reactions: TIVc: 21%; TIVf: 22%. In 4-17 years PV group, solicited reactions were lower following TIVf, local reactions: TIVc: 53%; TIVf: 43%; systemic reactions: TIVc: 37%, TIVf: 30%. Injection-site pain was the most common solicited reaction, and was similar following TIVc and TIVf in 4-8 yearolds (TIVc: 56%; TIVf: 55%), and lower following TIVf in 9-17 years group (TIVc: 52%; TIVf: 42%). Reporting of unsolicited AEs was similar for TIVc and TIVf across the two age groups. TIVc was well tolerated and had a safety and reactogenicity profile similar to that of TIVf in healthy 4-17 yearolds (NCT01857206). Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  2. Effectiveness of the 2012/13 trivalent live and inactivated influenza vaccines in children and adolescents in Saxony-Anhalt, Germany: a test-negative case-control study.

    Directory of Open Access Journals (Sweden)

    Carina Helmeke

    Full Text Available A live attenuated influenza vaccine has been available in Germany since the influenza season 2012/13, which is approved for children aged 2-17 years. Using data from our laboratory-based surveillance system, we described the circulation of influenza and non-influenza respiratory viruses during the influenza season 2012/13 in Saxony-Anhalt. We estimated the effectiveness of live and inactivated trivalent influenza vaccines in preventing laboratory-confirmed cases among children and adolescents. From week 40/2012 to 19/2013, sentinel paediatricians systematically swabbed acute respiratory illness patients for testing of influenza and 5 non-influenza viruses by PCR. We compared influenza cases and influenza-negative controls. Among children aged 2-17 years, we calculated overall and vaccine type-specific effectiveness against laboratory-confirmed influenza, stratified by age group (2-6; 7-17 years. We used multivariable logistic regression to adjust estimates for age group, sex and month of illness. Out of 1,307 specimens, 647 (35% were positive for influenza viruses and 189 (15% for at least one of the tested non-influenza viruses. For vaccine effectiveness estimation, we included 834 patients (mean age 7.3 years, 53% males in our analysis. Of 347 (42% influenza-positive specimens, 61 (18% were positive for A(H1N1pdm09, 112 (32% for A(H3N2 and 174 (50% for influenza B virus. The adjusted overall vaccine effectiveness including both age groups was 38% (95% CI: 0.8-61%. The adjusted effectiveness for inactivated vaccines was 37% (95% CI: -35-70% and for live vaccines 84% (95% CI: 45-95%. Effectiveness for the live vaccine was higher in 2-6 year-old children (90%, 95% CI: 20-99% than in children aged 7-17 years (74%, 95% CI: -32-95%. Our study of the strong influenza season in 2012/13 suggests a high preventive effect of live attenuated influenza vaccine especially among young children, which could not be reached by inactivated vaccines. We recommend

  3. Effectiveness of the 2012/13 trivalent live and inactivated influenza vaccines in children and adolescents in Saxony-Anhalt, Germany: a test-negative case-control study.

    Science.gov (United States)

    Helmeke, Carina; Gräfe, Lutz; Irmscher, Hanns-Martin; Gottschalk, Constanze; Karagiannis, Ioannis; Oppermann, Hanna

    2015-01-01

    A live attenuated influenza vaccine has been available in Germany since the influenza season 2012/13, which is approved for children aged 2-17 years. Using data from our laboratory-based surveillance system, we described the circulation of influenza and non-influenza respiratory viruses during the influenza season 2012/13 in Saxony-Anhalt. We estimated the effectiveness of live and inactivated trivalent influenza vaccines in preventing laboratory-confirmed cases among children and adolescents. From week 40/2012 to 19/2013, sentinel paediatricians systematically swabbed acute respiratory illness patients for testing of influenza and 5 non-influenza viruses by PCR. We compared influenza cases and influenza-negative controls. Among children aged 2-17 years, we calculated overall and vaccine type-specific effectiveness against laboratory-confirmed influenza, stratified by age group (2-6; 7-17 years). We used multivariable logistic regression to adjust estimates for age group, sex and month of illness. Out of 1,307 specimens, 647 (35%) were positive for influenza viruses and 189 (15%) for at least one of the tested non-influenza viruses. For vaccine effectiveness estimation, we included 834 patients (mean age 7.3 years, 53% males) in our analysis. Of 347 (42%) influenza-positive specimens, 61 (18%) were positive for A(H1N1)pdm09, 112 (32%) for A(H3N2) and 174 (50%) for influenza B virus. The adjusted overall vaccine effectiveness including both age groups was 38% (95% CI: 0.8-61%). The adjusted effectiveness for inactivated vaccines was 37% (95% CI: -35-70%) and for live vaccines 84% (95% CI: 45-95%). Effectiveness for the live vaccine was higher in 2-6 year-old children (90%, 95% CI: 20-99%) than in children aged 7-17 years (74%, 95% CI: -32-95%). Our study of the strong influenza season in 2012/13 suggests a high preventive effect of live attenuated influenza vaccine especially among young children, which could not be reached by inactivated vaccines. We recommend the

  4. Signal identification and evaluation for risk of febrile seizures in children following trivalent inactivated influenza vaccine in the Vaccine Safety Datalink Project, 2010-2011.

    Science.gov (United States)

    Tse, Alison; Tseng, Hung Fu; Greene, Sharon K; Vellozzi, Claudia; Lee, Grace M

    2012-03-02

    In fall 2010 in the southern hemisphere, an increased risk of febrile seizures was noted in young children in Australia in the 24 h after receipt of trivalent inactivated influenza vaccine (TIV) manufactured by CSL Biotherapies. Although the CSL TIV vaccine was not recommended for use in young children in the US, during the 2010-2011 influenza season near real-time surveillance was conducted for febrile seizures in the 0-1 days following first dose TIV in a cohort of 206,174 vaccinated children ages 6 through 59 months in the Vaccine Safety Datalink Project. On a weekly basis, surveillance was conducted with the primary approach of a self-controlled risk interval design and the secondary approach of a current vs. historical vaccinee design. Sequential statistical methods were employed to account for repeated analyses of accumulating data. Signals for seizures based on computerized data were identified in mid November 2010 using a current vs. historical design and in late December 2010 using a self-controlled risk interval design. Further signal evaluation was conducted with chart-confirmed febrile seizure cases using only data from the primary approach (i.e. self-controlled risk interval design). The magnitude of the incidence rate ratio and risk difference comparing risk of seizures in the 0-1 days vs. 14-20 days following TIV differed by receipt of concomitant 13-valent pneumococcal conjugate vaccine (PCV13). Among children 6-59 months of age, the incidence rate ratio (IRR) for TIV adjusted for concomitant PCV13 was 2.4 (95% CI 1.2, 4.7) while the IRR for PCV13 adjusted for concomitant TIV was 2.5 (95% CI 1.3, 4.7). The IRR for concomitant TIV and PCV13 was 5.9 (95% CI 3.1, 11.3). Risk difference estimates varied by age due to the varying baseline risk for seizures in young children, with the highest estimates occurring at 16 months (12.5 per 100,000 doses for TIV without concomitant PCV13, 13.7 per 100,000 doses for PCV13 without concomitant TIV, and 44.9 per

  5. Effectiveness of seasonal trivalent inactivated influenza vaccine in preventing influenza hospitalisations and primary care visits in Auckland, New Zealand, in 2013.

    Science.gov (United States)

    Turner, N; Pierse, N; Bissielo, A; Huang, Qs; Radke, S; Baker, Mg; Widdowson, Ma; Kelly, H

    2014-08-28

    This study reports the first vaccine effectiveness (VE) estimates for the prevention of general practice visits and hospitalisations for laboratory-confirmed influenza from an urban population in Auckland, New Zealand, in the same influenza season (2013). A case test-negative design was used to estimate propensity-adjusted VE in both hospital and community settings. Patients with a severe acute respiratory infection (SARI) or influenza-like illness (ILI) were defined as requiring hospitalisation (SARI) or attending a general practice (ILI) with a history of fever or measured temperature ≥38 °C, cough and onset within the past 10 days. Those who tested positive for influenza virus were cases while those who tested negative were controls. Results were analysed to 7 days post symptom onset and adjusted for the propensity to be vaccinated and the timing during the influenza season. Influenza vaccination provided 52% (95% CI: 32 to 66) protection against laboratory-confirmed influenza hospitalisation and 56% (95% CI: 34 to 70) against presenting to general practice with influenza. VE estimates were similar for all types and subtypes. This study found moderate effectiveness of influenza vaccine against medically attended and hospitalised influenza in New Zealand, a temperate, southern hemisphere country during the 2013 winter season.

  6. Immunogenicity and safety of high-dose trivalent inactivated influenza vaccine compared to standard-dose vaccine in children and young adults with cancer or HIV infection.

    Science.gov (United States)

    Hakim, Hana; Allison, Kim J; Van de Velde, Lee-Ann; Tang, Li; Sun, Yilun; Flynn, Patricia M; McCullers, Jonathan A

    2016-06-08

    Approaches to improve the immune response of immunocompromised patients to influenza vaccination are needed. Children and young adults (3-21 years) with cancer or HIV infection were randomized to receive 2 doses of high-dose (HD) trivalent influenza vaccine (TIV) or of standard-dose (SD) TIV. Hemagglutination inhibition (HAI) antibody titers were measured against H1, H3, and B antigens after each dose and 9 months later. Seroconversion was defined as ≥4-fold rise in HAI titer comparing pre- and post-vaccine sera. Seroprotection was defined as a post-vaccine HAI titer ≥1:40. Reactogenicity events (RE) were solicited using a structured questionnaire 7 and 14 days after each dose of vaccine, and adverse events by medical record review for 21 days after each dose of vaccine. Eighty-five participants were enrolled in the study; 27 with leukemia, 17 with solid tumor (ST), and 41 with HIV. Recipients of HD TIV had significantly greater fold increase in HAI titers to B antigen in leukemia group and to H1 antigen in ST group compared to SD TIV recipients. This increase was not documented in HIV group. There were no differences in seroconversion or seroprotection between HD TIV and SD TIV in all groups. There was no difference in the percentage of solicited RE in recipients of HD TIV (54% after dose 1 and 38% after dose 2) compared to SD TIV (40% after dose 1 and 20% after dose 2, p=0.27 and 0.09 after dose 1 and 2, respectively). HD TIV was more immunogenic than SD TIV in children and young adults with leukemia or ST, but not with HIV. HD TIV was safe and well-tolerated in children and young adults with leukemia, ST, or HIV. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Safety and immunogenicity of a high dosage trivalent influenza vaccine among elderly subjects

    NARCIS (Netherlands)

    Couch, Robert B.; Winokur, Patricia; Brady, Rebecca; Belshe, Robert; Chen, Wilbur H.; Cate, Thomas R.; Sigurdardottir, Bryndis; Hoeper, Amy; Graham, Irene L.; Edelman, Robert; He, Fenhua; Nino, Diane; Capellan, Jose; Ruben, Frederick L.

    2007-01-01

    To improve immune responses to influenza vaccine, a trivalent inactivated vaccine containing 60 mu g of the HA of each component (A/H3N2, A/H1N1, B) was compared to a licensed vaccine containing 15 mu g of the HA of each. More local and systemic reactions were reported by subjects given the high

  8. Review of 10 years of clinical experience with Chinese domestic trivalent influenza vaccine Anflu®.

    Science.gov (United States)

    Liu, Yan; Wu, Jun-Yu; Wang, Xu; Chen, Jiang-Ting; Xia, Ming; Hu, Wei; Zou, Yong; Yin, Wei-Dong

    2014-01-01

    Influenza viruses cause annual winter epidemics globally and influenza vaccination is most effective way to prevent the disease or severe outcomes from the illness, especially in developing countries. However, the majority of the world's total production capacity of influenza vaccine is concentrated in several large multinational manufacturers. A safe and effective preventive vaccine for the developing countries is urgent. Anflu®, a Chinese domestic preservative-free, split-virus trivalent influenza vaccine (TIV), was introduced by Sinovac Biotech Ltd. in 2006. Until now, 20.6 million doses worldwide of Anflu® were sold. Since 2003, 13 company-sponsored clinical studies investigating the immunogenicity and safety of Anflu® have been completed, in which 6642 subjects participated and were vaccinated by Anflu®. Anflu® was generally well tolerated in all age groups, and highly immunogenic in healthy adults and elderly and exceeded the licensure criteria in Europe. This review presents and discusses the experience with Anflu® during the past decade. A new Chinese domestic, preservative-free, unadjuvanted, inactivated split-virus trivalent influenza vaccine (TIV), Anflu®, was introduced into human clinical trials in 2003 and then licensed in China in 2006. The vaccine contains 15 µg/0.5 ml hemagglutinin from each of the 3 influenza virus strains (including an H1N1 influenza A virus subtype, an H3N2 influenza A virus subtype, and an influenza B virus) that are expected to be circulating in the up-coming influenza season. The clinical data pertaining to Anflu® will be reviewed and compared with other TIVs available at present.

  9. Seasonal Inactivated Influenza Virus Vaccines

    OpenAIRE

    Couch, Robert B.

    2008-01-01

    Inactivated influenza virus vaccines are the primary modality used for prevention of influenza. A system of annual identification of new strains causing illnesses, selections for vaccines, chick embryo growth, inactivation, processing, packaging, distribution and usage has been in place for decades. Current vaccines contain 15 µg of the HA of an A/H1N1, A/H3N2 and B strain and are given parenterally to induce serum anti-HA antibody for prevention of subsequent infection and illness from natur...

  10. Efficacy of trivalent influenza vaccine against laboratory-confirmed influenza among young children in a randomized trial in Bangladesh.

    Science.gov (United States)

    Rolfes, Melissa A; Goswami, Doli; Sharmeen, Amina Tahia; Yeasmin, Sultana; Parvin, Nasrin; Nahar, Kamrun; Rahman, Mustafizur; Barends, Marion; Ahmed, Dilruba; Rahman, Mohammed Ziaur; Bresee, Joseph; Luby, Stephen; Moulton, Lawrence H; Santosham, Mathuram; Fry, Alicia M; Brooks, W Abdullah

    2017-12-15

    Few trials have evaluated influenza vaccine efficacy (VE) in young children, a group particularly vulnerable to influenza complications. We aimed to estimate VE against influenza in children aged Children aged 6-23 months were enrolled 1:1 in a parallel, double-blind, randomized controlled trial of trivalent inactivated influenza vaccine (IIV3) versus inactivated polio vaccine (IPV); conducted August 2010-March 2014 in Dhaka, Bangladesh. Children received two pediatric doses of vaccine, one month apart, and were followed for one year for febrile and respiratory illness. Field assistants conducted weekly home-based, active surveillance and ill children were referred to the study clinic for clinical evaluation and nasopharyngeal wash specimen collection. Analysis included all children who received a first vaccine dose and compared yearly incidence of reverse transcription polymerase chain reaction (RT-PCR)-confirmed influenza between trial arms. The VE was estimated as 1-(rate ratio of illness) × 100%, using unadjusted Poisson regression. The trial was registered with ClinicalTrials.gov, number NCT01319955. Across four vaccination rounds, 4081 children were enrolled and randomized, contributing 2576 child-years of observation to the IIV3 arm and 2593 child-years to the IPV arm. Influenza incidence was 10 episodes/100 child-years in the IIV3 arm and 15 episodes/100 child-years in the IPV arm. Overall, the VE was 31% (95% confidence interval 18, 42%) against any RT-PCR-confirmed influenza. The VE varied by season, but was similar by influenza type/subtype and participant age and sex. Vaccination of young children with IIV3 provided a significant reduction in laboratory-confirmed influenza; however, exploration of additional influenza vaccine strategies, such as adjuvanted vaccines or standard adult vaccine doses, is warranted to find more effective influenza vaccines for young children in low-income countries. Published by Elsevier Ltd.

  11. Humoral antibody response after receipt of inactivated seasonal influenza vaccinations one year apart in children

    OpenAIRE

    Fang, VJ; Ip, DKM; Ng, S; Chiu, SS; Cowling, BJ; Leung, GM; Peiris, JSM

    2012-01-01

    Background: Annual vaccination against seasonal influenza viruses is recommended for school-age children in some countries. There are limited data on the immunogenicity and efficacy of repeated influenza vaccinations. Methods: In a randomized controlled trial, we administered seasonal trivalent inactivated influenza vaccine (TIV) or placebo to 64 children 6-15 years of age in two consecutive years and explored their humoral antibody responses. Results: Receipt of TIV in the first year was ass...

  12. A trivalent virus-like particle vaccine elicits protective immune responses against seasonal influenza strains in mice and ferrets.

    Directory of Open Access Journals (Sweden)

    Ted M Ross

    Full Text Available There is need for improved human influenza vaccines, particularly for older adults who are at greatest risk for severe disease, as well as to address the continuous antigenic drift within circulating human subtypes of influenza virus. We have engineered an influenza virus-like particle (VLP as a new generation vaccine candidate purified from the supernatants of Sf9 insect cells following infection by recombinant baculoviruses to express three influenza virus proteins, hemagglutinin (HA, neuraminidase (NA, and matrix 1 (M1. In this study, a seasonal trivalent VLP vaccine (TVV formulation, composed of influenza A H1N1 and H3N2 and influenza B VLPs, was evaluated in mice and ferrets for the ability to elicit antigen-specific immune responses. Animals vaccinated with the TVV formulation had hemagglutination-inhibition (HAI antibody titers against all three homologous influenza virus strains, as well as HAI antibodies against a panel of heterologous influenza viruses. HAI titers elicited by the TVV were statistically similar to HAI titers elicited in animals vaccinated with the corresponding monovalent VLP. Mice vaccinated with the TVV had higher level of influenza specific CD8+ T cell responses than a commercial trivalent inactivated vaccine (TIV. Ferrets vaccinated with the highest dose of the VLP vaccine and then challenged with the homologous H3N2 virus had the lowest titers of replicating virus in nasal washes and showed no signs of disease. Overall, a trivalent VLP vaccine elicits a broad array of immunity and can protect against influenza virus challenge.

  13. Microneedle delivery of trivalent influenza vaccine to the skin induces long-term cross-protection.

    Science.gov (United States)

    Kim, Yeu-Chun; Lee, Su-Hwa; Choi, Won-Hyung; Choi, Hyo-Jick; Goo, Tae-Won; Lee, Ju-Hie; Quan, Fu-Shi

    2016-12-01

    A painless self-immunization method with effective and broad cross-protection is urgently needed to prevent infections against newly emerging influenza viruses. In this study, we investigated the cross-protection efficacy of trivalent influenza vaccine containing inactivated A/PR/8/34 (H1N1), A/Hong Kong/68 (H3N2) and B/Lee/40 after skin vaccination using microneedle patches coated with this vaccine. Microneedle vaccination of mice in the skin provided 100% protection against lethal challenges with heterologous pandemic strain influenza A/California/04/09, heterogeneous A/Philippines/2/82 and B/Victoria/287 viruses 8 months after boost immunization. Cross-reactive serum IgG antibody responses against heterologous influenza viruses A/California/04/09, A/Philippines/2/82 and B/Victoria/287 were induced at high levels. Hemagglutination inhibition titers were also maintained at high levels against these heterogeneous viruses. Microneedle vaccination induced substantial levels of cross-reactive IgG antibody responses in the lung and cellular immune responses, as well as cross-reactive antibody-secreting plasma cells in the spleen. Viral loads in the lung were significantly (p microneedle array could provide protection against seasonal epidemic or new pandemic strain of influenza viruses.

  14. Antibody Responses with Fc-Mediated Functions after Vaccination of HIV-Infected Subjects with Trivalent Influenza Vaccine

    DEFF Research Database (Denmark)

    Kristensen, Anne B; Lay, William N; Ana-Sosa-Batiz, Fernanda

    2016-01-01

    This study seeks to assess the ability of seasonal trivalent inactivated influenza vaccine (TIV) to induce nonneutralizing antibodies (Abs) with Fc-mediated functions in HIV-uninfected and HIV-infected subjects. Functional influenza-specific Ab responses were studied in 30 HIV-negative and 27 HIV......-positive subjects immunized against seasonal influenza. All 57 subjects received the 2015 TIV. Fc-mediated antihemagglutinin (anti-HA) Ab activity was measured in plasma before and 4 weeks after vaccination using Fc-receptor-binding assays, NK cell activation assays, and phagocytosis assays. At baseline, the HIV......-positive group had detectable but reduced functional Ab responses to both vaccine and nonvaccine influenza antigens. TIV enhanced Fc-mediated Ab responses in both HIV-positive and HIV-negative groups. A larger rise was generally observed in the HIV-positive group, such that there was no difference in functional...

  15. Cost-effectiveness of quadrivalent versus trivalent influenza vaccine in the United States

    NARCIS (Netherlands)

    de Boer, Pieter; Pitman, R.J.; Macabeo, B.; Chit, A.; Postma, M.J.; Crépey, P.

    2014-01-01

    BACKGROUND: Currently used trivalent influenza vaccines (TIVs) contain two strains of influenza A and one strain of influenza B. However, co-circulation of two distinct B lineages and difficulties in predicting which lineage will predominate in the next season have led to frequent B-strain

  16. Titration of individual strains in trivalent live-attenuated influenza vaccine without neutralization.

    Science.gov (United States)

    Sirinonthanawech, Naraporn; Surichan, Somchaiya; Namsai, Aphinya; Puthavathana, Pilaipan; Auewarakul, Prasert; Kongchanagul, Alita

    2016-11-01

    Formulation and quality control of trivalent live-attenuated influenza vaccine requires titration of infectivity of individual strains in the trivalent mix. This is usually performed by selective neutralization of two of the three strains and titration of the un-neutralized strain in cell culture or embryonated eggs. This procedure requires standard sera with high neutralizing titer against each of the three strains. Obtaining standard sera, which can specifically neutralize only the corresponding strain of influenza viruses and is able to completely neutralize high concentration of virus in the vaccine samples, can be a problem for many vaccine manufacturers as vaccine stocks usually have very high viral titers and complete neutralization may not be obtained. Here an alternative approach for titration of individual strain in trivalent vaccine without the selective neutralization is presented. This was done by detecting individual strains with specific antibodies in an end-point titration of a trivalent vaccine in cell culture. Similar titers were observed in monovalent and trivalent vaccines for influenza A H3N2 and influenza B strains, whereas the influenza A H1N1 strain did not grow well in cell culture. Viral interference among the vaccine strains was not observed. Therefore, providing that vaccine strains grow well in cell culture, this assay can reliably determine the potency of individual strains in trivalent live-attenuated influenza vaccines. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Liposome-based cationic adjuvant CAF01 enhances the protection conferred by a commercial inactivated influenza vaccine in ferrets

    DEFF Research Database (Denmark)

    Martel, Cyril Jean-Marie; Agger, Else Marie; Jensen, Trine Hammer

    Objectives: To assess the effect of CAF01 adjuvant associated to a commercial trivalent inactivated influenza vaccine in the ferret model. Methods:  Ferrets were vaccinated with a range of doses of Sanofi-Pasteur's Vaxigrip with or without the CAF01 adjuvant, and challenged with either one of two H...

  18. Review of seasonal influenza in Canada: Burden of disease and the cost-effectiveness of quadrivalent inactivated influenza vaccines.

    Science.gov (United States)

    Thommes, Edward W; Kruse, Morgan; Kohli, Michele; Sharma, Rohita; Noorduyn, Stephen G

    2017-04-03

    In the 2015/16 influenza season, the Canadian National Advisory Committee on Immunization (NACI) recommended vaccination with quadrivalent inactivated influenza vaccine (QIV) for infants aged 6-23 months and trivalent inactivated influenza vaccines (TIVs) or QIVs in adults. The objective of this review (GSK study identifier: HO-13-14054) is to examine the epidemiology and disease burden of influenza in Canada and the economic benefits of vaccination. To inform this review, we performed a systematic literature search of relevant Canadian literature and National surveillance data. Influenza B viruses from phylogenetically-distinct lineages (B/Yamagata and B/Victoria) co-circulate in Canada, and are an important cause of influenza complications. Modeling studies, including those postdating the search suggest that switching from TIV to QIV in Canada reduces the burden of influenza and would likely be cost-effective. However, more robust real-world outcomes data is required to inform health policy decision makers on appropriate influenza vaccination strategies for Canada.

  19. Influenza Vaccination Strategies: Comparing Inactivated and Live Attenuated Influenza Vaccines

    Science.gov (United States)

    Sridhar, Saranya; Brokstad, Karl A.; Cox, Rebecca J.

    2015-01-01

    Influenza is a major respiratory pathogen causing annual outbreaks and occasional pandemics. Influenza vaccination is the major method of prophylaxis. Currently annual influenza vaccination is recommended for groups at high risk of complications from influenza infection such as pregnant women, young children, people with underlying disease and the elderly, along with occupational groups such a healthcare workers and farm workers. There are two main types of vaccines available: the parenteral inactivated influenza vaccine and the intranasal live attenuated influenza vaccine. The inactivated vaccines are licensed from 6 months of age and have been used for more than 50 years with a good safety profile. Inactivated vaccines are standardized according to the presence of the viral major surface glycoprotein hemagglutinin and protection is mediated by the induction of vaccine strain specific antibody responses. In contrast, the live attenuated vaccines are licensed in Europe for children from 2–17 years of age and provide a multifaceted immune response with local and systemic antibody and T cell responses but with no clear correlate of protection. Here we discuss the immunological immune responses elicited by the two vaccines and discuss future work to better define correlates of protection. PMID:26343192

  20. Cost-effectiveness of seasonal quadrivalent versus trivalent influenza vaccination in the United States: A dynamic transmission modeling approach.

    Science.gov (United States)

    Brogan, Anita J; Talbird, Sandra E; Davis, Ashley E; Thommes, Edward W; Meier, Genevieve

    2017-03-04

    Trivalent inactivated influenza vaccines (IIV3s) protect against 2 A strains and one B lineage; quadrivalent versions (IIV4s) protect against an additional B lineage. The objective was to assess projected health and economic outcomes associated with IIV4 versus IIV3 for preventing seasonal influenza in the US. A cost-effectiveness model was developed to interact with a dynamic transmission model. The transmission model tracked vaccination, influenza cases, infection-spreading interactions, and recovery over 10 y (2012-2022). The cost-effectiveness model estimated influenza-related complications, direct and indirect costs (2013-2014 US$), health outcomes, and cost-effectiveness. Inputs were taken from published/public sources or estimated using regression or calibration. Outcomes were discounted at 3% per year. Scenario analyses tested the reliability of the results. Seasonal vaccination with IIV4 versus IIV3 is predicted to reduce annual influenza cases by 1,973,849 (discounted; 2,325,644 undiscounted), resulting in 12-13% fewer cases and influenza-related complications and deaths. These reductions are predicted to translate into 18,485 more quality-adjusted life years (QALYs) accrued annually for IIV4 versus IIV3. Increased vaccine-related costs ($599 million; 5.7%) are predicted to be more than offset by reduced influenza treatment costs ($699 million; 12.2%), resulting in direct medical cost saving annually ($100 million; 0.6%). Including indirect costs, savings with IIV4 are predicted to be $7.1 billion (5.6%). Scenario analyses predict IIV4 to be cost-saving in all scenarios tested apart from low infectivity, where IIV4 is predicted to be cost-effective. In summary, seasonal influenza vaccination in the US with IIV4 versus IIV3 is predicted to improve health outcomes and reduce costs.

  1. [Antibody response to trivalent anti-influenza vaccination (inactivated virus) A/Texas/1/77 H3N2), A/URSS/90/77 (H1N1), B/Hong Kong/8/73].

    Science.gov (United States)

    Mancini, G; Andreoni, M; Arangio-Ruiz, G; Sarrecchia, C; Donatelli, I; Resta, S; Rozera, C; Sordillo, P; Rocchi, G

    1982-05-01

    Seventy-five young recruits received an intramuscular dose of anti-influenza virus vaccine containing 300 U.I. of A/Texas/1/77 (H3N2), A/URSS/90/77 (H1N1), B/Hong Kong/8/73 strains. Antibody responses were detected by HI and SRH tests: immunogenicity of the preparation was different for the individual vaccine strain in spite of the similar amount of antigenic content, and the immunity conferred by vaccine strains did not significantly extend to new influenza virus strains which prevailed in 1979/80 winter season with the exception for A/Brazil/11/78 (H1N1).

  2. Influenza B vaccine lineage selection-An optimized trivalent vaccine

    NARCIS (Netherlands)

    A. Mosterín Höpping (Ana); J.M. Fonville (Judith); C.A. Russell (Colin); S.L. James (Sarah ); D.J. Smith (Derek James)

    2016-01-01

    textabstractEpidemics of seasonal influenza viruses cause considerable morbidity and mortality each year. Various types and subtypes of influenza circulate in humans and evolve continuously such that individuals at risk of serious complications need to be vaccinated annually to keep protection up to

  3. Impact of influenza B lineage-level mismatch between trivalent seasonal influenza vaccines and circulating viruses, 1999-2012.

    Science.gov (United States)

    Heikkinen, Terho; Ikonen, Niina; Ziegler, Thedi

    2014-12-01

    Influenza B virus strains in trivalent influenza vaccines are frequently mismatched to the circulating B strains, but the population-level impact of such mismatches is unknown. We assessed the impact of vaccine mismatch on the epidemiology of influenza B during 12 recent seasonal outbreaks of influenza in Finland. We analyzed all available nationwide data on virologically confirmed influenza infections in all age groups in Finland between 1 July 1999 and 30 June 2012, with the exclusion of the pandemic season of 2009-2010. We derived data on influenza infections and the circulation of different lineages of B viruses during each season from the Infectious Diseases Register and the National Influenza Center, National Institute for Health and Welfare, Finland. A total of 34 788 cases of influenza were recorded. Influenza A accounted for 74.0% and influenza B for 26.0% of all typed viruses. Throughout the 12 seasons, we estimated that 41.7% (3750 of 8993) of all influenza B infections were caused by viruses representing the other genetic lineage than the one in the vaccine. Altogether, opposite-lineage influenza B viruses accounted for 10.8% of all influenza infections in the population, the proportion being highest (16.8%) in children aged 10-14 years and lowest (2.6%) in persons aged ≥70 years. The population-level impact of lineage-level mismatch between the vaccine and circulating strains of influenza B viruses is substantial, especially among children and adolescents. The results provide strong support for the inclusion of both influenza B lineages in seasonal influenza vaccines. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  4. Live Attenuated Versus Inactivated Influenza Vaccine in Hutterite Children: A Cluster Randomized Blinded Trial.

    Science.gov (United States)

    Loeb, Mark; Russell, Margaret L; Manning, Vanessa; Fonseca, Kevin; Earn, David J D; Horsman, Gregory; Chokani, Khami; Vooght, Mark; Babiuk, Lorne; Schwartz, Lisa; Neupane, Binod; Singh, Pardeep; Walter, Stephen D; Pullenayegum, Eleanor

    2016-11-01

    Whether vaccinating children with intranasal live attenuated influenza vaccine (LAIV) is more effective than inactivated influenza vaccine (IIV) in providing both direct protection in vaccinated persons and herd protection in unvaccinated persons is uncertain. Hutterite colonies, where members live in close-knit, small rural communities in which influenza virus infection regularly occurs, offer an opportunity to address this question. To determine whether vaccinating children and adolescents with LAIV provides better community protection than IIV. A cluster randomized blinded trial conducted between October 2012 and May 2015 over 3 influenza seasons. (ClinicalTrials.gov: NCT01653015). 52 Hutterite colonies in Alberta and Saskatchewan, Canada. 1186 Canadian children and adolescents aged 36 months to 15 years who received the study vaccine and 3425 community members who did not. Children were randomly assigned according to community in a blinded manner to receive standard dosing of either trivalent LAIV or trivalent IIV. The primary outcome was reverse transcriptase polymerase chain reaction-confirmed influenza A or B virus in all participants (vaccinated children and persons who did not receive the study vaccine). Mean vaccine coverage among children in the LAIV group was 76.9% versus 72.3% in the IIV group. Influenza virus infection occurred at a rate of 5.3% (295 of 5560 person-years) in the LAIV group versus 5.2% (304 of 5810 person-years) in the IIV group. The hazard ratio comparing LAIV with IIV for influenza A or B virus was 1.03 (95% CI, 0.85 to 1.24). The study was conducted in Hutterite communities, which may limit generalizability. Immunizing children with LAIV does not provide better community protection against influenza than IIV. The Canadian Institutes for Health Research.

  5. 21 CFR 610.11a - Inactivated influenza vaccine, general safety test.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Inactivated influenza vaccine, general safety test... Inactivated influenza vaccine, general safety test. For inactivated influenza vaccine, the general safety test... subcutaneous or intraperitoneal injection of 5.0 milliliters of inactivated influenza vaccine into each guinea...

  6. Cost-effectiveness of inactivated seasonal influenza vaccination in a cohort of Thai children ≤60 months of age

    Science.gov (United States)

    Suntarattiwong, Piyarat; Ditsungnoen, Darunee; Pallas, Sarah E.; Abimbola, Taiwo O.; Klungthong, Chonticha; Fernandez, Stefan; Srisarang, Suchada; Chotpitayasunondh, Tawee; Dawood, Fatimah S.; Olsen, Sonja J.; Lindblade, Kim A.

    2017-01-01

    Background Vaccination is the best measure to prevent influenza. We conducted a cost-effectiveness evaluation of trivalent inactivated seasonal influenza vaccination, compared to no vaccination, in children ≤60 months of age participating in a prospective cohort study in Bangkok, Thailand. Methods A static decision tree model was constructed to simulate the population of children in the cohort. Proportions of children with laboratory-confirmed influenza were derived from children followed weekly. The societal perspective and one-year analytic horizon were used for each influenza season; the model was repeated for three influenza seasons (2012–2014). Direct and indirect costs associated with influenza illness were collected and summed. Cost of the trivalent inactivated seasonal influenza vaccine (IIV3) including promotion, administration, and supervision cost was added for children who were vaccinated. Quality-adjusted life years (QALY), derived from literature, were used to quantify health outcomes. The incremental cost-effectiveness ratio (ICER) was calculated as the difference in the expected total costs between the vaccinated and unvaccinated groups divided by the difference in QALYs for both groups. Results Compared to no vaccination, IIV3 vaccination among children ≤60 months in our cohort was not cost-effective in the introductory year (2012 season; 24,450 USD/QALY gained), highly cost-effective in the 2013 season (554 USD/QALY gained), and cost-effective in the 2014 season (16,200 USD/QALY gained). Conclusion The cost-effectiveness of IIV3 vaccination among children participating in the cohort study varied by influenza season, with vaccine cost and proportion of high-risk children demonstrating the greatest influence in sensitivity analyses. Vaccinating children against influenza can be economically favorable depending on the maturity of the program, influenza vaccine performance, and target population. PMID:28837594

  7. Prevalence of antibodies and humoral response after seasonal trivalent vaccination against influenza B lineages in an elderly population of Spain.

    Science.gov (United States)

    Muñoz, Ivan Sanz; Rello, Silvia Rojo; Lejarazu, Raúl Ortiz de

    2017-11-24

    The aim of this study was to analyze the presence of antibodies against both Yamagata and Victoria influenza B lineages and to check the response after seasonal trivalent vaccination. Haemagglutination inhibition assays were performed with pre-and post-vaccination serum samples from 174 individuals ≥65 years of age vaccinated with seasonal trivalent influenza vaccines during the 2006-2007, 2008-2009, 2009-2010 and 2010-2011 vaccine campaigns. 33.9% of individuals showed pre-vaccine protective antibodies (≥1/40) against B/Yamagata lineage and 41.4% against B/Victoria lineage. The annual trivalent vaccine induced significant homologous seroconversion in 14-35.6% of individuals in each vaccine campaign. The population ≥65 years has low-moderate seroprotection against B influenza lineages. Trivalent vaccination induced a slight increase of seroprotection. The trivalent vaccine should be administered to all individuals ≥65 years in all vaccine campaigns. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  8. The cost-effectiveness of trivalent and quadrivalent influenza vaccination in communities in South Africa, Vietnam and Australia

    NARCIS (Netherlands)

    de Boer, Pieter T.; Kelso, Joel K.; Haider, Nilimesh; Thi-Phuong-Lan Nguyen,; Moyes, Jocelyn; Cohen, Cheryl; Barr, Ian G.; Postma, Maarten J.; Milne, George J.

    2018-01-01

    provide better value for money than trivalent influenza vaccines (TIVs), we assessed the cost-effectiveness of TIV and QIV in low-and-middle income communities based in South Africa and Vietnam and contrasted these findings with those from a high-income community in Australia. Methods: Individual

  9. Cost-utility of quadrivalent versus trivalent influenza vaccine in Brazil – comparison of outcomes from different static model types

    Directory of Open Access Journals (Sweden)

    Laure-Anne Van Bellinghen

    2018-01-01

    Conclusion: All three models predicted a cost per quality-adjusted life year gained for quadrivalent versus trivalent influenza vaccine in the range of R$19,257 (FLORENCE to R$22,768 (FLORA with the best available data in Brazil (Appendix A.

  10. Influenza A haemagglutinin specific IgG responses in children and adults after seasonal trivalent live attenuated influenza vaccination.

    Science.gov (United States)

    Islam, Shahinul; Mohn, Kristin Greve-Isdahl; Krammer, Florian; Sanne, Mari; Bredholt, Geir; Jul-Larsen, Åsne; Tete, Sarah M; Zhou, Fan; Brokstad, Karl Albert; Cox, Rebecca Jane

    2017-10-09

    Influenza is a major respiratory pathogen and vaccination is the main method of prophylaxis. In 2012, the trivalent live attenuated influenza vaccine (LAIV3) was licensed in Europe for use in children. Vaccine-induced antibodies directed against the main viral surface glycoprotein, haemagglutinin (HA), play an important role in virus neutralization through different mechanism. The objective of this study was to dissect the HA specific antibody responses induced after LAIV3 immunization to the influenza A viruses in children and adults. Plasma was collected from 20 children and 20 adults pre- and post-LAIV3 vaccination (up to ayear) and analysed by the haemagglutination inhibition (HI) and ELISA assays. We found that LAIV3 boosted the HA specific IgG response against the head and the full-length of H3N2 in children, but not adults. Adults had higher levels of pre-existing stalk antibodies (towards H3N2 and H1N1), but these were not boosted by LAIV3. Importantly, we observed a trend in boosting of H1N1 HA stalk specific antibodies in children after LAIV3. Whereas, heterosubtypic H5 and H7 full-length HA specific antibodies were not boosted in either children or adults. In conclusion, LAIV3 elicited H3-head and low levels of H1 stalk specific antibody responses in children, supporting the prophylactic use of LAIV in children. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Trivalent influenza vaccine-induced antibody response to circulating influenza a (H3N2) viruses in 2010/11 and 2011/12 seasons.

    Science.gov (United States)

    Hiroi, Satoshi; Morikawa, Saeko; Nakata, Keiko; Maeda, Akiko; Kanno, Tsuneji; Irie, Shin; Ohfuji, Satoko; Hirota, Yoshio; Kase, Tetsuo

    2015-01-01

    To evaluate antibody response induced by trivalent inactivated influenza vaccine (TIV) against circulating influenza A (H3N2) strains in healthy adults during the 2010/11 and 2011/12 seasons, a hemagglutination-inhibition (HI) assay was utilized to calculate geometric mean antibody titer (GMT), seroprotection rate (post vaccination HI titers of ≥1 :40), and seroresponse rate (4-fold increase in antibody level). In the 2010/11 season, GMT increased 1.8- to 2.0-fold following the first dose of TIV against 3 circulating strains and 2.2-fold following the second compared to before vaccination. The seroresponse rate ranged from 22% to 26% following the first dose of TIV and from 31% to 33% following the second (n = 54 ). The seroprotection rate increased from a range of 6% to 13% to a range of 26% to 33% following the first dose of TIV and to a range of 37% to 42% following the second (n = 54 ). In the 2011/12 season, GMT increased 1.4-fold against A/Osaka/110/2011 and 1.8-fold against A/Osaka/5/2012. For A/Osaka/110/2011, the seroresponse rate was 29%, and the seroprotection rate increased from 26% to 55% following vaccination (n = 31 ). For A/Osaka/5/2012, the seroresponse rate was 26%, and the seroprotection rate increased from 68% to 84% following vaccination (n = 31 ). HI assays with reference antisera demonstrated that the strains in the 2011/12 season were antigenically distinct from vaccine strain (A/Victoria/210/2009). In conclusion, the vaccination increased the seroprotection rate against circulating H3N2 strains in the 2010/11 and 2011/12 seasons. Vaccination of TIV might have potential to induce reactive antibodies against antigenically distinct circulating H3N2 viruses.

  12. CAF01 potentiates immune responses and efficacy of an inactivated influenza vaccine in ferrets

    DEFF Research Database (Denmark)

    Martel, Cyril Jean-Marie; Agger, Else Marie; Poulsen, Julie Juul

    2011-01-01

    Trivalent inactivated vaccines (TIV) against influenza are given to 350 million people every year. Most of these are non-adjuvanted vaccines whose immunogenicity and protective efficacy are considered suboptimal. Commercially available non-adjuvanted TIV are known to elicit mainly a humoral immune...... response, whereas the induction of cell-mediated immune responses is negligible. Recently, a cationic liposomal adjuvant (dimethyldioctadecylammonium/trehalose 6,6'-dibehenate, CAF01) was developed. CAF01 has proven to enhance both humoral and cell-mediated immune responses to a number of different...... experimental vaccine candidates. In this study, we compared the immune responses in ferrets to a commercially available TIV with the responses to the same vaccine mixed with the CAF01 adjuvant. Two recently circulating H1N1 viruses were used as challenge to test the vaccine efficacy. CAF01 improved...

  13. Effectiveness of the live attenuated and the inactivated influenza vaccine in two-year-olds - a nationwide cohort study Finland, influenza season 2015/16.

    Science.gov (United States)

    Nohynek, Hanna; Baum, Ulrike; Syrjänen, Ritva; Ikonen, Niina; Sundman, Jonas; Jokinen, Jukka

    2016-09-22

    Although widely recommended, influenza vaccination of children is part of the national vaccination programme only in few countries. In addition to Canada and the United States (US), in Europe Finland and the United Kingdom have introduced live attenuated influenza vaccine (LAIV) for healthy children in their programmes. On 22 June 2016, the US Advisory Committee on Immunizations Practices, voted against further use of LAIV due to no observed vaccine effectiveness (VE) over three consecutive influenza seasons (2013/14 to 2015/16). We summarise the results of a nationwide, register-based cohort study (N=55,258 of whom 8,086 received LAIV and 4,297 TIV); all outcome (laboratory-confirmed influenza), exposure (vaccination) and confounding variable data were retrieved from four computerised national health registers, which were linked via a unique personal identity code assigned to all permanent Finnish residents regardless of nationality. Our study provides evidence of moderate effectiveness against any laboratory-confirmed influenza of the quadrivalent LAIV vaccine (VE: 51%; 95% confidence interval (CI): 28-66%) as well as the inactivated trivalent vaccine (VE: 61%; 95% CI: 31-78%) among two-year-olds during the influenza season 2015/16 in Finland. Based on these data, Finland will continue using LAIV for young children in its National Immunisation Programme this coming influenza season. This article is copyright of The Authors, 2016.

  14. Heterologous HA DNA vaccine prime--inactivated influenza vaccine boost is more effective than using DNA or inactivated vaccine alone in eliciting antibody responses against H1 or H3 serotype influenza viruses.

    Science.gov (United States)

    Wang, Shixia; Parker, Chris; Taaffe, Jessica; Solórzano, Alicia; García-Sastre, Adolfo; Lu, Shan

    2008-07-04

    The trivalent inactivated vaccine (TIV) is used to prevent seasonal influenza virus infection in humans, however, the immunogenicity of this vaccine may be influenced by the priming effect of previous influenza vaccinations or exposure to antigenically related influenza viruses. The current study examines the immunogenicity of a clinically licensed TIV in rabbits naïve to influenza antigens. Animals were immunized with either the licensed TIV, a bivalent (H1 and H3) HA DNA vaccine or the combination of both. Temporal and peak level serum anti-influenza virus IgG responses were determined by enzyme-linked immunosorbent assay (ELISA). Functional antibody responses were measured by hemagglutination inhibition and microneutralization against either A/NewCaledonia//20/99 (H1N1) or A/Panama/2007/99 (H3N2) influenza viruses. Our results demonstrate that the immunogenicity of the TIV is low in sero-negative animals. More significantly, the heterologous DNA prime-TIV boost regimen was more immunogenic than the homologous prime-boost using either TIV or DNA vaccines alone. This finding justifies further investigation of HA DNA vaccines as a priming immunogen for the next generation of vaccines against seasonal or pandemic influenza virus infections.

  15. CAF01 potentiates immune responses and efficacy of an inactivated influenza vaccine in ferrets.

    Directory of Open Access Journals (Sweden)

    Cyril Jean-Marie Martel

    Full Text Available Trivalent inactivated vaccines (TIV against influenza are given to 350 million people every year. Most of these are non-adjuvanted vaccines whose immunogenicity and protective efficacy are considered suboptimal. Commercially available non-adjuvanted TIV are known to elicit mainly a humoral immune response, whereas the induction of cell-mediated immune responses is negligible. Recently, a cationic liposomal adjuvant (dimethyldioctadecylammonium/trehalose 6,6'-dibehenate, CAF01 was developed. CAF01 has proven to enhance both humoral and cell-mediated immune responses to a number of different experimental vaccine candidates. In this study, we compared the immune responses in ferrets to a commercially available TIV with the responses to the same vaccine mixed with the CAF01 adjuvant. Two recently circulating H1N1 viruses were used as challenge to test the vaccine efficacy. CAF01 improved the immunogenicity of the vaccine, with increased influenza-specific IgA and IgG levels. Additionally, CAF01 promoted cellular-mediated immunity as indicated by interferon-gamma expressing lymphocytes, measured by flow cytometry. CAF01 also enhanced the protection conferred by the vaccine by reducing the viral load measured in nasal washes by RT-PCR. Finally, CAF01 allowed for dose-reduction and led to higher levels of protection compared to TIV adjuvanted with a squalene emulsion. The data obtained in this human-relevant challenge model supports the potential of CAF01 in future influenza vaccines.

  16. Intranasal Administration of Whole Inactivated Influenza Virus Vaccine as a Promising Influenza Vaccine Candidate.

    Science.gov (United States)

    Ainai, Akira; Suzuki, Tadaki; Tamura, Shin-Ichi; Hasegawa, Hideki

    The effect of the current influenza vaccine, an inactivated virus vaccine administered by subcutaneous/intramuscular injection, is limited to reducing the morbidity and mortality associated with seasonal influenza outbreaks. Intranasal vaccination, by contrast, mimics natural infection and induces not only systemic IgG antibodies but also local secretory IgA (S-IgA) antibodies found on the surface of the mucosal epithelium in the upper respiratory tract. S-IgA antibodies are highly effective at preventing virus infection. Although the live attenuated influenza vaccine (LAIV) administered intranasally can induce local antibodies, this vaccine is restricted to healthy populations aged 2-49 years because of safety concerns associated with using live viruses in a vaccine. Instead of LAIV, an intranasal vaccine made with inactivated virus could be applied to high-risk populations, including infants and elderly adults. Normally, a mucosal adjuvant would be required to enhance the effect of intranasal vaccination with an inactivated influenza vaccine. However, we found that intranasal administration of a concentrated, whole inactivated influenza virus vaccine without any mucosal adjuvant was enough to induce local neutralizing S-IgA antibodies in the nasal epithelium of healthy individuals with some immunological memory for seasonal influenza viruses. This intranasal vaccine is a novel candidate that could improve on the current injectable vaccine or the LAIV for the prevention of seasonal influenza epidemics.

  17. IgA polymerization contributes to efficient virus neutralization on human upper respiratory mucosa after intranasal inactivated influenza vaccine administration.

    Science.gov (United States)

    Terauchi, Yoshihiko; Sano, Kaori; Ainai, Akira; Saito, Shinji; Taga, Yuki; Ogawa-Goto, Kiyoko; Tamura, Shin-Ichi; Odagiri, Takato; Tashiro, Masato; Fujieda, Mikiya; Suzuki, Tadaki; Hasegawa, Hideki

    2018-02-09

    Unlike the current injectable influenza vaccines, intranasally administered influenza vaccines induce influenza virus-specific IgA antibodies in the local respiratory mucosa as well as IgG antibodies in the systemic circulation. Our previous study showed that after five volunteers underwent intranasal administration with inactivated H3N2 or H5N1 vaccines, their IgA antibodies on the upper respiratory tract were present as monomers, dimers, and multimers (trimers and tetramers). Moreover, the multimers associated with the highest virus neutralizing activity. However, it has remained elusive whether a more practical intranasal vaccination strategy could induce the high-performance IgA multimers in the nasal mucosa. In the present study, volunteers were administered with two doses of the intranasal trivalent whole-virus inactivated influenza vaccine and showed that in nasal wash samples the amount of multimeric IgA correlated positively with virus neutralizing titers, indicating that the multimeric IgA antibodies play an important role in the antiviral activity at the nasal mucosa. Surface plasmon resonance analysis of the binding dynamics of nasal wash derived IgA monomers, dimers, and multimers against recombinant trimeric influenza virus HA showed that sample fractions containing IgA multimers dissociated from HA less well than sample fractions without IgA multimers. Thus, IgA multimers may "stick" to the antigen more tightly than the other structures. In summary, intranasal administration of two doses of multivalent inactivated influenza vaccines induced multimeric IgA. Multimerization of mucosal IgA antibodies conferred higher neutralizing activity against viruses in the nasal mucosa, possibly by increasing their cohesion to virus antigens. (243 words Limit: 250 words).

  18. Potential impact of B lineage mismatch on trivalent influenza vaccine effectiveness during the 2015-2016 influenza season among nursery school children in Suzhou, China.

    Science.gov (United States)

    Wang, Yin; Chen, Liling; Cheng, Yuejia; Zhou, Suizan; Pang, Yuanyuan; Zhang, Jun; Greene, Carolyn M; Song, Ying; Zhang, Tao; Zhao, Genming

    2018-03-04

    We actively followed a cohort of nursery school children in Suzhou, China to assess the impact of vaccination with trivalent influenza vaccine on the prevention of influenza like illness (ILI). We enrolled children aged 36 to 72 months from 13 nursery schools in Suzhou starting two weeks after vaccination during October 2015-February 2016. Every school-day, teachers reported the names of students with ILI to study clinicians, who collected the student's nasopharyngeal swab or throat swab, either at a study clinic or the child's home. Swabs were sent to the Suzhou Center for Disease Control and Prevention's laboratory for influenza testing by RT-PCR. In total, 3278 children were enrolled; 83 (3%) were lost to follow-up, while 3195 (vaccinated: 1492, unvaccinated: 1703) were followed for 24 weeks. During the study, 40 samples tested positive; 17 in the vaccinated (B Victoria: 12; A(H1N1)pdm09: 5) and 23 in the unvaccinated group (B Victoria: 10; B Yamagata: 2; A(H1N1)pdm09: 11). The VE estimates were: 16% overall (95%CI:-58%,56%), 48% (-47%,84%) for influenza A(H1N1)pdm09, 43% (-650%,98%) for influenza B Yamagata, and -37% (-227%,42%) for influenza B Victoria. Data were analyzed by vaccinated and unvaccinated groups based on enrollees' vaccination records. The VE for A(H1N1)pdm09 was moderate but not significant. Mismatching of B lineage may have compromised trivalent influenza vaccine effectiveness during the 2015-2016 influenza season among nursery school children in Suzhou, China. Additional larger studies are warranted to inform policy related to quadrivalent influenza vaccine licensure in China in the future.

  19. Phase III, randomized controlled trial to evaluate lot consistency of a trivalent subunit egg-based influenza vaccine in adults.

    Science.gov (United States)

    Rivera, Luis; Mazara, Sonia; Vargas, Maria; Fragapane, Elena; Casula, Daniela; Groth, Nicola

    2012-07-27

    Vaccination is the most effective preventive strategy to control influenza. The demonstration of lot-to-lot consistency to confirm the reliability of the manufacturing process has become a mandatory step in vaccine development. This phase III, observer-blind, controlled trial assessed lot-to-lot consistency, immunogenicity, and safety of a subunit trivalent influenza vaccine (Agrippal®, Novartis Vaccines and Diagnostics) in healthy adults aged 18-49 years. The immunogenicity and safety profile of Agrippal was compared with a control vaccine (Fluvirin®, Novartis Vaccines and Diagnostics). A total of 1507 subjects were randomized 2:2:2:1 to receive one vaccination of one of the three lots of influenza vaccine or control vaccine. Antibody levels were measured by hemagglutination inhibition assay on days 1 and 22. Adverse reactions were solicited via diary cards for 7 days after vaccination, and unsolicited adverse events were collected throughout the study period. Equivalence of day 22 immune responses to the three lots was shown for each of the three strains. Robust immunogenic responses after one dose were observed for all vaccine groups, and both Center for Biologics Evaluation and Research criteria for licensure of influenza vaccines were met for all three virus strains. Both vaccines exhibited a robust safety profile and were well tolerated, with no differences in local and systemic solicited reactions or in unsolicited adverse events. The demonstration of consistency between manufacturing lots confirms for purposes of clinical development the reliability of the production process. The robust immunogenic responses and favorable safety profiles further support the use of trivalent subunit influenza vaccines Agrippal and Fluvirin for active immunization against influenza. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. Concurrent and cross-season protection of inactivated influenza vaccine against A(H1N1)pdm09 illness among young children: 2012-2013 case-control evaluation of influenza vaccine effectiveness.

    Science.gov (United States)

    Fu, Chuanxi; Xu, Jianxiong; Lin, Jinyan; Wang, Ming; Li, Kuibiao; Ge, Jing; Thompson, Mark G

    2015-06-09

    In 2012-2013, we examined 1729 laboratory-confirmed A(H1N1)pdm09 influenza cases matched 1:1 with healthy controls and estimated influenza vaccine effectiveness (VE) for trivalent inactivated influenza vaccine (IIV3) to be 67% (95% confidence interval=58-74%) for ages 8 months to 6 years old. Among children aged 8-35 months old, VE for fully vaccinated children (73%, 60-81%) was significantly higher than VE for partially vaccinated children (55%, 33-70%). Significant cross-season protection from prior IIV3 was noted, including VE of 31% (8-48%) from IIV3 received in 2010-2011 against influenza illness in 2012--2013 without subsequent boosting doses. Published by Elsevier Ltd.

  1. Standardisation of inactivated influenza vaccines-Learning from history.

    Science.gov (United States)

    Wood, John M; Weir, Jerry P

    2018-03-01

    The single radial immunodiffusion assay has been the accepted method for determining the potency of inactivated influenza vaccines since 1978. The worldwide adoption of this assay for vaccine standardisation was facilitated through collaborative studies that demonstrated a high level of reproducibility and its applicability to the different types of influenza vaccine being produced at that time. Clinical evidence indicated the relevance of SRID as a potency assay. Unique features of the SRID assay are likely responsible for its longevity even as newer technologies for vaccine characterisation have been developed and refined. Nevertheless, there are significant limitations to the SRID assay that indicate the need for improvement, and there has been a substantial amount of work undertaken in recent years to develop and evaluate alternative potency assays, including collaborative studies involving research laboratories, regulatory agencies and vaccine manufacturers. Here, we provide an overview of the history of inactivated influenza vaccine potency testing, the current state of alternative assay development and the some of the major challenges to be overcome before implementation of new assays for potency determination. © 2018 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

  2. Intranasal Inactivated Influenza Vaccines: a Reasonable Approach to Improve the Efficacy of Influenza Vaccine?

    Science.gov (United States)

    Tamura, Shin-Ichi; Ainai, Akira; Suzuki, Tadaki; Kurata, Takeshi; Hasegawa, Hideki

    2016-01-01

    Influenza is a contagious, acute respiratory disease caused by the influenza virus. The mucosal lining in the host respiratory tract is not only the site of virus infection, but also the site of defense; it is at this site that the host immune response targets the virus and protects against reinfection. One of the most effective methods to prevent influenza is to induce specific antibody (Ab) responses in the respiratory tract by vaccination. Two types of influenza vaccines, intranasal live attenuated influenza virus (LAIV) vaccines and parenteral (injectable) inactivated vaccines, are currently used worldwide. These vaccines are approved by the European Medicines Agency (EMA) and the US Food and Drug Administration. Live attenuated vaccines induce both secretory IgA (S-IgA) and serum IgG antibodies (Abs), whereas parenteral vaccines induce only serum IgG Abs. However, intranasal administration of inactivated vaccines together with an appropriate adjuvant induces both S-IgA and IgG Abs. Several preclinical studies on adjuvant-combined, nasal-inactivated vaccines revealed that nasal S-IgA Abs, a major immune component in the upper respiratory tract, reacted with homologous virus hemagglutinin (HA) and were highly cross-reactive with viral HA variants, resulting in protection and cross-protection against infection by both homologous and variant viruses, respectively. Serum-derived IgG Abs, which are present mainly in the lower respiratory tract, are less cross-reactive and cross-protective. In addition, our own clinical trials have shown that nasal-inactivated whole virus vaccines, including a built-in adjuvant (single-stranded RNA), induced serum hemagglutination inhibition (HI) Ab titers that fulfilled the EMA criteria for vaccine efficacy. The nasal-inactivated whole virus vaccines also induced high levels of nasal HI and neutralizing Ab titers, although we have not yet evaluated the nasal HI titers due to the lack of official criteria to establish efficacy based

  3. Vaccine failure and serologic response to live attenuated and inactivated influenza vaccines in children during the 2013-2014 season.

    Science.gov (United States)

    King, Jennifer P; McLean, Huong Q; Meece, Jennifer K; Levine, Min Z; Spencer, Sarah M; Flannery, Brendan; Belongia, Edward A

    2018-02-21

    Recent observational studies in the United States indicated live attenuated influenza vaccine (LAIV) was less effective in children against clinical influenza infection caused by A(H1N1)pdm09 relative to inactivated influenza vaccine (IIV). During the 2013-2014 influenza season, we conducted an observational study among children aged 5-17 years to compare serologic responses to LAIV and IIV and explore factors associated with vaccine failure. One hundred and sixty-one children received one dose of trivalent IIV or quadrivalent LAIV according to parental preference. Baseline and postvaccination serum samples were tested with hemagglutination inhibition (HI) assays against vaccine reference strains. Geometric mean titers (GMT), geometric mean fold rise (GMFR), seroconversion, and seroprotection (HI titer ≥ 40) were used to assess response to vaccine. Active surveillance for acute respiratory illness was conducted during the influenza season and influenza cases were confirmed by reverse transcription polymerase chain reaction (RT-PCR). Logistic regression was used to examine the association between vaccine type and vaccine failure. LAIV and IIV recipients were similar with respect to demographics and baseline GMT for each vaccine strain. RT-PCR confirmed influenza (vaccine failure) occurred in 8 (13%) of 62 LAIV recipients and 3 (3%) of 99 IIV recipients (p = .02). Postvaccination GMFR for A(H1N1)pdm09 was higher for IIV vs LAIV receipt (GMFR 3.3 vs. 0.8, p vaccine failure in the age-adjusted multivariable model (odds ratio 4.5, 95% CI 1.1-18.2). Receipt of LAIV generated minimal HI antibody response in children, including among those seronegative at baseline. LAIV recipients had significant increased risk of A(H1N1)pdm09 infection compared to IIV recipients. Copyright © 2018 Elsevier Ltd. All rights reserved.

  4. Human Phase 1 trial of low-dose inactivated seasonal influenza vaccine formulated with Advax™ delta inulin adjuvant.

    Science.gov (United States)

    Gordon, David L; Sajkov, Dimitar; Honda-Okubo, Yoshikazu; Wilks, Samuel H; Aban, Malet; Barr, Ian G; Petrovsky, Nikolai

    2016-07-19

    Influenza vaccines are usually non-adjuvanted but addition of adjuvant may improve immunogenicity and permit dose-sparing, critical for vaccine supply in the event of an influenza pandemic. The aim of this first-in-man study was to determine the effect of delta inulin adjuvant on the safety and immunogenicity of a reduced dose seasonal influenza vaccine. Healthy male and female adults aged 18-65years were recruited to participate in a randomized controlled study to compare the safety, tolerability and immunogenicity of a reduced-dose 2007 Southern Hemisphere trivalent inactivated influenza vaccine formulated with Advax™ delta inulin adjuvant (LTIV+Adj) when compared to a full-dose of the standard TIV vaccine which does not contain an adjuvant. LTIV+Adj provided equivalent immunogenicity to standard TIV vaccine as assessed by hemagglutination inhibition (HI) assays against each vaccine strain as well as against a number of heterosubtypic strains. HI responses were sustained at 3months post-immunisation in both groups. Antibody landscapes against a large panel of H3N2 influenza viruses showed distinct age effects whereby subjects over 40years old had a bimodal baseline HI distribution pattern, with the highest HI titers against the very oldest H3N2 isolates and with a second HI peak against influenza isolates from the last 5-10years. By contrast, subjects >40years had a unimodal baseline HI distribution with peak recognition of H3N2 isolates from approximately 20years ago. The reduced dose TIV vaccine containing Advax adjuvant was well tolerated and no safety issues were identified. Hence, delta inulin may be a useful adjuvant for use in seasonal or pandemic influenza vaccines. Australia New Zealand Clinical Trial Registry: ACTRN12607000599471. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Immunogenicity and safety of a quadrivalent inactivated influenza virus vaccine compared with a comparator quadrivalent inactivated influenza vaccine in a pediatric population: A phase 3, randomized noninferiority study.

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    Airey, Jolanta; Albano, Frank R; Sawlwin, Daphne C; Jones, Alison Graves; Formica, Neil; Matassa, Vince; Leong, Jane

    2017-05-09

    Seqirus 2010 Southern Hemisphere split-virion trivalent inactivated influenza vaccine (IIV3) was associated with increased febrile reactions in children. Studies in vitro concluded that increasing concentrations of splitting agent decreased residual lipids and attenuated proinflammatory cytokine signals associated with fever. We assessed immunogenicity and safety of a quadrivalent inactivated influenza vaccine (IIV4; produced using higher concentration of splitting agent) versus a United States-licensed comparator IIV4 in healthy children aged 5-17years. Participants (N=2278) were randomized 3:1 and stratified by age (5-8years; 9-17years) to receive IIV4 (n=1709) or comparator IIV4 (n=569). Primary objective was to demonstrate noninferiority of IIV4 versus comparator IIV4 as assessed by hemagglutination inhibition (HI) geometric mean titer (GMT) ratio (upper bound of two-sided 95% confidence interval [CI]≤1.5) and difference in seroconversion rate (upper bound of two-sided 95% CI≤10%) for all four vaccine strains. HI antibody titers were assessed at baseline and 28days postvaccination. Solicited and unsolicited adverse events were assessed during each 7- and 28-day postvaccination period, respectively. IIV4 met immunogenicity criteria for noninferiority. Adjusted GMT ratios (comparator IIV4/IIV4) for A/H1N1, A/H3N2, B/Yamagata, and B/Victoria strains were 1.01 (95% CI; 0.93, 1.09), 1.05 (0.96, 1.15), 0.89 (0.81, 0.98), and 0.92 (0.83, 1.02), respectively. Corresponding values for differences (95% CI) in seroconversion rates (comparator IIV4 minus IIV4) were -3.1 (-8.0, 1.8), 0.4 (-4.5, 5.3), -3.4 (-8.3, 1.5), and -2.0 (-6.9, 2.9). Fever rates were numerically higher, but not statistically different, with IIV4 versus comparator IIV4. No new safety signals were reported. IIV4 demonstrated immunological noninferiority to the comparator IIV4 with a clinically acceptable safety profile in children aged 5-17years. Increased levels of virus splitting agent seem to

  6. Phase IV: randomized controlled trial to evaluate lot consistency of trivalent split influenza vaccines in healthy adults.

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    Song, Joon Young; Cheong, Hee Jin; Lee, Jacob; Wie, Seong-Heon; Park, Kyung-Hwa; Kee, Sae Yoon; Jeong, Hye Won; Kim, Yeon-Sook; Noh, Ji Yun; Choi, Won Suk; Park, Dae Won; Sohn, Jang Wook; Kim, Woo Joo

    2014-01-01

    Influenza vaccines are the primary method for preventing influenza and its complications. Considering the increasing demand for influenza vaccines, vaccine manufacturers are required to establish large-scale production systems. This phase IV randomized trial was conducted to evaluate the lot consistency of trivalent split influenza vaccines regarding immunogenicity and safety. A total of 1,023 healthy adults aged 18-64 y were enrolled in the study. Subjects were randomly assigned in a 1:1 ratio to receive the GC FLU® Prefilled Syringe or the GC FLU® Injection, and they were further randomized to one of 3 lots of each vaccine in a 1:1:1 ratio. In both GC FLU® Injection and GC FLU® Prefilled Syringe groups, immune responses were equivalent between lots for each of the 3 vaccine strains on day 21. The 2-sided 95% CI of GMT ratios between pairs of lots were between 0.67 and 1.5, meeting the equivalence criteria. After vaccination, all 3 criteria of the European Medicines Agency were met in both GC FLU® Injection and GC FLU® Prefilled Syringe groups. The vaccines showed tolerable safety profiles without serious adverse events. The demonstration of lot consistency, robust immunogenic responses and favorable safety profiles support the reliability of mass-manufacturing systems for the GC FLU® Injection and GC FLU® Prefilled Syringe.

  7. Safety, efficacy, and immunogenicity of an inactivated influenza vaccine in healthy adults: a randomized, placebo-controlled trial over two influenza seasons

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    Bouveret Nancy

    2010-03-01

    Full Text Available Abstract Background Seasonal influenza imposes a substantial personal morbidity and societal cost burden. Vaccination is the major strategy for influenza prevention; however, because antigenically drifted influenza A and B viruses circulate annually, influenza vaccines must be updated to provide protection against the predicted prevalent strains for the next influenza season. The aim of this study was to assess the efficacy, safety, reactogenicity, and immunogenicity of a trivalent inactivated split virion influenza vaccine (TIV in healthy adults over two influenza seasons in the US. Methods The primary endpoint of this double-blind, randomized study was the average efficacy of TIV versus placebo for the prevention of vaccine-matched, culture-confirmed influenza (VMCCI across the 2005-2006 and 2006-2007 influenza seasons. Secondary endpoints included the prevention of laboratory-confirmed (defined by culture and/or serology influenza, as well as safety, reactogenicity, immunogenicity, and consistency between three consecutive vaccine lots. Participants were assessed actively during both influenza seasons, and nasopharyngeal swabs were collected for viral culture from individuals with influenza-like illness. Blood specimens were obtained for serology one month after vaccination and at the end of each influenza season's surveillance period. Results Although the point estimate for efficacy in the prevention of all laboratory-confirmed influenza was 63.2% (97.5% confidence interval [CI] lower bound of 48.2%, the point estimate for the primary endpoint, efficacy of TIV against VMCCI across both influenza seasons, was 46.3% with a 97.5% CI lower bound of 9.8%. This did not satisfy the pre-specified success criterion of a one-sided 97.5% CI lower bound of >35% for vaccine efficacy. The VMCCI attack rates were very low overall at 0.6% and 1.2% in the TIV and placebo groups, respectively. Apart from a mismatch for influenza B virus lineage in 2005

  8. THE ANTIGENIC POTENCY OF EPIDEMIC INFLUENZA VIRUS FOLLOWING INACTIVATION BY ULTRAVIOLET RADIATION

    Science.gov (United States)

    Salk, Jonas E.; Lavin, G. I.; Francis, Thomas

    1940-01-01

    A study of the antigenic potency of influenza virus inactivated by ultraviolet radiation has been made. Virus so inactivated is still capable of functioning as an immunizing agent when given to mice by the intraperitoneal route. In high concentrations inactivated virus appears to be nearly as effective as active virus but when quantitative comparisons of the immunity induced by different dilutions are made, it is seen that a hundredfold loss in immunizing capacity occurs during inactivation. Virus in suspensions prepared from the lungs of infected mice is inactivated more rapidly than virus in tissue culture medium. A standard for the comparison of vaccines of epidemic influenza virus is proposed. PMID:19871057

  9. Intranasal Immunization Using Mannatide as a Novel Adjuvant for an Inactivated Influenza Vaccine and Its Adjuvant Effect Compared with MF59.

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    Shu-Ting Ren

    Full Text Available Intranasal vaccination is more potent than parenteral injection for the prevention of influenza. However, because the poor efficiency of antigen uptake across the nasal mucosa is a key issue, immunostimulatory adjuvants are essential for intranasal vaccines. The immunomodulator mannatide or polyactin (PA has been used for the clinical treatment of impaired immunity in China, but its adjuvant effect on an inactivated trivalent influenza vaccine (ITIV via intranasal vaccination is unclear. To explore the adjuvant effect of PA, an inactivated trivalent influenza virus with or without PA or MF59 was instilled intranasally once a week in BALB/c mice. Humoral immunity was assessed by both the ELISA and hemagglutination inhibition (HI methods using antigen-specific antibodies. Splenic lymphocyte proliferation and the IFN-γ level were measured to evaluate cell-mediated immunity. The post-vaccination serum HI antibody geometric mean titers (GMTs for the H1N1 and H3N2 strains, antigen-specific serum IgG and IgA GMTs, mucosal SIgA GMT, splenic lymphocyte proliferation, and IFN-γ were significantly increased in the high-dose PA-adjuvanted vaccine group. The seroconversion rate and the mucosal response for the H3N2 strain were significantly elevated after high-dose PA administration. These adjuvant effects of high-dose PA for the influenza vaccine were comparable with those of the MF59 adjuvant, and abnormal signs or pathological changes were not found in the evaluated organs. In conclusion, PA is a novel mucosal adjuvant for intranasal vaccination with the ITIV that has safe and effective mucosal adjuvanticity in mice and successfully induces both serum and mucosal antibody responses and a cell-mediated response.

  10. Influenza (flu) vaccine (Inactivated or Recombinant): What you need to know

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    Vaccine Information Statement. Influenza (Flu) Vaccine (Inactivated or Recombinant): What you need to know. Centers for Disease Control and Prevention website at www.cdc.gov/vaccines/hcp/vis/vis-statements/ ...

  11. Dietary Enterococcus faecium NCIMB 10415 and zinc oxide stimulate immune reactions to trivalent influenza vaccination in pigs but do not affect virological response upon challenge infection.

    Science.gov (United States)

    Wang, Zhenya; Burwinkel, Michael; Chai, Weidong; Lange, Elke; Blohm, Ulrike; Breithaupt, Angele; Hoffmann, Bernd; Twardziok, Sven; Rieger, Juliane; Janczyk, Pawel; Pieper, Robert; Osterrieder, Nikolaus

    2014-01-01

    Swine influenza viruses (SIV) regularly cause significant disease in pigs worldwide. Since there is no causative treatment of SIV, we tested if probiotic Enterococcus (E.) faecium NCIMB 10415 or zinc (Zn) oxide as feed supplements provide beneficial effects upon SIV infection in piglets. Seventy-two weaned piglets were fed three different diets containing either E. faecium or different levels of Zn (2500 ppm, Zn(high); 50 ppm, Zn(low)). Half of the piglets were vaccinated intramuscularly (VAC) twice with an inactivated trivalent SIV vaccine, while all piglets were then infected intranasally with H3N2 SIV. Significantly higher weekly weight gains were observed in the E. faecium group before virus infection, and piglets in Zn(high) and E. faecium groups gained weight after infection while those in the control group (Zn(low)) lost weight. Using ELISA, we found significantly higher H3N2-specific antibody levels in the E. faecium+VAC group 2 days before and at the day of challenge infection as well as at 4 and 6 days after challenge infection. Higher hemagglutination inhibition (HI) titers were also observed in the Zn(high)+VAC and E. faecium+VAC groups at 0, 1 and 4 days after infection. However, there were no significant differences in virus shedding and lung lesions between the dietary groups. Using flow cytometry analysis significantly higher activated T helper cells and cytotoxic T lymphocyte percentages in the PBMCs were detected in the Zn(high) and E. faecium groups at single time points after infection compared to the Zn(low) control group, but no prolonged effect was found. In the BAL cells no influence of dietary supplementation on immune cell percentages could be detected. Our results suggest that feeding high doses of zinc oxide and particularly E. faecium could beneficially influence humoral immune responses after vaccination and recovery from SIV infection, but not affect virus shedding and lung pathology.

  12. Dietary Enterococcus faecium NCIMB 10415 and zinc oxide stimulate immune reactions to trivalent influenza vaccination in pigs but do not affect virological response upon challenge infection.

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    Zhenya Wang

    Full Text Available Swine influenza viruses (SIV regularly cause significant disease in pigs worldwide. Since there is no causative treatment of SIV, we tested if probiotic Enterococcus (E. faecium NCIMB 10415 or zinc (Zn oxide as feed supplements provide beneficial effects upon SIV infection in piglets. Seventy-two weaned piglets were fed three different diets containing either E. faecium or different levels of Zn (2500 ppm, Zn(high; 50 ppm, Zn(low. Half of the piglets were vaccinated intramuscularly (VAC twice with an inactivated trivalent SIV vaccine, while all piglets were then infected intranasally with H3N2 SIV. Significantly higher weekly weight gains were observed in the E. faecium group before virus infection, and piglets in Zn(high and E. faecium groups gained weight after infection while those in the control group (Zn(low lost weight. Using ELISA, we found significantly higher H3N2-specific antibody levels in the E. faecium+VAC group 2 days before and at the day of challenge infection as well as at 4 and 6 days after challenge infection. Higher hemagglutination inhibition (HI titers were also observed in the Zn(high+VAC and E. faecium+VAC groups at 0, 1 and 4 days after infection. However, there were no significant differences in virus shedding and lung lesions between the dietary groups. Using flow cytometry analysis significantly higher activated T helper cells and cytotoxic T lymphocyte percentages in the PBMCs were detected in the Zn(high and E. faecium groups at single time points after infection compared to the Zn(low control group, but no prolonged effect was found. In the BAL cells no influence of dietary supplementation on immune cell percentages could be detected. Our results suggest that feeding high doses of zinc oxide and particularly E. faecium could beneficially influence humoral immune responses after vaccination and recovery from SIV infection, but not affect virus shedding and lung pathology.

  13. Inactivation of various influenza strains to model avian influenza (Bird Flu) with various disinfectant chemistries.

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    Oberst, R. D.; Bieker, Jill Marie; Souza, Caroline Ann

    2005-12-01

    Due to the grave public health implications and economic impact possible with the emergence of the highly pathogenic avian influenza A isolate, H5N1, currently circulating in Asia we have evaluated the efficacy of various disinfectant chemistries against surrogate influenza A strains. Chemistries included in the tests were household bleach, ethanol, Virkon S{reg_sign}, and a modified version of the Sandia National Laboratories developed DF-200 (DF-200d, a diluted version of the standard DF-200 formulation). Validation efforts followed EPA guidelines for evaluating chemical disinfectants against viruses. The efficacy of the various chemistries was determined by infectivity, quantitative RNA, and qualitative protein assays. Additionally, organic challenges using combined poultry feces and litter material were included in the experiments to simulate environments in which decontamination and remediation will likely occur. In all assays, 10% bleach and Sandia DF-200d were the most efficacious treatments against two influenza A isolates (mammalian and avian) as they provided the most rapid and complete inactivation of influenza A viruses.

  14. Immunopotentiation of trivalent influenza vaccine when given with VAX102, a recombinant influenza M2e vaccine fused to the TLR5 ligand flagellin.

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    H Keipp Talbot

    Full Text Available BACKGROUND: Currently controversy exists about the immunogenicity of seasonal trivalent influenza vaccine in certain populations, especially the elderly. STF2.4×M2e (VAX102 is a recombinant fusion protein that links four copies of the ectodomain of influenza virus matrix protein 2 (M2e antigen to Salmonella typhimurium flagellin, a TLR5 ligand. The objectives of this study were to assess the feasibility of giving VAX102 and TIV in combination in an effort to achieve greater immunogenicity and to provide cross-protection. METHODOLOGY/PRINCIPAL FINDINGS: Eighty healthy subjects, 18-49 years old, were enrolled in May and June 2009 in a double-blind, randomized, controlled trial at two clinical sites. Subjects were randomized to receive either TIV + VAX102 or TIV + placebo. Both arms tolerated the vaccines. Pain at the injection site was more severe with TIV + VAX102. Two weeks after immunization the HAI responses to the H1 and H3 antigens of TIV were higher in those that received TIV + VAX102 than in TIV + placebo (309 vs 200 and 269 vs 185, respectively, although statistically non-significant. There was no difference in the HAI of the B antigen. In the TIV + VAX102 arm, the geometric mean M2e antibody concentration was 0.5 µg/ml and 73% seroconverted. CONCLUSIONS/SIGNIFICANCE: The combination of TIV + VAX102 has the potential to increase the immune response to the influenza A components of TIV and to provide M2e immunity which may protect against influenza A strains not contained in seasonal TIV. TRIAL REGISTRATION: ClinicalTrials.gov NCT00921973.

  15. Cost Effectiveness of Influenza Vaccine for U.S. Children: Live Attenuated and Inactivated Influenza Vaccine.

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    Shim, Eunha; Brown, Shawn T; DePasse, Jay; Nowalk, Mary Patricia; Raviotta, Jonathan M; Smith, Kenneth J; Zimmerman, Richard K

    2016-09-01

    Prior studies showed that live attenuated influenza vaccine (LAIV) is more effective than inactivated influenza vaccine (IIV) in children aged 2-8 years, supporting the Centers for Disease Control and Prevention (CDC) recommendations in 2014 for preferential LAIV use in this age group. However, 2014-2015 U.S. effectiveness data indicated relatively poor effectiveness of both vaccines, leading CDC in 2015 to no longer prefer LAIV. An age-structured model of influenza transmission and vaccination was developed, which incorporated both direct and indirect protection induced by vaccination. Based on this model, the cost effectiveness of influenza vaccination strategies in children aged 2-8 years in the U.S. was estimated. The base case assumed a mixed vaccination strategy where 33.3% and 66.7% of vaccinated children aged 2-8 years receive LAIV and IIV, respectively. Analyses were performed in 2014-2015. Using published meta-analysis vaccine effectiveness data (83% LAIV and 64% IIV), exclusive LAIV use would be a cost-effective strategy when vaccinating children aged 2-8 years, whereas IIV would not be preferred. However, when 2014-2015 U.S. effectiveness data (0% LAIV and 15% IIV) were used, IIV was likely to be preferred. The cost effectiveness of influenza vaccination in children aged 2-8 years is highly dependent on vaccine effectiveness; the vaccine type with higher effectiveness is preferred. In general, exclusive IIV use is preferred over LAIV use, as long as vaccine effectiveness is higher for IIV than for LAIV. Copyright © 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

  16. Influenza immunization during pregnancy: Benefits for mother and infant

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    Sakala, Isaac G.; Honda-Okubo, Yoshikazu; Fung, Johnson; Petrovsky, Nikolai

    2016-01-01

    The serious consequences of influenza infection during pregnancy have been recognized for almost a century. In this article, we reviewed the evidence on the immunogenicity, safety and impact of maternal influenza immunization for both mother and child. After vaccination, pregnant women have similar protective titers of anti-influenza antibodies as non-pregnant women, demonstrating that pregnancy does not alter the trivalent inactivated influenza vaccine immune response. Studies from the Unite...

  17. Polymyositis following Pandemic Influenza A (H1N1 and 2009-10 Seasonal Trivalent Vaccines

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    Clodoveo Ferri

    2012-01-01

    Full Text Available Sporadic associations between inflammatory myopathies with vaccinations were described in the literature, raising the possible trigger value of vaccines in the development of these autoimmune disorders. Here, we reported the clinical history of 3 patients who developed polymyositis complicated by interstitial lung disease (2 cases and dermatomyositis (1 case, after influenza A (H1N1 vaccination.

  18. Low pH gel intranasal sprays inactivate influenza viruses in vitro and protect ferrets against influenza infection

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    Lambkin-Williams Robert

    2007-05-01

    Full Text Available Abstract Background Developing strategies for controlling the severity of pandemic influenza is a global public health priority. In the event of a pandemic there may be a place for inexpensive, readily available, effective adjunctive therapies to support containment strategies such as prescription antivirals, vaccines, quarantine and restrictions on travel. Inactivation of virus in the intranasal environment is one possible approach. The work described here investigated the sensitivity of influenza viruses to low pH, and the activity of low pH nasal sprays on the course of an influenza infection in the ferret model. Methods Inactivation of influenza A and avian reassortment influenza was determined using in vitro solutions tests. Low pH nasal sprays were tested using the ferret model with an influenza A Sydney/5/97 challenge. Clinical measures were shed virus, weight loss and body temperature. Results The virus inactivation studies showed that influenza viruses are rapidly inactivated by contact with acid buffered solutions at pH 3.5. The titre of influenza A Sydney/5/97 [H3N2] was reduced by at least 3 log cycles with one minute contact with buffers based on simple acid mixtures such as L-pyroglutamic acid, succinic acid, citric acid and ascorbic acid. A pH 3.5 nasal gel composition containing pyroglutamic acid, succinic acid and zinc acetate reduced titres of influenza A Hong Kong/8/68 [H3N2] by 6 log cycles, and avian reassortment influenza A/Washington/897/80 X A Mallard/New York/6750/78 [H3N2] by 5 log cycles, with 1 min contact. Two ferret challenge studies, with influenza A Sydney/5/97, demonstrated a reduction in the severity of the disease with early application of low pH nasal sprays versus a saline control. In the first study there was decreased weight loss in the treatment groups. In the second study there were reductions in virus shedding and weight loss, most notably when a gelling agent was added to the low pH formulation

  19. Inactivated Eyedrop Influenza Vaccine Adjuvanted with Poly(I:C Is Safe and Effective for Inducing Protective Systemic and Mucosal Immunity.

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    Eun-Do Kim

    Full Text Available The eye route has been evaluated as an efficient vaccine delivery routes. However, in order to induce sufficient antibody production with inactivated vaccine, testing of the safety and efficacy of the use of inactivated antigen plus adjuvant is needed. Here, we assessed various types of adjuvants in eyedrop as an anti-influenza serum and mucosal Ab production-enhancer in BALB/c mice. Among the adjuvants, poly (I:C showed as much enhancement in antigen-specific serum IgG and mucosal IgA antibody production as cholera toxin (CT after vaccinations with trivalent hemagglutinin-subunits or split H1N1 vaccine antigen in mice. Vaccination with split H1N1 eyedrop vaccine antigen plus poly(I:C showed a similar or slightly lower efficacy in inducing antibody production than intranasal vaccination; the eyedrop vaccine-induced immunity was enough to protect mice from lethal homologous influenza A/California/04/09 (H1N1 virus challenge. Additionally, ocular inoculation with poly(I:C plus vaccine antigen generated no signs of inflammation within 24 hours: no increases in the mRNA expression levels of inflammatory cytokines nor in the infiltration of mononuclear cells to administration sites. In contrast, CT administration induced increased expression of IL-6 cytokine mRNA and mononuclear cell infiltration in the conjunctiva within 24 hours of vaccination. Moreover, inoculated visualizing materials by eyedrop did not contaminate the surface of the olfactory bulb in mice; meanwhile, intranasally administered materials defiled the surface of the brain. On the basis of these findings, we propose that the use of eyedrop inactivated influenza vaccine plus poly(I:C is a safe and effective mucosal vaccine strategy for inducing protective anti-influenza immunity.

  20. Comparison of egg and high yielding MDCK cell-derived live attenuated influenza virus for commercial production of trivalent influenza vaccine: in vitro cell susceptibility and influenza virus replication kinetics in permissive and semi-permissive cells.

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    Hussain, Althaf I; Cordeiro, Melissa; Sevilla, Elizabeth; Liu, Jonathan

    2010-05-14

    Currently MedImmune manufactures cold-adapted (ca) live, attenuated influenza vaccine (LAIV) from specific-pathogen free (SPF) chicken eggs. Difficulties in production scale-up and potential exposure of chicken flocks to avian influenza viruses especially in the event of a pandemic influenza outbreak have prompted evaluation and development of alternative non-egg based influenza vaccine manufacturing technologies. As part of MedImmune's effort to develop the live attenuated influenza vaccine (LAIV) using cell culture production technologies we have investigated the use of high yielding, cloned MDCK cells as a substrate for vaccine production by assessing host range and virus replication of influenza virus produced from both SPF egg and MDCK cell production technologies. In addition to cloned MDCK cells the indicator cell lines used to evaluate the impact of producing LAIV in cells on host range and replication included two human cell lines: human lung carcinoma (A549) cells and human muco-epidermoid bronchiolar carcinoma (NCI H292) cells. The influenza viruses used to infect the indicators cell lines represented both the egg and cell culture manufacturing processes and included virus strains that composed the 2006-2007 influenza seasonal trivalent vaccine (A/New Caledonia/20/99 (H1N1), A/Wisconsin/67/05 (H3N2) and B/Malaysia/2506/04). Results from this study demonstrate remarkable similarity between influenza viruses representing the current commercial egg produced and developmental MDCK cell produced vaccine production platforms. MedImmune's high yielding cloned MDCK cells used for the cell culture based vaccine production were highly permissive to both egg and cell produced ca attenuated influenza viruses. Both the A549 and NCI H292 cells regardless of production system were less permissive to influenza A and B viruses than the MDCK cells. Irrespective of the indicator cell line used the replication properties were similar between egg and the cell produced

  1. Influenza Vaccine Manufacturing: Effect of Inactivation, Splitting and Site of Manufacturing. Comparison of Influenza Vaccine Production Processes.

    Science.gov (United States)

    Kon, Theone C; Onu, Adrian; Berbecila, Laurentiu; Lupulescu, Emilia; Ghiorgisor, Alina; Kersten, Gideon F; Cui, Yi-Qing; Amorij, Jean-Pierre; Van der Pol, Leo

    2016-01-01

    The aim of this study was to evaluate the impact of different inactivation and splitting procedures on influenza vaccine product composition, stability and recovery to support transfer of process technology. Four split and two whole inactivated virus (WIV) influenza vaccine bulks were produced and compared with respect to release criteria, stability of the bulk and haemagglutinin recovery. One clarified harvest of influenza H3N2 A/Uruguay virus prepared on 25.000 fertilized eggs was divided equally over six downstream processes. The main unit operation for purification was sucrose gradient zonal ultracentrifugation. The inactivation of the virus was performed with either formaldehyde in phosphate buffer or with beta-propiolactone in citrate buffer. For splitting of the viral products in presence of Tween®, either Triton™ X-100 or di-ethyl-ether was used. Removal of ether was established by centrifugation and evaporation, whereas removal of Triton-X100 was performed by hydrophobic interaction chromatography. All products were sterile filtered and subjected to a 5 months real time stability study. In all processes, major product losses were measured after sterile filtration; with larger losses for split virus than for WIV. The beta-propiolactone inactivation on average resulted in higher recoveries compared to processes using formaldehyde inactivation. Especially ether split formaldehyde product showed low recovery and least stability over a period of five months.

  2. Whole-Inactivated Influenza Virus Is a Potent Adjuvant for Influenza Peptides Containing CD8+ T Cell Epitopes

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    Peter C. Soema

    2018-03-01

    Full Text Available Influenza peptide antigens coding for conserved T cell epitopes have the capacity to induce cross-protective influenza-specific immunity. Short peptide antigens used as a vaccine, however, often show poor immunogenicity. In this study, we demonstrate that whole-inactivated influenza virus (WIV acts as an adjuvant for influenza peptide antigens, as shown by the induction of peptide-specific CD8+ T cells in HLA-A2.1 transgenic mice upon vaccination with the influenza-M1-derived GILGFVFTL peptide (GIL, formulated with WIV. By screening various concentrations of GIL and WIV, we found that both components contributed to the GIL-specific T cell response. Whereas co-localization of the peptide antigen and WIV adjuvant was found to be important, neither physical association between peptide and WIV nor fusogenic activity of WIV were relevant for the adjuvant effect of WIV. We furthermore show that WIV may adjuvate T cell responses to a variety of peptides, using pools of either conserved wild-type influenza peptides or chemically altered peptide ligands. This study shows the potential of WIV as an adjuvant for influenza peptides. The simple formulation process and the solid safety record of WIV make this an attractive adjuvant for T cell peptides, and may also be used for non-influenza antigens.

  3. Immunogenicity and cross-reactivity of 2009-2010 inactivated seasonal influenza vaccine in US adults and elderly.

    Science.gov (United States)

    Xie, Hang; Jing, Xianghong; Li, Xing; Lin, Zhengshi; Plant, Ewan; Zoueva, Olga; Yang, Hong; Ye, Zhiping

    2011-01-31

    The campaign of 2009-2010 Northern Hemisphere seasonal vaccination was concurrent with the 2009 H1N1 pandemic. Using a hemagglutination inhibition (HAI) assay, we evaluated the immunogenicity and cross-reactivity of 2009-2010 inactivated trivalent influenza vaccine (TIV) in US adult and elderly populations. Vaccination of TIV resulted in a robust boost on the antibody response of all subjects to seasonal A/Brisbane/59/2007 (H1N1) and A/Uruguay/716/2007 (H3N2) with over 70% of recipients reaching a seroprotective titer of 40. B/Brisbane/60/2008 was the least immunogenic among the three seasonal vaccine strains with pandemic specific antibody responses. Twenty-four percent of adults and 36% of elderly reached a seroprotective HAI titer of 40 or more against pandemic A/South Carolina/18/2009 (H1N1) after receiving TIV compared to 4% and 7% at the beginning of vaccination, respectively. In addition, 22% of adults and 34% of elderly showed an increase of 4-fold or more in A/South Carolina/18/2009 specific HAI titers after TIV vaccination. The pandemic specific cross-reactive antibodies strongly correlated with the post-vaccination HAI titers against the seasonal H3N2 vaccine strain in all subjects.

  4. Influenza Vaccination in the Face of Immune Exhaustion: Is Herd Immunity Effective for Protecting the Elderly?

    OpenAIRE

    Lang, Pierre Olivier; Samaras, Dimitrios; Samaras, Nikolaos; Govind, Sheila; Aspinall, Richard

    2012-01-01

    At the start of the 21st century, seasonal influenza virus infection is still a major public health concern across the world. The recent body of evidence confirms that trivalent inactivated influenza vaccines (TIVs) are not optimal within the population who account for approximately 90% of all influenza-related death: elderly and chronically ill individuals regardless of age. With the ever increasing aging of the world population and the recent fears of any pandemic influenza rife, great effo...

  5. Effectiveness of live attenuated influenza vaccine and inactivated influenza vaccine in children during the 2014-2015 season.

    Science.gov (United States)

    McLean, Huong Q; Caspard, Herve; Griffin, Marie R; Poehling, Katherine A; Gaglani, Manjusha; Belongia, Edward A; Talbot, H Keipp; Peters, Timothy R; Murthy, Kempapura; Ambrose, Christopher S

    2017-05-09

    A clinical study found that live attenuated influenza vaccine (LAIV) was superior to inactivated influenza vaccine (IIV) against drifted A(H3N2) viruses in children. During the 2014-2015 influenza season, widespread circulation of antigenically and genetically drifted A(H3N2) viruses provided an opportunity to evaluate subtype-specific vaccine effectiveness (VE) of quadrivalent LAIV (LAIV4) and IIV in children. Children (2-17years) with febrile acute respiratory illness vaccination dates were obtained from medical records or immunization registries. VE was estimated using a test-negative design comparing odds of vaccination among influenza cases and test-negative controls with adjustment for potential confounders. Among 1696 children enrolled, 1511 (89%) were included in the analysis. Influenza was detected in 427 (28%) children; 317 had influenza A(H3N2) and 110 had influenza B. Most influenza isolates were characterized as a drifted strain of influenza A(H3N2) or a drifted strain of B/Yamagata. For LAIV4, adjusted VE was 50% (95% confidence interval [CI], 27-66%) against any influenza, 30% (95% CI, -6% to 54%) against influenza A(H3N2), and 87% (95% CI, 63-96%) against type B. For IIV, adjusted VE was 39% (95% CI, 18-54%) against any influenza, 40% (95% CI, 16-58%) against A(H3N2), and 29% (95% CI, -15% to 56%) against type B. Odds of influenza for LAIV4 versus IIV recipients were similar against influenza A(H3N2) (odds ratio [OR], 1.17; 95% CI, 0.73-1.86) and lower against influenza B (OR, 0.18; 95% CI, 0.06-0.55). LAIV4 and IIV provided similar protection against a new antigenic variant A(H3N2). LAIV4 provided significantly greater protection than IIV against a drifted influenza B strain. ClinicalTrials.gov identifier: NCT01997450. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  6. Development of a dried influenza whole inactivated virus vaccine for pulmonary immunization

    NARCIS (Netherlands)

    Audouy, Sandrine A.L.; van der Schaaf, Gieta; Hinrichs, Wouter L.J.; Frijlink, Henderik W.; Wilschut, Jan; Huckriede, Anke

    2011-01-01

    Stabilization and ease of administration are two ways to substantially improve the use of current vaccines. In the present study an influenza whole inactivated virus (WIV) vaccine was freeze-dried or spray-freeze dried in the presence of inulin as a cryoprotectant. Only spray-freeze drying rendered

  7. Mucosal immune response in broilers following vaccination with inactivated influenza and recombinant Bacillus subtilis

    Science.gov (United States)

    Mucosal and systemic immunity were observed in broilers vaccinated with mannosylated chitosan adjuvated (MCA) inactivated A/Turkey/Virginia/158512/2002 (H7N2) and administered with and without recombinant Bacillus subtilis to elicit heterologous influenza strain protection. Previously, mucosal immu...

  8. SAFETY OF INACTIVATED POLYMER-SUBUNIT THREE VALENCE INFLUENZA VACCINE. POSTREGISTRATIONAL OBSERVATION

    Directory of Open Access Journals (Sweden)

    S.M. Kharit

    2009-01-01

    Full Text Available Clinical trial for polymer-subunit trivalent influenza vaccine Grippol plus reactogenicity assessment in 153 children aged 3–17 years old was conducted in the frames of post-registration studies. Prior to the vaccination the written informed agreement was signed by every participant’ parent. In post-vaccination period physical examination and thermometry was performed daily in post-immunization days 1–5, on days 21–28 and then on a monthly basis for 4 months. Study results demonstrated that Grippol plus possesses low reactogenicity and can be applied in pediatrics for immunization in accordance with National Immunization schedule.Key words: children, influenza, vaccination.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2009;8(4:37-41

  9. Intranasal Immunization with Pressure Inactivated Avian Influenza Elicits Cellular and Humoral Responses in Mice.

    Directory of Open Access Journals (Sweden)

    Shana P C Barroso

    Full Text Available Influenza viruses pose a serious global health threat, particularly in light of newly emerging strains, such as the avian influenza H5N1 and H7N9 viruses. Vaccination remains the primary method for preventing acquiring influenza or for avoiding developing serious complications related to the disease. Vaccinations based on inactivated split virus vaccines or on chemically inactivated whole virus have some important drawbacks, including changes in the immunogenic properties of the virus. To induce a greater mucosal immune response, intranasally administered vaccines are highly desired as they not only prevent disease but can also block the infection at its primary site. To avoid these drawbacks, hydrostatic pressure has been used as a potential method for viral inactivation and vaccine production. In this study, we show that hydrostatic pressure inactivates the avian influenza A H3N8 virus, while still maintaining hemagglutinin and neuraminidase functionalities. Challenged vaccinated animals showed no disease signs (ruffled fur, lethargy, weight loss, and huddling. Similarly, these animals showed less Evans Blue dye leakage and lower cell counts in their bronchoalveolar lavage fluid compared with the challenged non-vaccinated group. We found that the whole inactivated particles were capable of generating a neutralizing antibody response in serum, and IgA was also found in nasal mucosa and feces. After the vaccination and challenge we observed Th1/Th2 cytokine secretion with a prevalence of IFN-γ. Our data indicate that the animals present a satisfactory immune response after vaccination and are protected against infection. Our results may pave the way for the development of a novel pressure-based vaccine against influenza virus.

  10. Heterosubtypic cross-protection induced by whole inactivated influenza virus vaccine in mice : Influence of the route of vaccine administration

    NARCIS (Netherlands)

    Budimir, Natalija; de Haan, Aalzen; Meijerhof, Tjarko; Gostick, Emma; Price, David A.; Huckriede, Anke; Wilschut, Jan

    2013-01-01

    Background Development of influenza vaccines capable of inducing broad protection against different virus subtypes is necessary given the ever-changing viral genetic landscape. Previously, we showed that vaccination with whole inactivated virus (WIV) induces heterosubtypic protection against lethal

  11. Inactivated influenza vaccines: recent progress and implications for the elderly.

    Science.gov (United States)

    Parodi, Valentina; de Florentiis, Daniela; Martini, Mariano; Ansaldi, Filippo

    2011-02-01

    The current public health strategy for the containment of influenza is annual vaccination, which is recommended for the elderly and for those in risk factor categories that present the highest morbidity and mortality. However, because the immune response in the elderly is known to be less vigorous than in younger adults, research in the last decade has focused on improving the immune response to vaccination and increasing the protection of aged populations. The decreased efficacy of vaccines in the elderly is due to several factors, such as a decrease in the number of Langerhans cells, the limited capacity of dendritic cells to present antigen, defects in the expression of Toll-like receptors and the reduced expression of MHC class I and II molecules. Also, production of mature naive T cells by the thymus decreases with age. Among several approaches proposed to address the need for more immunogenic vaccines compared with conventional agents, the most well proven is the use of adjuvants. The first licensed adjuvant, aluminium-based mineral salts (alum), introduced in the 1920s, remains the standard worldwide adjuvant for human use and it has been widely used for almost a century. However, the addition of alum adjuvant to a split or subunit influenza vaccine has induced only marginal improvements. Other adjuvants have been developed and approved for human use since 1997; in particular, MF59, an oil-in-water adjuvant emulsion of squalene, which is able to increase immunogenicity of seasonal, pre-pandemic and pandemic subunit vaccines while maintaining acceptable safety and tolerability profiles. More recently, another oil-in-water emulsion, AS03, has been approved as a component of pre-pandemic H5N1 and pandemic H1N1 2009 vaccines. Besides adjuvants, several other strategies have been assessed to enhance antibody response in the elderly and other less responsive subjects, such as high-dose antigen vaccines, carrier systems (liposomes/virosomes) and the intradermal

  12. A randomized clinical trial of an inactivated avian influenza A (H7N7 vaccine.

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    Robert B Couch

    Full Text Available BACKGROUND: Concern for a pandemic caused by a newly emerged avian influenza A virus has led to clinical trials with candidate vaccines as preparation for such an event. Most trials have involved vaccines for influenza A (H5N1, A (H7N7 or A (H9N2. OBJECTIVE: To evaluate dosage-related safety and immunogenicity of an inactivated influenza A (H7N7 vaccine in humans. DESIGN: One hundred twenty-five healthy young adults were randomized to receive two doses intramuscularly of placebo or 7.5, 15, 45 or 90 µg of HA of an inactivated subunit influenza A (H7N7 vaccine (25 per group, four weeks apart. Reactogenicity was evaluated closely for one week and for any adverse effect for six months after each dose. Serum hemagglutination-inhibiting and neutralizing antibody responses were determined four weeks after each dose and at six months. RESULTS: Reactogenicity evaluations indicated the vaccinations were well tolerated. Only one subject developed a ≥4-fold serum hemagglutination-inhibition (HAI antibody response and a final titer of ≥1:40 four weeks after dose two and only five subjects developed a neutralizing antibody rise and a final titer of ≥1:40 in tests performed at a central laboratory. Four of the five were given the 45 or 90 µg HA dosage. A more sensitive HAI assay at the study site revealed a dose-response with increasing HA dosage but only 36% in the 90 µg HA group developed a ≥4-fold rise in antibody in this test and only one of these achieved a titer of ≥1:32. CONCLUSION: This inactivated subunit influenza A (H7N7 vaccine was safe but poorly immunogenic in humans. TRIALS REGISTRATION: ClinicalTrials.gov NCT00546585.

  13. Safety, immunogenicity, and lot-to-lot consistency of a quadrivalent inactivated influenza vaccine in children, adolescents, and adults: A randomized, controlled, phase III trial.

    Science.gov (United States)

    Cadorna-Carlos, Josefina B; Nolan, Terry; Borja-Tabora, Charissa Fay; Santos, Jaime; Montalban, M Cecilia; de Looze, Ferdinandus J; Eizenberg, Peter; Hall, Stephen; Dupuy, Martin; Hutagalung, Yanee; Pépin, Stéphanie; Saville, Melanie

    2015-05-15

    Inactivated quadrivalent influenza vaccine (IIV4) containing two influenza A strains and one strain from each B lineage (Yamagata and Victoria) may offer broader protection against seasonal influenza than inactivated trivalent influenza vaccine (IIV3), containing a single B strain. This study examined the safety, immunogenicity, and lot consistency of an IIV4 candidate. This phase III, randomized, controlled, multicenter trial in children/adolescents (9 through 17 years) and adults (18 through 60 years) was conducted in Australia and in the Philippines in 2012. The study was double-blind for IIV4 lots and open-label for IIV4 vs IIV3. Children/adolescents were randomized 2:2:2:1 and adults 10:10:10:1 to receive one of three lots of IIV4 or licensed IIV3. Safety data were collected for up to 6 months post-vaccination. Hemagglutination inhibition and seroneutralization antibody titers were assessed pre-vaccination and 21 days post-vaccination. 1648 adults and 329 children/adolescents received IIV4, and 56 adults and 55 children/adolescents received IIV3. Solicited reactions, unsolicited adverse events, and serious adverse events were similar for IIV3 and IIV4 recipients in both age groups. Injection-site pain, headache, malaise, and myalgia were the most frequently reported solicited reactions, most of which were mild and resolved within 3 days. No vaccine-related serious adverse events or deaths were reported. Post-vaccination antibody responses, seroconversion rates, and seroprotection rates for the 3 strains common to both vaccines were comparable for IIV3 and IIV4 in both age groups. Antibody responses to IIV4 were equivalent among vaccine lots and comparable between age groups for each of the 4 strains. IIV4 met all European Medicines Agency immunogenicity criteria for adults for all 4 strains. In both age groups, IIV4 was well tolerated and caused no safety concerns, induced robust antibody responses to all 4 influenza strains, and met all EMA immunogenicity

  14. Poly I:C adjuvanted inactivated swine influenza vaccine induces heterologous protective immunity in pigs.

    Science.gov (United States)

    Thomas, Milton; Wang, Zhao; Sreenivasan, Chithra C; Hause, Ben M; Gourapura J Renukaradhya; Li, Feng; Francis, David H; Kaushik, Radhey S; Khatri, Mahesh

    2015-01-15

    Swine influenza is widely prevalent in swine herds in North America and Europe causing enormous economic losses and a public health threat. Pigs can be infected by both avian and mammalian influenza viruses and are sources of generation of reassortant influenza viruses capable of causing pandemics in humans. Current commercial vaccines provide satisfactory immunity against homologous viruses; however, protection against heterologous viruses is not adequate. In this study, we evaluated the protective efficacy of an intranasal Poly I:C adjuvanted UV inactivated bivalent swine influenza vaccine consisting of Swine/OH/24366/07 H1N1 and Swine/CO/99 H3N2, referred as PAV, in maternal antibody positive pigs against an antigenic variant and a heterologous swine influenza virus challenge. Groups of three-week-old commercial-grade pigs were immunized intranasally with PAV or a commercial vaccine (CV) twice at 2 weeks intervals. Three weeks after the second immunization, pigs were challenged with the antigenic variant Swine/MN/08 H1N1 (MN08) and the heterologous Swine/NC/10 H1N2 (NC10) influenza virus. Antibodies in serum and respiratory tract, lung lesions, virus shedding in nasal secretions and virus load in lungs were assessed. Intranasal administration of PAV induced challenge viruses specific-hemagglutination inhibition- and IgG antibodies in the serum and IgA and IgG antibodies in the respiratory tract. Importantly, intranasal administration of PAV provided protection against the antigenic variant MN08 and the heterologous NC10 swine influenza viruses as evidenced by significant reductions in lung virus load, gross lung lesions and significantly reduced shedding of challenge viruses in nasal secretions. These results indicate that Poly I:C or its homologues may be effective as vaccine adjuvants capable of generating cross-protective immunity against antigenic variants/heterologous swine influenza viruses in pigs. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Patients with humoral primary immunodeficiency do not develop protective anti-influenza antibody titers after vaccination with trivalent subunit influenza vaccine

    NARCIS (Netherlands)

    van Assen, Sander; Holvast, Albert; Telgt, Denise S.C.; Benne, Cornelis A.; de Haan, Aalzen; Westra, Johanna; Kallenberg, Cornelis; Bijl, Marc

    Yearly influenza vaccination is recommended for patients with humoral primary immunodeficiency (hPID). However, humoral responses following vaccination can be expected to be reduced in these patients.The efficacy of influenza vaccination in patients with hPID, anti-influenza antibody responses was

  16. Protective efficacy in mice of monovalent and trivalent live attenuated influenza vaccines in the background of cold-adapted A/X-31 and B/Lee/40 donor strains.

    Science.gov (United States)

    Jang, Yo Han; Lee, Eun-Young; Byun, Young Ho; Jung, Eun-Ju; Lee, Yoon Jae; Lee, Yun Ha; Lee, Kwang-Hee; Lee, Jinhee; Seong, Baik Lin

    2014-01-23

    Influenza virus continues to take a heavy toll on human health and vaccination remains the mainstay of efforts to reduce the clinical impact imposed by viral infections. Proven successful for establishing live attenuated vaccine donor strains, cold-adapted live attenuated influenza vaccines (CAIVs) have become an attractive modality for controlling the virus infection. Previously, we developed the cold-adapted strains A/X-31 and B/Lee/40 as novel donor strains of CAIVs against influenza A and B viruses. In this study, we investigated the protective immune responses of both mono- and trivalent vaccine formulations in the mouse model. Two type A vaccines and one type B vaccine against A/New Caledonia/20/99 (H1N1), A/Panama/2007/99 (H3N2), and B/Shangdong/7/97 in the background of the A/X-31 ca or B/Lee/40 ca were generated by a reassortment procedure and evaluated for their immunogenicity and protective efficacy. Each monovalent vaccine elicited high levels of serum antibodies and conferred complete protection against homologous wild type virus infection. As compared to the monovalent vaccines, trivalent formulation induced higher levels of type A-specific serum antibodies and slightly lower levels of type B-specific antibodies, suggesting an immunological synergism within type A viruses and an interference in the replication of type B virus. Relatively lower type B-specific immunogenicity in trivalent vaccine formulation could be effectively implemented by increasing the vaccine dose of influenza B virus. These results of immunogenicity, protection efficacy, and immunological synergism between type A vaccines provide an experimental basis for optimal composition of trivalent vaccines for subsequent developments of multivalent CAIVs against seasonal and pandemic influenza viruses. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Observational safety study of specific outcomes after trivalent cell culture seasonal influenza vaccination (Optaflu®) among adults in THIN database of electronic UK primary healthcare records.

    Science.gov (United States)

    Hall, Gillian C; Davies, Paul T G; Karim, M Yousuf; Haag, Mendel D M; O'Leary, Caroline

    2018-01-01

    To investigate the safety of trivalent seasonal influenza vaccine (TIVc) (Optaflu ® ), the first cell culture seasonal trivalent influenza vaccine available in Europe. Codes and unstructured text in adult electronic healthcare records (The Health Improvement Network) were searched for a TIVc brand name or batch number and possible outcomes within a 3 month pre- to 6 month post-TIVc exposure study period (2012-2015). The outcomes were severe allergic reactions, Bell's palsy, convulsions, demyelination, paresthesia, noninfectious encephalitis, neuritis (optic and brachial), vasculitis, inflammatory bowel disease, and thrombocytopenia. Risk periods were defined based on biologically plausible time frame postvaccination when an outcome caused by the vaccine might be expected to occur. Possible outcomes were adjudicated against outcome specific case definitions and a date of onset assigned by using electronic and other medical records. Observed (risk period) to expected (outside risk and preexposure periods) rate ratios, postexposure incidence, and plots of time from exposure to outcome were reported. Sixteen of 1011 events from 4578 exposures fulfilled a primary case definition and had a date of onset during the study period. Three were in observed time. The observed-to-expected rate ratios were (3.3, 95% CI 0.3, 31.7) for convulsions and (1.5, 95% CI 0.2, 14.9) for thrombocytopenia with 1 outcome each in observed time. There was 1 incident inflammatory bowel disease in observed, but none in expected, time. The small sample size restricts interpretation; however, no hypothesis of an increased risk of a study outcome was generated. Adjudication of events against case definitions to reduce misclassification of onset and outcomes allowed use of precise risk periods. KEY POINTS This observational study did not generate a hypothesis of an association between the first cell-culture seasonal influenza vaccination available in the European Union and any of the study

  18. Orthogonal inactivation of influenza and the creation of detergent resistant viral aggregates: towards a novel vaccine strategy

    Directory of Open Access Journals (Sweden)

    Belanger Julie M

    2012-03-01

    Full Text Available Abstract Background It has been previously shown that enveloped viruses can be inactivated using aryl azides, such as 1-iodo-5-azidonaphthalene (INA, plus UVA irradiation with preservation of surface epitopes in the inactivated virus preparations. Prolonged UVA irradiation in the presence of INA results in ROS-species formation, which in turn results in detergent resistant viral protein fractions. Results Herein, we characterize the applicability of this technique to inactivate influenza. It is shown that influenza virus + INA (100 micromolar + UVA irradiation for 30 minutes results in a significant (p Conclusion These orthogonally inactivated viral preparations with detergent resistant fractions are being explored as a novel route for safe, effective inactivated vaccines generated from a variety of enveloped viruses.

  19. Enhanced Stability of Inactivated Influenza Vaccine Encapsulated in Dissolving Microneedle Patches.

    Science.gov (United States)

    Chu, Leonard Y; Ye, Ling; Dong, Ke; Compans, Richard W; Yang, Chinglai; Prausnitz, Mark R

    2016-04-01

    This study tested the hypothesis that encapsulation of influenza vaccine in microneedle patches increases vaccine stability during storage at elevated temperature. Whole inactivated influenza virus vaccine (A/Puerto Rico/8/34) was formulated into dissolving microneedle patches and vaccine stability was evaluated by in vitro and in vivo assays of antigenicity and immunogenicity after storage for up to 3 months at 4, 25, 37 and 45°C. While liquid vaccine completely lost potency as determined by hemagglutination (HA) activity within 1-2 weeks outside of refrigeration, vaccine in microneedle patches lost 40-50% HA activity during or shortly after fabrication, but then had no significant additional loss of activity over 3 months of storage, independent of temperature. This level of stability required reduced humidity by packaging with desiccant, but was not affected by presence of oxygen. This finding was consistent with additional stability assays, including antigenicity of the vaccine measured by ELISA, virus particle morphological structure captured by transmission electron microscopy and protective immune responses by immunization of mice in vivo. These data show that inactivated influenza vaccine encapsulated in dissolving microneedle patches has enhanced stability during extended storage at elevated temperatures.

  20. Influenza vaccination type, live, attenuated influenza vaccine (LAIV) versus inactivated influenza vaccine (IIV), received by children, United States, 2011-12 through 2013-14 influenza seasons.

    Science.gov (United States)

    Kahn, Katherine E; Santibanez, Tammy A; Zhai, Yusheng; Singleton, James A

    2015-09-22

    Influenza vaccines available for children in the United States include inactivated influenza vaccine (IIV) and live, attenuated influenza vaccine (LAIV). Objectives of this study were to quantify proportions of IIV and LAIV received by vaccinated children, and examine associations between vaccine type received and demographic characteristics. National Immunization Survey-Flu (NIS-Flu) parental reported data for the 2011-12 through 2013-14 influenza seasons were used to estimate proportions of vaccinated children 2-17 years who received IIV and LAIV. Tests of association between vaccination type and demographic variables were conducted using Wald chi-square tests and pair-wise comparison t-tests. Multivariable logistic regression was used to determine variables independently associated with receipt of LAIV versus IIV. In the 2013-14 season, 33.3% of vaccinated children received LAIV, similar to the proportion in the 2011-12 (32.2%) and 2012-13 (32.1%) seasons. Across all seasons studied, the strongest observed association was between vaccination type and child's age, with children 2-8 years (Adjusted Prevalence Ratio (95% confidence interval) [APR(95% CI)] 1.41(1.27-1.56), 1.46(1.34-1.59), and 1.50(1.38-1.63) for 2011-12, 2012-13, and 2013-14) and 9-12 years (APR(95% CI) 1.37(1.23-1.54), 1.38(1.26-1.51), and 1.50(1.38-1.63) for 2011-12, 2012-13, and 2013-14) being more likely to have received LAIV than children 13-17 years. Among those vaccinated, whites were more likely to have received LAIV compared with blacks (APR(95% CI) 1.19(1.05-1.35), 1.24(1.10-1.39), and 1.22(1.11-1.34) for 2011-12, 2012-13, and 2013-14), and children living above poverty (annual income >$75,000) were more likely to have received LAIV than those living at or below poverty (APR(95% CI) 1.43(1.23-1.67), 1.13(1.02-1.26), and 1.16(1.06-1.28) for 2011-12, 2012-13, and 2013-14). This study provides a baseline of the extent and patterns of LAIV uptake that can be used to measure the impact of

  1. SAFETY AND EFFICIENCY OF INACTIVATED OF SUBUNIT INFLUENZA VACCINE AT MASS VACCINATION OF CHILDREN

    Directory of Open Access Journals (Sweden)

    Yu.Z. Gendon

    2007-01-01

    Full Text Available The article considers the results of infantile mass vaccination with inactivated subunit influenza vaccine (Influvac. It shows that vaccination of 57–72% of children aged 3–17 from organized collectives residing in Mytishchi and Orekhovoczuevo districts of Moscow region was accompanied with nearly triple reduce of flu rates vs. Narofominsk and Odintsovo districts where vaccination was occasional (< 1% of children. The efficiency of the vaccination made 63,7%. Low reactogenicity of the influenza vaccine was recorded. Its convenient packing allows vaccination of large number of children in a short time. The article justifies the necessity of yearly vaccinations even in case of similarity of flu virus strain.Key words: children, mass vaccination, subunit flu vaccine, safety.

  2. Enhanced pulmonary immunization with aerosolized inactivated influenza vaccine containing delta inulin adjuvant.

    Science.gov (United States)

    Murugappan, Senthil; Frijlink, Henderik W; Petrovsky, Nikolai; Hinrichs, Wouter L J

    2015-01-23

    Vaccination is the primary intervention to contain influenza virus spread during seasonal and pandemic outbreaks. Pulmonary vaccination is gaining increasing attention for its ability to induce both local mucosal and systemic immune responses without the need for invasive injections. However, pulmonary administration of whole inactivated influenza virus (WIV) vaccine induces a Th2 dominant systemic immune response while a more balanced Th1/Th2 vaccine response may be preferred and only induces modest nasal immunity. This study evaluated immunity elicited by pulmonary versus intramuscular (i.m.) delivery of WIV, and tested whether the immune response could be improved by co-administration of delta (δ)-inulin, a novel carbohydrate-based particulate adjuvant. After pulmonary administration both unadjuvanted and δ-inulin adjuvanted WIV induced a potent systemic immune response, inducing higher serum anti-influenza IgG titers and nasal IgA titers than i.m. administration. Moreover, the addition of δ-inulin induced a more balanced Th1/Th2 response and induced higher nasal IgA titers versus pulmonary WIV alone. Pulmonary WIV alone or with δ-inulin induced hemagglutination inhibition (HI) titers>40, titers which are considered protective against influenza virus. In conclusion, in this study we have shown that δ-inulin adjuvanted WIV induces a better immune response after pulmonary administration than vaccine alone. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. The comparative value of various employer-sponsored influenza vaccination clinics.

    Science.gov (United States)

    Zimmerman, Richard K; Wiringa, Ann E; Nowalk, Mary Patricia; Lin, Chyongchiou J; Rousculp, Matthew D; Mitgang, Elizabeth A; Lee, Bruce Y

    2012-09-01

    Many US firms offer influenza vaccination clinics to prevent lost productivity due to influenza. Strategies to promote and offer vaccination differ, and the economic value of the strategies is unknown. Decision analytic modeling and Monte Carlo probabilistic sensitivity analyses estimated the one-season cost-consequences of three types of influenza clinics (trivalent inactivated influenza vaccine only, vaccine choice [trivalent inactivated influenza or intranasal {live attenuated influenza} vaccine], or vaccine choice plus incentive) in firms of 50 and 250 employees, from the employer's perspective. On-site influenza vaccination was generally cost-saving over no vaccination. For the scenario of vaccine effectiveness of 70% and intermediate transmissibility, the incremental costs per employee for a firm of 50 employees were -$6.41 (ie, cost savings) for inactivated vaccine only versus no vaccination, -$1.48 for vaccine choice versus inactivated vaccine, and $1.84 for vaccine choice plus incentive versus vaccine choice. Clinics offering a choice of vaccines were slightly less costly under many scenarios. Generally, incremental costs were lower (1) in larger firms; (2) when influenza was assumed to be more contagious; and (3) when vaccine effectiveness was assumed to be higher. Employer-sponsored influenza vaccination clinics are generally cost-saving.

  4. Evaluation of different inactivation methods for high and low pathogenic avian influenza viruses in egg-fluids for antigen preparation.

    Science.gov (United States)

    Pawar, Shailesh D; Murtadak, Vinay B; Kale, Sandeep D; Shinde, Prashant V; Parkhi, Saurabh S

    2015-09-15

    In view of the emerging avian influenza (AI) viruses, it is important to study the susceptibility of AI viruses to inactivating agents for preparation of antigens and inactivated vaccines. The available information on susceptibility of both the high and low pathogenic AI viruses to different inactivating agents is inadequate and ambiguous. It has been shown that different subtypes of influenza viruses require different physical and chemical conditions for inactivation of infectivity. The present study was undertaken to evaluate the use of beta-propiolactone (BPL), formalin and ether for inactivation and its impact on antigenicity of AI viruses. A total of nine high and low pathogenic AI viruses belonging to four influenza A subtypes were included in the study. The H5N1 viruses were from the clades 2.2, 2.3.2.1 and 2.3.4. The H9N2 virus included in the study was of the G1 genotype, while the H11N1 and H4N6 viruses were from the Eurasian lineage. The viruses were treated with BPL, formalin and with ether. The confirmation of virus inactivation was performed by two serial passages of inactivated viruses in embryonated chicken eggs. The infectivity of all tested AI viruses was eliminated using 0.1% BPL and 0.1% formalin. Ether eliminated infectivity of all tested low pathogenic AI viruses; however, ether with 0.2% or 0.5% Tween-20 was required for inactivation of the highly pathogenic AI H5N1 viruses. Treatment with BPL, ether and formalin retained virus hemagglutination (HA) titers. Interestingly ether treatment resulted in significant rise in HA titers (Pviruses. This data demonstrated the utility of BPL, formalin and ether for the inactivation of infectivity of AI viruses used in the study for the preparation of inactivated virus antigens for research and diagnosis of AI. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Immune responses elicited to a live-attenuated influenza virus vaccine compared to a traditional whole-inactivated virus vaccine for pandemic H1N1in pigs

    Science.gov (United States)

    In the United States there are currently two influenza vaccine platforms approved for use in humans - conventional inactivated virus and live-attenuated influenza virus (LAIV). One of the major challenges for influenza vaccination is designing a platform that provides cross-protection across strains...

  6. Reduction of high pathogenicity avian influenza virus in eggs from chickens once or twice vaccinated with an oil-emulsified inactivated H5 avian influenza vaccine

    Science.gov (United States)

    The negative impact of high pathogenicity avian influenza virus (HPAIV) infection on egg production and deposition of virus in eggs, as well as any protective effect of vaccination, is unknown. Individually housed non-vaccinated, sham-vaccinated and inactivated H5N9 vaccinated once or twice adult Wh...

  7. Detection and characterization of influenza A virus endemic circulation in neonatal and nursery pigs in a farm using an inactivated influenza vaccine

    Science.gov (United States)

    Influenza A virus (IAV) is the cause of an acute respiratory disease affecting swine worldwide with potential zoonotic implications. Inactivated IAV vaccines used in breeding females provides passive immunity to neonatal piglets through colostrum. However, maternally derived antibody (MDA) may reduc...

  8. Simplifying influenza vaccination during pandemics: sublingual priming and intramuscular boosting of immune responses with heterologous whole inactivated influenza vaccine.

    Science.gov (United States)

    Murugappan, Senthil; Patil, Harshad P; Frijlink, Henderik W; Huckriede, Anke; Hinrichs, Wouter L J

    2014-03-01

    The best approach to control the spread of influenza virus during a pandemic is vaccination. Yet, an appropriate vaccine is not available early in the pandemic since vaccine production is time consuming. For influenza strains with a high pandemic potential like H5N1, stockpiling of vaccines has been considered but is hampered by rapid antigenic drift of the virus. It has, however, been shown that immunization with a given H5N1 strain can prime the immune system for a later booster with a drifted variant. Here, we investigated whether whole inactivated virus (WIV) vaccine can be processed to tablets suitable for sublingual (s.l.) use and whether s.l. vaccine administration can prime the immune system for a later intramuscular (i.m.) boost with a heterologous vaccine. In vitro results demonstrate that freeze-drying and tableting of WIV did not affect the integrity of the viral proteins or the hemagglutinating properties of the viral particles. Immunization experiments revealed that s.l. priming with WIV (prepared from the H5N1 vaccine strain NIBRG-14) 4 weeks prior to i.m. booster immunization with the same virus strongly enhanced hemagglutination-inhibition (HI) titers against NIBRG-14 and the drifted variant NIBRG-23. Moreover, s.l. (and i.m.) immunization with NIBRG-14 also primed for a subsequent heterologous i.m. booster immunization with NIBRG-23 vaccine. In addition to HI serum antibodies, s.l. priming enhanced lung and nose IgA responses, while i.m. priming enhanced lung IgA but not nose IgA levels. Our results identify s.l. vaccination as a user-friendly method to prime for influenza-specific immune responses toward homologous and drifted variants.

  9. Potency determination of inactivated H7 influenza vaccines using monoclonal antibody-based ELISA and biolayer interferometry assays.

    Science.gov (United States)

    Vasudevan, Anupama; Woerner, Amy; Schmeisser, Falko; Verma, Swati; Williams, Ollie; Weir, Jerry P

    2018-03-01

    The single radial immunodiffusion (SRID) assay, the accepted method for determining potency of inactivated influenza vaccines, measures an immunogenic form of the influenza hemagglutinin. Nevertheless, alternative methods for measuring vaccine potency have been explored to address some of the weaknesses of the SRID assay, including limited sensitivity and the requirement for large amounts of standardized reagents. Monoclonal antibody (mAb)-based potency assays also have the ability to detect and measure relevant immunogenic forms of HA. The objective of this study was to continue evaluation of mAb-based alternative methods for measuring the potency of inactivated influenza vaccines, focusing on A(H7N9) pandemic influenza vaccines. Several murine mAbs that recognize different epitopes on the H7 hemagglutinin (HA) were identified and characterized. These mAbs were evaluated in both a mAb-capture ELISA and a mAb-based biolayer interferometry (BLI) assay. Results indicated that potency of inactivated A(H7N9) vaccines, including vaccine samples that were stressed by heat treatment, measured by either alternative method correlated well with potency determined by the traditional SRID potency assay. The availability of multiple H7 mAbs, directed to different HA epitopes, provides needed redundancy in the potency analysis as A(H7N9) viruses continue to evolve antigenically and suggests the importance of having a broad, well-characterized panel of mAbs available for development of vaccines against influenza strains with pandemic potential. In addition, the results highlight the potential of mAb-based platform such as ELISA and BLI for development as alternative methods for determining the potency of inactivated influenza vaccines. Published 2017. This article is a U.S. Government work and is in the public domain in the USA. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.

  10. Effect of Osmotic Pressure on the Stability of Whole Inactivated Influenza Vaccine for Coating on Microneedles.

    Directory of Open Access Journals (Sweden)

    Hyo-Jick Choi

    Full Text Available Enveloped virus vaccines can be damaged by high osmotic strength solutions, such as those used to protect the vaccine antigen during drying, which contain high concentrations of sugars. We therefore studied shrinkage and activity loss of whole inactivated influenza virus in hyperosmotic solutions and used those findings to improve vaccine coating of microneedle patches for influenza vaccination. Using stopped-flow light scattering analysis, we found that the virus underwent an initial shrinkage on the order of 10% by volume within 5 s upon exposure to a hyperosmotic stress difference of 217 milliosmolarity. During this shrinkage, the virus envelope had very low osmotic water permeability (1 - 6×10-4 cm s-1 and high Arrhenius activation energy (Ea = 15.0 kcal mol-1, indicating that the water molecules diffused through the viral lipid membranes. After a quasi-stable state of approximately 20 s to 2 min, depending on the species and hypertonic osmotic strength difference of disaccharides, there was a second phase of viral shrinkage. At the highest osmotic strengths, this led to an undulating light scattering profile that appeared to be related to perturbation of the viral envelope resulting in loss of virus activity, as determined by in vitro hemagglutination measurements and in vivo immunogenicity studies in mice. Addition of carboxymethyl cellulose effectively prevented vaccine activity loss in vitro and in vivo, believed to be due to increasing the viscosity of concentrated sugar solution and thereby reducing osmotic stress during coating of microneedles. These results suggest that hyperosmotic solutions can cause biphasic shrinkage of whole inactivated influenza virus which can damage vaccine activity at high osmotic strength and that addition of a viscosity enhancer to the vaccine coating solution can prevent osmotically driven damage and thereby enable preparation of stable microneedle coating formulations for vaccination.

  11. A mechanistic study on the destabilization of whole inactivated influenza virus vaccine in gastric environment.

    Science.gov (United States)

    Choi, Hyo-Jick; Ebersbacher, Charles F; Kim, Min-Chul; Kang, Sang-Moo; Montemagno, Carlo D

    2013-01-01

    Oral immunization using whole inactivated influenza virus vaccine promises an efficient vaccination strategy. While oral vaccination was hampered by harsh gastric environment, a systematic understanding about vaccine destabilization mechanisms was not performed. Here, we investigated the separate and combined effects of temperature, retention time, pH, and osmotic stress on the stability of influenza vaccine by monitoring the time-dependent morphological change using stopped-flow light scattering. When exposed to osmotic stress, clustering of vaccine particles was enhanced in an acidic medium (pH 2.0) at ≥25°C. Fluorescence spectroscopic studies showed that hyper-osmotic stress at pH 2.0 and 37°C caused a considerable increase in conformational change of antigenic proteins compared to that in acidic iso-osmotic medium. A structural integrity of membrane was destroyed upon exposure to hyper-osmotic stress, leading to irreversible morphological change, as observed by undulation in stopped-flow light scattering intensity and transmission electron microscopy. Consistent with these analyses, hemagglutination activity decreased more significantly with an increasing magnitude of hyper-osmotic stress than in the presence of the hypo- and iso-osmotic stresses. This study shows that the magnitude and direction of the osmotic gradient has a substantial impact on the stability of orally administrated influenza vaccine.

  12. A mechanistic study on the destabilization of whole inactivated influenza virus vaccine in gastric environment.

    Directory of Open Access Journals (Sweden)

    Hyo-Jick Choi

    Full Text Available Oral immunization using whole inactivated influenza virus vaccine promises an efficient vaccination strategy. While oral vaccination was hampered by harsh gastric environment, a systematic understanding about vaccine destabilization mechanisms was not performed. Here, we investigated the separate and combined effects of temperature, retention time, pH, and osmotic stress on the stability of influenza vaccine by monitoring the time-dependent morphological change using stopped-flow light scattering. When exposed to osmotic stress, clustering of vaccine particles was enhanced in an acidic medium (pH 2.0 at ≥25°C. Fluorescence spectroscopic studies showed that hyper-osmotic stress at pH 2.0 and 37°C caused a considerable increase in conformational change of antigenic proteins compared to that in acidic iso-osmotic medium. A structural integrity of membrane was destroyed upon exposure to hyper-osmotic stress, leading to irreversible morphological change, as observed by undulation in stopped-flow light scattering intensity and transmission electron microscopy. Consistent with these analyses, hemagglutination activity decreased more significantly with an increasing magnitude of hyper-osmotic stress than in the presence of the hypo- and iso-osmotic stresses. This study shows that the magnitude and direction of the osmotic gradient has a substantial impact on the stability of orally administrated influenza vaccine.

  13. Influenza immunization during pregnancy: Benefits for mother and infant.

    Science.gov (United States)

    Sakala, Isaac G; Honda-Okubo, Yoshikazu; Fung, Johnson; Petrovsky, Nikolai

    2016-12-01

    The serious consequences of influenza infection during pregnancy have been recognized for almost a century. In this article, we reviewed the evidence on the immunogenicity, safety and impact of maternal influenza immunization for both mother and child. After vaccination, pregnant women have similar protective titers of anti-influenza antibodies as non-pregnant women, demonstrating that pregnancy does not alter the trivalent inactivated influenza vaccine immune response. Studies from the United States, Europe and resource-constrained regions demonstrate that maternal vaccination is associated with increased anti-influenza antibody concentrations and protection in the newborn child as well as the immunized mother. Given the acceptable safety profile of influenza vaccines and the World Health Organization's recommendation for its use in pregnant women, maternal vaccination with inactivated influenza vaccine is a cost-effective approach to decrease influenza disease in newborns. However, as seen for influenza immunization in the elderly, the protective efficacy of current inactivated vaccines in protection of newborns is 50% at best, indicating significant room for vaccine improvement, which could potentially be achieved by addition of a safe and effective adjuvant. Thus, global deployment of inactivated influenza immunization during pregnancy would have substantial and measurable health benefits for mothers and their newborns.

  14. Risk of Febrile Seizures and Epilepsy After Vaccination With Diphtheria, Tetanus, Acellular Pertussis, Inactivated Poliovirus, and Haemophilus Influenzae Type b

    DEFF Research Database (Denmark)

    Sun, Yuelian; Christensen, Jakob Christensen; Hviid, Anders

    2012-01-01

    -acellular pertussis–inactivated poliovirus– Haemophilus influenzae type b (DTaP-IPV-Hib) vaccine since September 2002. Objective To estimate the risk of febrile seizures and epilepsy after DTaP-IPV-Hib vaccination given at 3, 5, and 12 months. Design, Setting, and Participants A population-based cohort study of 378...

  15. Serological response to vaccination against avian influenza in zoo-birds using an inactivated H5N9 vaccine

    DEFF Research Database (Denmark)

    Bertelsen, Mads F.; Klausen, Joan; Holm, Elisabeth

    2007-01-01

    Five hundred and forty birds in three zoos were vaccinated twice against avian influenza with a 6-week interval using an inactivated H5N9 vaccine. Serological response was evaluated by hemagglutination inhibition test 4-6 weeks following the second vaccine administration. 84% of the birds...

  16. Comparison of adjuvants for a spray freeze-dried whole inactivated virus influenza vaccine for pulmonary administration

    NARCIS (Netherlands)

    Patil, Harshad P.; Murugappan, Senthil; de Vries-Idema, Jacobje; Meijerhof, Tjarko; de Haan, Aalzen; Frijlink, Henderik W.; Wilschut, Jan; Hinrichs, Wouter L. J.; Huckriede, Anke

    Stable vaccines administered to the lungs by inhalation could circumvent many of the problems associated with current immunizations against respiratory infections. We earlier provided proof of concept in mice that pulmonary delivered whole inactivated virus (WIV) influenza vaccine formulated as a

  17. An analysis of national target groups for monovalent 2009 pandemic influenza vaccine and trivalent seasonal influenza vaccines in 2009-10 and 2010-11

    Directory of Open Access Journals (Sweden)

    Lee Esther ST

    2011-08-01

    Full Text Available Abstract Background Vaccination is generally considered to be the best primary prevention measure against influenza virus infection. Many countries encourage specific target groups of people to undertake vaccination, often with financial subsidies or a priority list. To understand differential patterns of national target groups for influenza vaccination before, during and after the 2009 influenza pandemic, we reviewed and analyzed the country-specific policies in the corresponding time periods. Methods Information on prioritized groups targeted to receive seasonal and pandemic influenza vaccines was derived from a multi-step internet search of official health department websites, press releases, media sources and academic journal articles. We assessed the frequency and consistency of targeting 20 different groups within populations which are associated with age, underlying medical conditions, role or occupations among different countries and vaccines. Information on subsidies provided to specific target groups was also extracted. Results We analyzed target groups for 33 (seasonal 2009 and 2009-10 vaccines, 72 (monovalent pandemic 2009-10 vaccine and 34 (seasonal 2010 and 2010-11 vaccines countries. In 2009-10, the elderly, those with chronic illness and health care workers were common targets for the seasonal vaccine. Comparatively, the elderly, care home residents and workers, animal contacts and close contacts were less frequently targeted to receive the pandemic vaccine. Pregnant women, obese persons, essential community workers and health care workers, however, were more commonly targeted. After the pandemic, pregnant women, obese persons, health care and care home workers, and close contacts were more commonly targeted to receive the seasonal vaccine compared to 2009-10, showing continued influence from the pandemic. Many of the countries provided free vaccines, partial subsidies, reimbursements or national health insurance coverage to

  18. Asthma exacerbations among asthmatic children receiving live attenuated versus inactivated influenza vaccines.

    Science.gov (United States)

    Ray, G Thomas; Lewis, Ned; Goddard, Kristin; Ross, Pat; Duffy, Jonathan; DeStefano, Frank; Baxter, Roger; Klein, Nicola P

    2017-05-09

    To investigate whether there is a difference in the risk of asthma exacerbations between children with pre-existing asthma who receive live attenuated influenza vaccine (LAIV) compared with inactivated influenza vaccine (IIV). We identified IIV and LAIV immunizations occurring between July 1, 2007 and March 31, 2014 among Kaiser Permanente Northern California members aged 2 to vaccinated asthmatic children, the OR of an inpatient/ED asthma exacerbation was 0.97 (95% CI: 0.82-1.15). Among LAIV-vaccinated asthmatic children the OR was 0.38 (95% CI: 0.17-0.90). In the difference-in-differences analysis, the odds of asthma exacerbation following LAIV were less than IIV (Ratio of ORs: 0.40, CI: 0.17-0.95, p value: 0.04). Among children ≥2years old with asthma, we found no increased risk of asthma exacerbation following LAIV or IIV, and a decreased risk following LAIV compared to IIV. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Influence of virus strain and antigen mass on efficacy of H5 avian influenza inactivated vaccines.

    Science.gov (United States)

    Swayne, D E; Beck, J R; Garcia, M; Stone, H D

    1999-06-01

    The influence of vaccine strain and antigen mass on the ability of inactivated avian influenza (AI) viruses to protect chicks from a lethal, highly pathogenic (HP) AI virus challenge was studied. Groups of 4-week-old chickens were immunized with inactivated vaccines containing one of 10 haemagglutinin subtype H5 AI viruses, one heterologous H7 AI virus or normal allantoic fluid (sham), and challenged 3 weeks later by intra-nasal inoculation with a HP H5 chicken-origin AI virus. All 10 H5 vaccines provided good protection from clinical signs and death, and produced positive serological reactions on agar gel immunodiffusion and haemagglutination inhibition tests. In experiment 1, challenge virus was recovered from the oropharynx of 80% of chickens in the H5 vaccine group. In five H5 vaccine groups, challenge virus was not recovered from the cloaca of chickens. In the other five H5 vaccine groups, the number of chickens with detection of challenge virus from the cloaca was lower than in the sham group (P turkey/Wisconsin/68 (H5N9) was the best vaccine candidate of the H5 strains tested (PD50= 0.006 μg AI antigen). These data demonstrate that chickens vaccinated with inactivated H5 whole virus AI vaccines were protected from clinical signs and death, but usage of vaccine generally did not prevent infection by the challenge virus, as indicated by recovery of virus from the oropharynx. Vaccine use reduced cloacal detection rates, and quantity of virus shed from the cloaca and oropharynx in some vaccine groups, which would potentially reduce environmental contamination and disease transmission in the field.

  20. Effectiveness of live attenuated influenza vaccine and inactivated influenza vaccine in children 2-17 years of age in 2013-2014 in the United States.

    Science.gov (United States)

    Caspard, Herve; Gaglani, Manjusha; Clipper, Lydia; Belongia, Edward A; McLean, Huong Q; Griffin, Marie R; Talbot, H Keipp; Poehling, Katherine A; Peters, Timothy R; Veney, Naomi; Ambrose, Christopher S

    2016-01-02

    A postmarketing observational study was initiated to evaluate quadrivalent live attenuated influenza vaccine (LAIV) effectiveness in children aged 2-17 years in the United States. Children and adolescents aged 2-17 years seeking outpatient care for febrile acute respiratory illness Vaccination status was documented from medical records or immunization registries. Children who received ≥1 dose of influenza vaccine ≥14 days before study visit were considered vaccinated. Vaccine effectiveness (VE) was estimated as 100×(1-adjusted odds ratio), where the odds of interest are the odds of vaccine exposure among influenza cases and test-negative controls. In total, 1033 children and adolescents were included in the analysis. Influenza was detected in 14% (145/1033) of all children, with 74% (108/145) of the influenza cases due to A/H1N1pdm09 strains, 21% (31) to influenza B, and 4% (6) to influenza H3N2. LAIV did not show significant effectiveness against A/H1N1pdm09 (VE 13% [95% CI: -55 to 51]) but was effective against B/Yamagata strains (82% [95% CI: 12-96]). Inactivated influenza vaccine was effective against A/H1N1pdm09 (74% [95% CI: 50-86]) and B/Yamagata (70% [95% CI: 18-89]). LAIV provided significant protection against B/Yamagata influenza but not against A/H1N1pdm09 in children aged 2-17 years in 2013-2014, resulting in a proposed change of the 2015-2016 formulation with a new and more heat-stable A/H1N1pdm09 LAIV strain. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Divergent immune responses and disease outcomes in piglets immunized with inactivated and attenuated H3N2 swine influenza vaccines in the presence of maternally-derived antibodies

    Science.gov (United States)

    Vaccine-associated enhanced respiratory disease (VAERD) can occur in pigs immunized with whole-inactivated influenza virus (WIV) vaccine and subsequently infected with an antigenically divergent virus of the same HA subtype. Live-attenuated influenza virus (LAIV) vaccines administered intranasally h...

  2. Inactivated H7 Influenza Virus Vaccines Protect Mice despite Inducing Only Low Levels of Neutralizing Antibodies.

    Science.gov (United States)

    Kamal, Ram P; Blanchfield, Kristy; Belser, Jessica A; Music, Nedzad; Tzeng, Wen-Pin; Holiday, Crystal; Burroughs, Ashley; Sun, Xiangjie; Maines, Taronna R; Levine, Min Z; York, Ian A

    2017-10-15

    Avian influenza viruses of the H7 hemagglutinin (HA) subtype present a significant public health threat, as evidenced by the ongoing outbreak of human A(H7N9) infections in China. When evaluated by hemagglutination inhibition (HI) and microneutralization (MN) assays, H7 viruses and vaccines are found to induce lower level of neutralizing antibodies (nAb) than do their seasonal counterparts, making it difficult to develop and evaluate prepandemic vaccines. We have previously shown that purified recombinant H7 HA appear to be poorly immunogenic in that they induce low levels of HI and MN antibodies. In this study, we immunized mice with whole inactivated reverse genetics reassortant (RG) viruses expressing HA and neuraminidase (NA) from 3 different H7 viruses [A/Shanghai/2/2013(H7N9), A/Netherlands/219/2003(H7N7), and A/New York/107/2003(H7N2)] or with human A(H1N1)pdm09 (A/California/07/2009-like) or A(H3N2) (A/Perth16/2009) viruses. Mice produced equivalent titers of antibodies to all viruses as measured by enzyme-linked immunosorbent assay (ELISA). However, the antibody titers induced by H7 viruses were significantly lower when measured by HI and MN assays. Despite inducing very low levels of nAb, H7 vaccines conferred complete protection against homologous virus challenge in mice, and the serum antibodies directed against the HA head region were capable of mediating protection. The apparently low immunogenicity associated with H7 viruses and vaccines may be at least partly related to measuring antibody titers with the traditional HI and MN assays, which may not provide a true measure of protective immunity associated with H7 immunization. This study underscores the need for development of additional correlates of protection for prepandemic vaccines. IMPORTANCE H7 avian influenza viruses present a serious risk to human health. Preparedness efforts include development of prepandemic vaccines. For seasonal influenza viruses, protection is correlated with antibody

  3. Oxygen-independent inactivation of Haemophilus influenzae transforming DNA monochromatic radiation: action spectrum, effect of histidine and repair

    International Nuclear Information System (INIS)

    Cabrera-Juarez, E.; Setlow, J.K.; Swenson, P.A.; Peak, M.J.

    1976-01-01

    The action spectrum for the oxygen-independent inactivation of native transforming DNA from Haemophilus influenzae with near-UV radiation revealed a shoulder beginning at 334 and extending to 460 nm. The presence of 0.2 M histidine during irradiation produced a small increase in inactivation at 254, 290 and 313 nm, a large increase at 334 nm and a decrease in activation at 365, 405 and 460 nm. Photoreactivation did not reverse the DNA damage produced at pH 7.0 at 334, 365, 405 and 460 nm, but did reactivate the DNA after irradiation at 254, 290 and 313 nm. The inactivation of DNA irradiated at 254, 290 and 313 nm was considerably greater when the transforming ability was assayed in an excision-defective mutant compared with the wild type, although DNA irradiated at 334, 365, 405 and 460 nm showed smaller differences. These results suggest that the oxygen-independent inactivation of H.influenzae DNA at pH 7 by irradiation at 334, 365, 405 and 460 nm is caused by lesions other than pyrimidine dimers. (author)

  4. Comparison of the influenza virus-specific effector and memory B-cell responses to immunization of children and adults with live attenuated or inactivated influenza virus vaccines.

    Science.gov (United States)

    Sasaki, Sanae; Jaimes, Maria C; Holmes, Tyson H; Dekker, Cornelia L; Mahmood, Kutubuddin; Kemble, George W; Arvin, Ann M; Greenberg, Harry B

    2007-01-01

    Cellular immune responses to influenza virus infection and influenza virus vaccination have not been rigorously characterized. We quantified the effector and memory B-cell responses in children and adults after administration of either live attenuated (LAIV) or inactivated (TIV) influenza virus vaccines and compared these to antibody responses. Peripheral blood mononuclear cells were collected at days 0, 7 to 12, and 27 to 42 after immunization of younger children (6 months to 4 years old), older children (5 to 9 years old), and adults. Influenza virus-specific effector immunoglobulin A (IgA) and IgG circulating antibody-secreting cells (ASC) and stimulated memory B cells were detected using an enzyme-linked immunospot assay. Circulating influenza virus-specific IgG and IgA ASC were detected 7 to 12 days after TIV and after LAIV immunization. Seventy-nine percent or more of adults and older children had demonstrable IgG ASC responses, while IgA ASC responses were detected in 29 to 53% of the subjects. The IgG ASC response rate to LAIV immunization in adults was significantly higher than the response rate measured by standard serum antibody assays (26.3% and 15.8% by neutralization and hemagglutination inhibition assays, respectively). IgG ASC and serum antibody responses were relatively low in the younger children compared to older children and adults. TIV, but not LAIV, significantly increased the percentage of circulating influenza virus-specific memory B cells detected at 27 to 42 days after immunization in children and adults. In conclusion, although both influenza vaccines are effective, we found significant differences in the B-cell and antibody responses elicited after LAIV or TIV immunization in adults and older children and between young children and older age groups.

  5. Emulsified nanoparticles containing inactivated influenza virus and CpG oligodeoxynucleotides critically influences the host immune responses in mice.

    Directory of Open Access Journals (Sweden)

    Ming-Hsi Huang

    2010-08-01

    Full Text Available Antigen sparing and cross-protective immunity are regarded as crucial in pandemic influenza vaccine development. Both targets can be achieved by adjuvantation strategy to elicit a robust and broadened immune response. We assessed the immunogenicity of an inactivated H5N1 whole-virion vaccine (A/Vietnam/1194/2004 NIBRG-14, clade 1 formulated with emulsified nanoparticles and investigated whether it can induce cross-clade protecting immunity.After formulation with PELC, a proprietary water-in-oil-in-water nanoemulsion comprising of bioresorbable polymer/Span(R85/squalene, inactivated virus was intramuscularly administered to mice in either one-dose or two-dose schedule. We found that the antigen-specific serum antibody responses elicited after two doses of non-adjuvanted vaccine were lower than those observed after a single dose of adjuvanted vaccine, PELC and the conventional alum adjuvant as well. Moreover, 5 microg HA of PELC-formulated inactivated virus were capable of inducing higher antibodies than those obtained from alum-adjuvanted vaccine. In single-dose study, we found that encapsulating inactivated virus into emulsified PELC nanoparticles could induce better antibody responses than those formulated with PELC-adsorbed vaccine. However, the potency was rather reduced when the inactivated virus and CpG (an immunostimulatory oligodeoxynucleotide containing unmethylated cytosine-guanosine motifs were co-encapsulated within the emulsion. Finally, the mice who received PELC/CpG(adsorption-vaccine could easily and quickly reach 100% of seroprotection against a homologous virus strain and effective cross-protection against a heterologous virus strain (A/Whooper swan/Mongolia/244/2005, clade 2.2.Encapsulating inactivated H5N1 influenza virus and CpG into emulsified nanoparticles critically influences the humoral responses against pandemic influenza. These results demonstrated that the use of PELC could be as antigen-sparing in preparation for a

  6. Survival of H5N1 influenza virus in water and its inactivation by chemical methods.

    Science.gov (United States)

    Mihai, Maria Elena; Tecu, Cristina; Ivanciuc, Alina Elena; Necula, Gheorghe; Lupulescu, Emilia; Onu, Adrian

    2011-01-01

    The ability of H5N1 Avian Influenza Virus (AIV) to survive in surface water has been assessed in experimental laboratory conditions, based on non-pathogenic avian reassortant model, by titration of infectivity (TCID50) at different time intervals, in three different types of water. The effect of different chemicals on AIV's survival was assessed using the same type of experimental model. After exposure to the chemical, followed by growth on a suitable substrate, the AIV was quantified by a real-time quantitative reverse transcriptase PCR (qRT-PCR). The reassortant virus persisted, and remained infective in aquatic environments, for 12 days at 22-35 degrees C and up to 20 days at 4 degrees C, irrespective of the type of water, supporting the hypothesis of a potential risk for transmitting the virus among birds and contaminating the household water via common sources of water. A significant decrease for AIV persistence models was recorded for sea water, after 12 days, at 35 degrees C. An effective inactivation has been shown when using commercially available products based on glutaraldehyde and penta potassium bis (peroxy mono sulphate) bis(sulphate), respectively. This rapid and safe method for decontamination, developed in this study, might be helpful in implementation of biosafety measures in laboratory and farms against AIV.

  7. Efficacy of a Levulinic Acid Plus Sodium Dodecyl Sulfate (SDS)-Based Sanitizer on Inactivation of Influenza A Virus on Eggshells.

    Science.gov (United States)

    Aydin, Ali; Cannon, Jennifer L; Zhao, Tong; Doyle, Michael P

    2013-10-17

    Influenza A virus poses a major public health concern and is associated with annual epidemics and occasional pandemics. Influenza A H3N2 viruses, which are an important cause of human influenza, can infect birds and mammals. Contaminated undercooked poultry products including eggs with avian influenza virus constitute a possible risk of transmission to humans. In this study, a novel levulinic acid plus sodium dodecyl sulfate (SDS) sanitizer was evaluated for eggshell decontamination. Influenza A H3N2 virus-inoculated chicken eggshells were treated with a 5 % levulinic acid plus 2 % SDS, 2 % levulinic acid plus 1 % SDS, and 0.5 % levulinic acid plus 0.5 % SDS liquid solution for 1 min. Log reductions of viable viruses were observed by plaque assay. The 5 % levulinic acid plus 2 % SDS sanitizer provided the greatest level of influenza A H3N2 virus inactivation (2.23 log PFU), and differences in virus inactivation were observed for the various levulinic acid plus SDS concentrations tested (P ≤ 0.05). To the best of our knowledge, this is the first study demonstrating influenza A H3N2 virus inactivation on eggshells using a novel levulinic acid plus SDS sanitizer. The sanitizer may be useful for reducing egg contamination and preventing the spread of avian influenza virus to humans.

  8. Cost-effectiveness analysis of quadrivalent seasonal influenza vaccines in England.

    Science.gov (United States)

    Thorrington, Dominic; van Leeuwen, Edwin; Ramsay, Mary; Pebody, Richard; Baguelin, Marc

    2017-09-08

    As part of the national seasonal influenza vaccination programme in England and Wales, children receive a quadrivalent vaccine offering protection against two influenza A strains and two influenza B strains. Healthy children receive a quadrivalent live attenuated influenza vaccine (QLAIV), whilst children with contraindications receive the quadrivalent inactivated influenza vaccine (QIIV). Individuals aged younger than 65 years in the clinical risk populations and elderly individuals aged 65+ years receive either a trivalent inactivated influenza vaccine (TIIV) offering protection from two A strains and one B strain or the QIIV at the choice of their general practitioner. The cost-effectiveness of quadrivalent vaccine programmes is an open question. The original analysis that supported the paediatric programme only considered a trivalent live attenuated vaccine (LAIV). The cost-effectiveness of the QIIV to other patients has not been established. We sought to estimate the cost-effectiveness of these programmes, establishing a maximum incremental total cost per dose of quadrivalent vaccines over trivalent vaccines. We used the same mathematical model as the analysis that recommended the introduction of the paediatric influenza vaccination programme. The incremental cost of the quadrivalent vaccine is the additional cost over that of the existing trivalent vaccine currently in use. Introducing quadrivalent vaccines can be cost-effective for all targeted groups. However, the cost-effectiveness of the programme is dependent on the choice of target cohort and the cost of the vaccines: the paediatric programme is cost-effective with an increased cost of £6.36 per dose, though an extension to clinical risk individuals younger than 65 years old and further to all elderly individuals means the maximum incremental cost is £1.84 and £0.20 per dose respectively. Quadrivalent influenza vaccines will bring substantial health benefits, as they are cost-effective in

  9. Simplifying influenza vaccination during pandemics : sublingual priming and intramuscular boosting of immune responses with heterologous whole inactivated influenza vaccine

    NARCIS (Netherlands)

    Murugappan, Senthil; Patil, Harshad P; Frijlink, Henderik W; Huckriede, Anke; Hinrichs, Wouter L J

    2014-01-01

    The best approach to control the spread of influenza virus during a pandemic is vaccination. Yet, an appropriate vaccine is not available early in the pandemic since vaccine production is time consuming. For influenza strains with a high pandemic potential like H5N1, stockpiling of vaccines has been

  10. Comparison of influenza vaccine effectiveness in preventing outpatient and inpatient influenza cases in older adults, northern Spain, 2010/11 to 2015/16.

    Science.gov (United States)

    Castilla, Jesús; Martínez-Baz, Iván; Navascués, Ana; Casado, Itziar; Aguinaga, Aitziber; Díaz-González, Jorge; Delfrade, Josu; Guevara, Marcela; Ezpeleta, Carmen

    2018-01-01

    IntroductionWe compared trivalent inactivated influenza vaccine effectiveness (VE) in preventing outpatient and inpatient influenza cases in Navarre, Spain. Methods: During seasons 2010/11 to 2015/16, community-dwelling patients with influenza-like illness aged 50 years or older were tested for influenza when attended by sentinel general practitioners or admitted to hospitals. The test-negative design was used to estimate and compare the VE by healthcare setting. Results: We compared 1,242 laboratory-confirmed influenza cases (557 outpatient and 685 inpatient cases) and 1,641 test-negative controls. Influenza VE was 34% (95% confidence interval (CI): 6 to 54) in outpatients and 32% (95% CI: 15 to 45) in inpatients. VE in outpatients and inpatients was, respectively, 41% (95% CI: -1 to 65) and 36% (95% CI: 12 to 53) against A(H1N1)pdm09, 5% (95% CI: -58 to 43) and 22% (95% CI: -9 to 44) against A(H3N2), and 49% (95% CI, 6 to 73) and 37% (95% CI: 2 to 59) against influenza B. Trivalent inactivated influenza vaccine was not associated with a different probability of hospitalisation among influenza cases, apart from a 54% (95% CI: 10 to 76) reduction in hospitalisation of influenza A(H3N2) cases. Conclusions: On average, influenza VE was moderate and similar in preventing outpatient and inpatient influenza cases over six influenza seasons in patients above 50 years of age. In some instances of low VE, vaccination may still reduce the risk of hospitalisation in older adults with vaccine failure.

  11. Accumulation and Inactivation of Avian Influenza Virus by the Filter-Feeding Invertebrate Daphnia magna

    Science.gov (United States)

    Borchardt, Mark A.; Spencer, Susan K.

    2013-01-01

    The principal mode of avian influenza A virus (AIV) transmission among wild birds is thought to occur via an indirect fecal-oral route, whereby individuals are exposed to virus from the environment through contact with virus-contaminated water. AIV can remain viable for an extended time in water; however, little is known regarding the influence of the biotic community (i.e., aquatic invertebrates) on virus persistence and infectivity in aquatic environments. We conducted laboratory experiments to investigate the ability of an aquatic filter-feeding invertebrate, Daphnia magna, to accumulate virus from AIV-dosed water under the hypothesis that they represent a potential vector of AIV to waterfowl hosts. We placed live daphnids in test tubes dosed with low-pathogenicity AIV (H3N8 subtype isolated from a wild duck) and sampled Daphnia tissue and the surrounding water using reverse transcription-quantitative PCR (RT-qPCR) at 3- to 120-min intervals for up to 960 min following dosing. Concentrations of viral RNA averaged 3 times higher in Daphnia tissue than the surrounding water shortly after viral exposure, but concentrations decreased exponentially through time for both. Extracts from Daphnia tissue were negative for AIV by cell culture, whereas AIV remained viable in water without Daphnia present. Our results suggest daphnids can accumulate AIV RNA and effectively remove virus particles from water. Although concentrations of viral RNA were consistently higher in Daphnia tissue than the water, additional research is needed on the time scale of AIV inactivation after Daphnia ingestion to fully elucidate Daphnia's role as a potential vector of AIV infection to aquatic birds. PMID:24038705

  12. Topical imiquimod before intradermal trivalent influenza vaccine for protection against heterologous non-vaccine and antigenically drifted viruses: a single-centre, double-blind, randomised, controlled phase 2b/3 trial.

    Science.gov (United States)

    Hung, Ivan Fan-Ngai; Zhang, Anna Jinxia; To, Kelvin Kai-Wang; Chan, Jasper Fuk-Woo; Li, Patrick; Wong, Tin-Lun; Zhang, Ricky; Chan, Tuen-Ching; Chan, Brian Chun-Yuan; Wai, Harrison Ho; Chan, Lok-Wun; Fong, Hugo Pak-Yiu; Hui, Raymond Kar-Ching; Kong, Ka-Lun; Leung, Arthur Chun-Fung; Ngan, Abe Ho-Ting; Tsang, Louise Wing-Ki; Yeung, Alex Pat-Chung; Yiu, Geo Chi-Ngo; Yung, Wing; Lau, Johnson Y-N; Chen, Honglin; Chan, Kwok-Hung; Yuen, Kwok-Yung

    2016-02-01

    Pretreatment with topical imiquimod, a synthetic agonist of toll-like receptor 7, significantly improved the immunogenicity of influenza vaccination in elderly people. We aimed to clarify its effect in a younger age group. In this double-blind, randomised controlled trial, we enrolled healthy volunteers aged 18-30 years in early 2014 to receive the 2013-14 northern-hemisphere winter trivalent influenza vaccine at the Queen Mary Hospital, (Hong Kong, China). Eligible participants were randomly assigned (1:1:1:1) to one of the four vaccination groups: the study group, topical imiquimod-cream followed by intradermal trivalent influenza vaccine (INF-Q-ID), or one of three control groups, topical aqueous-cream control followed by intradermal trivalent influenza vaccine (INF-C-ID), topical aqueous-cream control followed by intramuscular trivalent influenza vaccine (INF-C-IM), and topical imiquimod-cream followed by intradermal normal-saline injection (SAL-Q-ID). Randomisation was by computer-generated lists in blocks of four. The type of topical treatment was masked from volunteers and investigators, although not from the study nurse. Serum haemagglutination-inhibition and microneutralisation-antibody titres were assayed. The primary outcome was seroconversion at day 7 after treatment for three vaccine strains of influenza (A/California/07/2009 H1N1-like virus [A/California/H1N1], A/Victoria/361/2011 H3N2-like virus [A/Victoria/H3N2], and B/Massachusetts/2/2012-like virus [B/Yamagata lineage]) and four non-vaccine strains (A/HK/485197/14 [H3N2 Switzerland-like lineage], prototype A/WSN/1933 [H1N1], A/HK/408027/09 [prepandemic seasonal H1N1], and B/HK/418078/11 [Victoria lineage]). Analysis was done on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, number NCT02103023. We enrolled 160 healthy volunteers between March 1 and May 31, 2014, and 40 participants were randomly assigned to each study group. For the A/California/H1N1 strain

  13. Clinical and immune responses to inactivated influenza A(H1N1)pdm09 vaccine in children.

    Science.gov (United States)

    Kotloff, Karen L; Halasa, Natasha B; Harrison, Christopher J; Englund, Janet A; Walter, Emmanuel B; King, James C; Creech, C Buddy; Healy, Sara A; Dolor, Rowena J; Stephens, Ina; Edwards, Kathryn M; Noah, Diana L; Hill, Heather; Wolff, Mark

    2014-08-01

    As the influenza A H1N1 pandemic emerged in 2009, children were found to experience high morbidity and mortality and were prioritized for vaccination. This multicenter, randomized, double-blind, age-stratified trial assessed the safety and immunogenicity of inactivated influenza A(H1N1)pdm09 vaccine in healthy children aged 6 months to 17 years. Children received 2 doses of approximately 15 or 30 µg hemagglutin antigen 21 days apart. Reactogenicity was assessed for 8 days after each dose, adverse events through day 42, and serious adverse events or new-onset chronic illnesses through day 201. Serum hemagglutination inhibition titers were measured on days 0 (prevaccination), 8, 21, 29 and 42. A total of 583 children received the first dose and 571 received the second dose of vaccine. Vaccinations were generally well-tolerated and no related serious adverse events were observed. The 15 µg dosage elicited a seroprotective hemagglutination inhibition (≥ 1:40) in 20%, 47% and 93% of children in the 6-35 month, 3-9 year and 10-17 year age strata 21 days after dose 1 and in 78%, 82% and 98% of children 21 days after dose 2, respectively. The 30 µg vaccine dosage induced similar responses. The inactivated influenza A(H1N1)pdm09 vaccine exhibited a favorable safety profile at both dosage levels. While a single 15 or 30 µg dose induced seroprotective antibody responses in most children 10-17 years of age, younger children required 2 doses, even when receiving dosages 4- to 6-fold higher than recommended. Well-tolerated vaccines are needed that induce immunity after a single dose for use in young children during influenza pandemics.

  14. Neutralizing Antibody Responses to Antigenically Drifted Influenza A(H3N2) Viruses among Children and Adolescents following 2014-2015 Inactivated and Live Attenuated Influenza Vaccination

    Science.gov (United States)

    Martin, Judith M.; Gross, F. Liaini; Jefferson, Stacie; Cole, Kelly Stefano; Archibald, Crystal Ann; Nowalk, Mary Patricia; Susick, Michael; Moehling, Krissy; Spencer, Sarah; Chung, Jessie R.; Flannery, Brendan; Zimmerman, Richard K.

    2016-01-01

    Human influenza A(H3N2) viruses that predominated during the moderately severe 2014-2015 influenza season differed antigenically from the vaccine component, resulting in reduced vaccine effectiveness (VE). To examine antibody responses to 2014-2015 inactivated influenza vaccine (IIV) and live-attenuated influenza vaccine (LAIV) among children and adolescents, we collected sera before and after vaccination from 150 children aged 3 to 17 years enrolled at health care facilities. Hemagglutination inhibition (HI) assays were used to assess the antibody responses to vaccine strains. We evaluated cross-reactive antibody responses against two representative A(H3N2) viruses that had antigenically drifted from the A(H3N2) vaccine component using microneutralization (MN) assays. Postvaccination antibody titers to drifted A(H3N2) viruses were higher following receipt of IIV (MN geometric mean titers [GMTs], 63 to 68; 38 to 45% achieved seroconversion) versus LAIV (MN GMT, 22; only 3 to 5% achieved seroconversion). In 9- to 17-year-olds, the highest MN titers were observed among IIV-vaccinated individuals who had received LAIV in the previous season. Among all IIV recipients aged 3 to 17 years, the strongest predictor of antibody responses to the drifted viruses was the prevaccination titers to the vaccine strain. The results of our study suggest that in an antigenically drifted influenza season, vaccination still induced cross-reactive antibody responses to drifted circulating A(H3N2) viruses, although higher antibody titers may be required for protection. Antibody responses to drifted A(H3N2) viruses following vaccination were influenced by multiple factors, including vaccine type and preexisting immunity from prior exposure. PMID:27558294

  15. Randomized evaluation of live attenuated vs. inactivated influenza vaccines in schools (RELATIVES) pilot study: a cluster randomized trial.

    Science.gov (United States)

    Kwong, Jeffrey C; Pereira, Jennifer A; Quach, Susan; Pellizzari, Rosana; Dusome, Edwina; Russell, Margaret L; Hamid, Jemila S; Feinberg, Yael; Winter, Anne-Luise; Gubbay, Jonathan B; Sirtonski, Brittany; Moher, Deanna; Sider, Doug; Finkelstein, Michael; Loeb, Mark

    2015-01-15

    School-based influenza immunization can effectively address accessibility barriers, but injected inactivated influenza vaccines (IIV) may not be acceptable to some children and parents in school settings. To better understand the feasibility of offering intranasal live attenuated influenza vaccines (LAIV) through schools, we assessed uptake, stakeholder acceptability, and cost of school-based delivery of LAIV compared to IIV. We piloted an open-label cluster randomized trial involving 10 elementary schools in Peterborough, Ontario during the 2013-2014 influenza vaccination campaign. Schools were randomized to having students receive IIV or LAIV at publicly-funded school-based clinics organized by the local public health department. We measured the percentage of students vaccinated with at least one dose of influenza vaccine at school. Stakeholder acceptability was evaluated through a questionnaire of parents and interviews of public health department personnel and school principals. We compared the costs per dose of vaccine administered, including staff time and costs of vaccines and supplies. Single-dose influenza vaccine uptake was higher for the five schools offering LAIV than for the five offering IIV (19.3% vs. 12.2%, p=0.02). Interviews with nine school principals and five public health department personnel suggested that the clinics ran smoothly with little disruption to school routines, and that LAIV was associated with increased efficiency and calmer children. All interviewees cited unfamiliarity with LAIV and the study recruitment package length as potential reasons for low uptake. The cost per vaccine dose administered was $38.67 for IIV and $43.50 for LAIV. Use of LAIV in school-based clinics was associated with increased vaccine uptake and the perception among immunizing staff of reduced child anxiety, but also slightly higher vaccine administration costs, compared to IIV. However, uptake was low for both groups. More effective strategies to promote

  16. Whole inactivated equine influenza vaccine: Efficacy against a representative clade 2 equine influenza virus, IFNgamma synthesis and duration of humoral immunity.

    Science.gov (United States)

    Paillot, R; Prowse, L; Montesso, F; Huang, C M; Barnes, H; Escala, J

    2013-03-23

    Equine influenza (EI) is a serious respiratory disease of horses induced by the equine influenza virus (EIV). Surveillance, quarantine procedures and vaccination are widely used to prevent or to contain the disease. This study aimed to further characterise the immune response induced by a non-updated inactivated EI and tetanus vaccine, including protection against a representative EIV isolate of the Florida clade 2 sublineage. Seven ponies were vaccinated twice with Duvaxyn IE-T Plus at an interval of four weeks. Five ponies remained unvaccinated. All ponies were experimentally infected with the EIV strain A/eq/Richmond/1/07 two weeks after the second vaccination. Clinical signs of disease were recorded and virus shedding was measured after experimental infection. Antibody response and EIV-specific IFNgamma synthesis, a marker of cell-mediated immunity, were measured at different time points of the study. Vaccination resulted in significant protection against clinical signs of disease induced by A/eq/Richmond/1/07 and reduced virus shedding when challenged at the peak of immunity. Antigenic drift has been shown to reduce protection against EIV infection. Inclusion of a more recent and representative EIV vaccine strain, as recommended by the OIE expert surveillance panel on equine influenza vaccine, may maximise field protection. In addition, significant levels of EIV-specific IFNgamma synthesis by peripheral blood lymphocytes were detected in immunised ponies, which provided a first evidence of CMI stimulation after vaccination with a whole inactivated EIV. Duration of humoral response was also retrospectively investigated in 14 horses vaccinated under field condition and following the appropriate immunisation schedule, up to 599 days after first immunisation. This study revealed that most immunised horses maintained significant levels of cross-reactive SRH antibody for a prolonged period of time, but individual monitoring may be beneficial to identify poor vaccine

  17. Induction of heterosubtypic cross-protection against influenza by a whole inactivated virus vaccine: the role of viral membrane fusion activity.

    Directory of Open Access Journals (Sweden)

    Natalija Budimir

    Full Text Available BACKGROUND: The inability of seasonal influenza vaccines to effectively protect against infection with antigenically drifted viruses or newly emerging pandemic viruses underlines the need for development of cross-reactive influenza vaccines that induce immunity against a variety of virus subtypes. Therefore, potential cross-protective vaccines, e.g., whole inactivated virus (WIV vaccine, that can target conserved internal antigens such as the nucleoprotein (NP and/or matrix protein (M1 need to be explored. METHODOLOGY/PRINCIPAL FINDINGS: In the current study we show that a WIV vaccine, through induction of cross-protective cytotoxic T lymphocytes (CTLs, protects mice from heterosubtypic infection. This protection was abrogated after depletion of CD8+ cells in vaccinated mice, indicating that CTLs were the primary mediators of protection. Previously, we have shown that different procedures used for virus inactivation influence optimal activation of CTLs by WIV, most likely by affecting the membrane fusion properties of the virus. Specifically, inactivation with formalin (FA severely compromises fusion activity of the virus, while inactivation with β-propiolactone (BPL preserves fusion activity. Here, we demonstrate that vaccination of mice with BPL-inactivated H5N1 WIV vaccine induces solid protection from lethal heterosubtypic H1N1 challenge. By contrast, vaccination with FA-inactivated WIV, while preventing death after lethal challenge, failed to protect against development of disease and severe body weight loss. Vaccination with BPL-inactivated WIV, compared to FA-inactivated WIV, induced higher levels of specific CD8+ T cells in blood, spleen and lungs, and a higher production of granzyme B in the lungs upon H1N1 virus challenge. CONCLUSION/SIGNIFICANCE: The results underline the potential use of WIV as a cross-protective influenza vaccine candidate. However, careful choice of the virus inactivation procedure is important to retain membrane

  18. Induction of heterosubtypic cross-protection against influenza by a whole inactivated virus vaccine: the role of viral membrane fusion activity.

    Science.gov (United States)

    Budimir, Natalija; Huckriede, Anke; Meijerhof, Tjarko; Boon, Louis; Gostick, Emma; Price, David A; Wilschut, Jan; de Haan, Aalzen

    2012-01-01

    The inability of seasonal influenza vaccines to effectively protect against infection with antigenically drifted viruses or newly emerging pandemic viruses underlines the need for development of cross-reactive influenza vaccines that induce immunity against a variety of virus subtypes. Therefore, potential cross-protective vaccines, e.g., whole inactivated virus (WIV) vaccine, that can target conserved internal antigens such as the nucleoprotein (NP) and/or matrix protein (M1) need to be explored. In the current study we show that a WIV vaccine, through induction of cross-protective cytotoxic T lymphocytes (CTLs), protects mice from heterosubtypic infection. This protection was abrogated after depletion of CD8+ cells in vaccinated mice, indicating that CTLs were the primary mediators of protection. Previously, we have shown that different procedures used for virus inactivation influence optimal activation of CTLs by WIV, most likely by affecting the membrane fusion properties of the virus. Specifically, inactivation with formalin (FA) severely compromises fusion activity of the virus, while inactivation with β-propiolactone (BPL) preserves fusion activity. Here, we demonstrate that vaccination of mice with BPL-inactivated H5N1 WIV vaccine induces solid protection from lethal heterosubtypic H1N1 challenge. By contrast, vaccination with FA-inactivated WIV, while preventing death after lethal challenge, failed to protect against development of disease and severe body weight loss. Vaccination with BPL-inactivated WIV, compared to FA-inactivated WIV, induced higher levels of specific CD8+ T cells in blood, spleen and lungs, and a higher production of granzyme B in the lungs upon H1N1 virus challenge. The results underline the potential use of WIV as a cross-protective influenza vaccine candidate. However, careful choice of the virus inactivation procedure is important to retain membrane fusion activity and full immunogenicity of the vaccine.

  19. Effects of Repeated Annual Inactivated Influenza Vaccination among Healthcare Personnel on Serum Hemagglutinin Inhibition Antibody Response to A/Perth/16/2009 (H3N2)-like virus during 2010–11

    Science.gov (United States)

    Thompson, Mark G.; Naleway, Allison; Fry, Alicia M.; Ball, Sarah; Spencer, Sarah M.; Reynolds, Sue; Bozeman, Sam; Levine, Min; Katz, Jacqueline M.; Gaglani, Manjusha

    2016-01-01

    Background Recently, lower estimates of influenza vaccine effectiveness (VE) against A(H3N2) virus illness among those vaccinated during the previous season or multiple seasons have been reported; however, it is unclear whether these effects are due to differences in immunogenicity. Methods We performed hemagglutination inhibition antibody (HI) assays on serum collected at preseason, ∼30 days post-vaccination, and postseason from a prospective cohort of healthcare personnel (HCP). Eligible participants had medical and vaccination records for at least four years (since July, 2006), including 578 HCP who received 2010–11 trivalent inactivated influenza vaccine [IIV3, containing A/Perth/16/2009-like A(H3N2)] and 209 HCP who declined vaccination. Estimates of the percentage with high titers (≥40 and > 100) and geometric mean fold change ratios (GMRs) to A/Perth/16/2009-like virus by number of prior vaccinations were adjusted for age, sex, race, education, household size, hospital care responsibilities, and study site. Results Post-vaccination GMRs were inversely associated with the number of prior vaccinations, increasing from 2.3 among those with 4 prior vaccinations to 6.2 among HCP with zero prior vaccinations (F[4,567] = 9.97, p vaccination achieved titers >100 compared to only 11% of HCP with 4 prior vaccinations (adjusted odds ratio = 6.8, 95% CI = 3.1 – 15.3). Conclusion Our findings point to an exposure-response association between repeated IIV3 vaccination and HI for A(H3N2) and are consistent with recent VE observations. Ultimately, better vaccines and vaccine strategies may be needed in order to optimize immunogenicity and VE for HCP and other repeated vaccinees. PMID:26813801

  20. Effects of Repeated Annual Inactivated Influenza Vaccination among Healthcare Personnel on Serum Hemagglutinin Inhibition Antibody Response to A/Perth/16/2009 (H3N2)-like virus during 2010-11.

    Science.gov (United States)

    Thompson, Mark G; Naleway, Allison; Fry, Alicia M; Ball, Sarah; Spencer, Sarah M; Reynolds, Sue; Bozeman, Sam; Levine, Min; Katz, Jacqueline M; Gaglani, Manjusha

    2016-02-10

    Recently, lower estimates of influenza vaccine effectiveness (VE) against A(H3N2) virus illness among those vaccinated during the previous season or multiple seasons have been reported; however, it is unclear whether these effects are due to differences in immunogenicity. We performed hemagglutination inhibition antibody (HI) assays on serum collected at preseason, ∼ 30 days post-vaccination, and postseason from a prospective cohort of healthcare personnel (HCP). Eligible participants had medical and vaccination records for at least four years (since July, 2006), including 578 HCP who received 2010-11 trivalent inactivated influenza vaccine [IIV3, containing A/Perth/16/2009-like A(H3N2)] and 209 HCP who declined vaccination. Estimates of the percentage with high titers (≥ 40 and>100) and geometric mean fold change ratios (GMRs) to A/Perth/16/2009-like virus by number of prior vaccinations were adjusted for age, sex, race, education, household size, hospital care responsibilities, and study site. Post-vaccination GMRs were inversely associated with the number of prior vaccinations, increasing from 2.3 among those with 4 prior vaccinations to 6.2 among HCP with zero prior vaccinations (F[4,567]=9.97, pvaccination achieved titers >100 compared to only 11% of HCP with 4 prior vaccinations (adjusted odds ratio=6.8, 95% CI=3.1 - 15.3). Our findings point to an exposure-response association between repeated IIV3 vaccination and HI for A(H3N2) and are consistent with recent VE observations. Ultimately, better vaccines and vaccine strategies may be needed in order to optimize immunogenicity and VE for HCP and other repeated vaccinees. Published by Elsevier Ltd.

  1. Mucosal Immunity and Protective Efficacy of Intranasal Inactivated Influenza Vaccine Is Improved by Chitosan Nanoparticle Delivery in Pigs

    Directory of Open Access Journals (Sweden)

    Santosh Dhakal

    2018-05-01

    Full Text Available Annually, swine influenza A virus (SwIAV causes severe economic loss to swine industry. Currently used inactivated SwIAV vaccines administered by intramuscular injection provide homologous protection, but limited heterologous protection against constantly evolving field viruses, attributable to the induction of inadequate levels of mucosal IgA and cellular immune responses in the respiratory tract. A novel vaccine delivery platform using mucoadhesive chitosan nanoparticles (CNPs administered through intranasal (IN route has the potential to elicit strong mucosal and systemic immune responses in pigs. In this study, we evaluated the immune responses and cross-protective efficacy of IN chitosan encapsulated inactivated SwIAV vaccine in pigs. Killed SwIAV H1N2 (δ-lineage antigens (KAg were encapsulated in chitosan polymer-based nanoparticles (CNPs-KAg. The candidate vaccine was administered twice IN as mist to nursery pigs. Vaccinates and controls were then challenged with a zoonotic and virulent heterologous SwIAV H1N1 (γ-lineage. Pigs vaccinated with CNPs-KAg exhibited an enhanced IgG serum antibody and mucosal secretory IgA antibody responses in nasal swabs, bronchoalveolar lavage (BAL fluids, and lung lysates that were reactive against homologous (H1N2, heterologous (H1N1, and heterosubtypic (H3N2 influenza A virus strains. Prior to challenge, an increased frequency of cytotoxic T lymphocytes, antigen-specific lymphocyte proliferation, and recall IFN-γ secretion by restimulated peripheral blood mononuclear cells in CNPs-KAg compared to control KAg vaccinates were observed. In CNPs-KAg vaccinated pigs challenged with heterologous virus reduced severity of macroscopic and microscopic influenza-associated pulmonary lesions were observed. Importantly, the infectious SwIAV titers in nasal swabs [days post-challenge (DPC 4] and BAL fluid (DPC 6 were significantly (p < 0.05 reduced in CNPs-KAg vaccinates but not in KAg vaccinates when compared

  2. Immunogenicity and efficacy of fowlpox-vectored and inactivated avian influenza vaccines alone or in a prime-boost schedule in chickens with maternal antibodies

    Science.gov (United States)

    Inactivated and fowlpox (FP)-vectored vaccines have been used to control avian influenza (AI) in poultry. In endemic countries, breeder flocks are vaccinated and therefore, maternally-derived antibodies (MDA) are transferred to their progeny. Results of several immunogenicity and efficacy studies ...

  3. Adenovirus vectored vaccines against influenza a virus do not result in vaccine associated enhanced respiratory disease following heterologous challenge in contrast to whole inactivated virus vaccine

    Science.gov (United States)

    Heterologous influenza A virus (IAV) challenge following vaccination with an intramuscular (IM) whole inactivated vaccine (WIV) can result in vaccine-associated enhanced respiratory disease (VAERD). The objective of this study was to use an adenovirus (Ad5) vector vaccine platform that expressed IAV...

  4. Efficacy, safety, and immunogenicity of a Vero-cell-culture-derived trivalent influenza vaccine: a multicentre, double-blind, randomised, placebo-controlled trial.

    Science.gov (United States)

    Barrett, P Noel; Berezuk, Gregory; Fritsch, Sandor; Aichinger, Gerald; Hart, Mary Kate; El-Amin, Wael; Kistner, Otfried; Ehrlich, Hartmut J

    2011-02-26

    The use of cell-culture technologies for the manufacture of influenza vaccines might contribute to improved strain selection and robust vaccine supplies. We investigated the safety, immunogenicity, and protective efficacy of a Vero-cell-culture-derived influenza vaccine, and assessed the correlation between vaccine efficacy and haemagglutination inhibition antibody titre. In a double-blind, placebo-controlled, phase 3 trial undertaken in 36 centres in the USA, healthy adults (aged 18-49 years) were randomly assigned in a 1:1 ratio to one injection of either placebo or Vero-cell-culture-derived influenza vaccine during the 2008-09 season. Randomisation was done in blocks by use of the random number generator algorithm, and participants were allocated by use of a centralised telephone system. The primary objective was the efficacy of the vaccine in preventing cell-culture-confirmed influenza infection with viruses that were antigenically matched to one of the vaccine strains. Analysis was by intention to treat. The study is registered with ClinicalTrials.gov, number NCT00566345. 7250 participants were randomly assigned to vaccine (n=3626) and placebo (n=3624). 7236 were analysed for the primary outcome (n=3619 and n=3617, respectively). Overall protective efficacy for antigenically matched influenza infection was 78·5% (95% CI 60·8-88·2). The vaccine was well tolerated with no treatment-related serious adverse events. Adverse events were mainly mild and transient. An HI titre of at least 1:15 provided a reliable correlate of cell-culture-derived influenza vaccine-induced protection; no additional benefit was noted with titres greater than 1:30. The data indicate that existing correlates of protection afforded with egg-derived seasonal influenza vaccines also apply to this vaccine. Federal (US Government) funds from the Office for Preparedness and Response, Biomedical Advanced Research and Development Authority, under contract to DynPort Vaccine Company. Copyright

  5. Enhanced pulmonary immunization with aerosolized inactivated influenza vaccine containing delta inulin adjuvant

    NARCIS (Netherlands)

    Murugappan, Senthil; Frijlink, Henderik W.; Petrovsky, Nikolai; Hinrichs, Wouter L. J.

    2015-01-01

    Vaccination is the primary intervention to contain influenza virus spread during seasonal and pandemic outbreaks. Pulmonary vaccination is gaining increasing attention for its ability to induce both local mucosal and systemic immune responses without the need for invasive injections. However,

  6. Protective efficacy of recombinant and inactivated H5 avian influenza vaccines against challenge from the 2014 intercontinental H5 highly pathogenic avian influenza viruses (H5N8 and H5N2)

    Science.gov (United States)

    Protective immunity against highly pathogenic avian influenza (HPAI) largely depends on the development of an antibody response against a specific subtype of challenge virus. Historically, the use of antigenically closely matched isolates has proven efficacious when used as inactivated vaccines. M...

  7. Biodegradable nanoparticle delivery of inactivated swine influenza virus vaccine provides heterologous cell-mediated immune response in pigs.

    Science.gov (United States)

    Dhakal, Santosh; Hiremath, Jagadish; Bondra, Kathryn; Lakshmanappa, Yashavanth S; Shyu, Duan-Liang; Ouyang, Kang; Kang, Kyung-Il; Binjawadagi, Basavaraj; Goodman, Jonathan; Tabynov, Kairat; Krakowka, Steven; Narasimhan, Balaji; Lee, Chang Won; Renukaradhya, Gourapura J

    2017-02-10

    Swine influenza virus (SwIV) is one of the important zoonotic pathogens. Current flu vaccines have failed to provide cross-protection against evolving viruses in the field. Poly(lactic-co-glycolic acid) (PLGA) is a biodegradable FDA approved polymer and widely used in drug and vaccine delivery. In this study, inactivated SwIV H1N2 antigens (KAg) encapsulated in PLGA nanoparticles (PLGA-KAg) were prepared, which were spherical in shape with 200 to 300nm diameter, and induced maturation of antigen presenting cells in vitro. Pigs vaccinated twice with PLGA-KAg via intranasal route showed increased antigen specific lymphocyte proliferation and enhanced the frequency of T-helper/memory and cytotoxic T cells (CTLs) in peripheral blood mononuclear cells (PBMCs). In PLGA-KAg vaccinated and heterologous SwIV H1N1 challenged pigs, clinical flu symptoms were absent, while the control pigs had fever for four days. Grossly and microscopically, reduced lung pathology and viral antigenic mass in the lung sections with clearance of infectious challenge virus in most of the PLGA-KAg vaccinated pig lung airways were observed. Immunologically, PLGA-KAg vaccine irrespective of not significantly boosting the mucosal antibody response, it augmented the frequency of IFN-γ secreting total T cells, T-helper and CTLs against both H1N2 and H1N1 SwIV. In summary, inactivated influenza virus delivered through PLGA-NPs reduced the clinical disease and induced cross-protective cell-mediated immune response in a pig model. Our data confirmed the utility of a pig model for intranasal particulate flu vaccine delivery platform to control flu in humans. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Live attenuated H7N7 influenza vaccine primes for a vigorous antibody response to inactivated H7N7 influenza vaccine.

    Science.gov (United States)

    Babu, Tara M; Levine, Min; Fitzgerald, Theresa; Luke, Catherine; Sangster, Mark Y; Jin, Hong; Topham, David; Katz, Jacqueline; Treanor, John; Subbarao, Kanta

    2014-11-28

    H7 influenza viruses have emerged as potential pandemic threat. We evaluated the safety and immunogenicity of two candidate H7 pandemic live attenuated influenza vaccines (pLAIV) and their ability to prime for responses to an unadjuvanted H7 pandemic inactivated influenza vaccine (pIIV). Healthy seronegative adults received two doses of A/Netherlands/219/03 (H7N7) or one dose of A/chicken/British Columbia/CN-6/04 (H7N3) pLAIV all given as 10(7.5) 50% tissue culture infective doses (TCID50) intranasally. A subset of subjects received one 45 μg dose of H7N7 pIIV containing the A/Mallard/Netherlands/12/2000 HA intramuscularly 18-24 months after pLAIV. Viral shedding was assessed by culture and real-time polymerase chain reaction (rRT-PCR), B cell responses following pLAIV were evaluated by ELISPOT and flow cytometry. Serum antibody was assessed by hemagglutination-inhibition (HAI), microneutralization (MN) and ELISA assays after each vaccine. Serum HAI or MN responses were not detected in any subject following one or two doses of either H7 pLAIV, although some subjects had detectable H7 specific B cells after vaccination. However, 10/13 subjects primed with two doses of H7N7 pLAIV responded to a subsequent dose of the homologous H7N7 pIIV with high titer HAI and MN antibody that cross-reacted with both North American and Eurasian lineage H7 viruses, including H7N9. In contrast, naïve subjects and recipients of a single dose of the mismatched H7N3 pLAIV did not develop HAI or MN antibody after pIIV. While pLAIVs did not elicit detectable serum MN or HAI antibody, strain-specific pLAIV priming established long term immune memory that was cross-reactive with other H7 influenza strains. Understanding the mechanisms underlying priming by pLAIV may aid in pandemic vaccine development. Copyright © 2014. Published by Elsevier Ltd.

  9. Production of inactivated influenza H5N1 vaccines from MDCK cells in serum-free medium.

    Directory of Open Access Journals (Sweden)

    Alan Yung-Chih Hu

    Full Text Available BACKGROUND: Highly pathogenic influenza viruses pose a constant threat which could lead to a global pandemic. Vaccination remains the principal measure to reduce morbidity and mortality from such pandemics. The availability and surging demand for pandemic vaccines needs to be addressed in the preparedness plans. This study presents an improved high-yield manufacturing process for the inactivated influenza H5N1 vaccines using Madin-Darby canine kidney (MDCK cells grown in a serum-free (SF medium microcarrier cell culture system. PRINCIPAL FINDING: The current study has evaluated the performance of cell adaptation switched from serum-containing (SC medium to several commercial SF media. The selected SF medium was further evaluated in various bioreactor culture systems for process scale-up evaluation. No significant difference was found in the cell growth in different sizes of bioreactors studied. In the 7.5 L bioreactor runs, the cell concentration reached to 2.3 × 10(6 cells/mL after 5 days. The maximum virus titers of 1024 Hemagglutinin (HA units/50 µL and 7.1 ± 0.3 × 10(8 pfu/mL were obtained after 3 days infection. The concentration of HA antigen as determined by SRID was found to be 14.1 µg/mL which was higher than those obtained from the SC medium. A mouse immunogenicity study showed that the formalin-inactivated purified SF vaccine candidate formulated with alum adjuvant could induce protective level of virus neutralization titers similar to those obtained from the SC medium. In addition, the H5N1 viruses produced from either SC or SF media showed the same antigenic reactivity with the NIBRG14 standard antisera. CONCLUSIONS: The advantages of this SF cell-based manufacturing process could reduce the animal serum contamination, the cost and lot-to-lot variation of SC medium production. This study provides useful information to manufacturers that are planning to use SF medium for cell-based influenza vaccine production.

  10. Influenza virus inactivation for studies of antigenicity and phenotypic neuraminidase inhibitor resistance profiling

    NARCIS (Netherlands)

    M. Jonges (Marcel); W.M. Liu; E. van der Vries (Erhard); R. Jacobi (Ronald); I. Pronk (Inge); C. Boog (Claire); M.P.G. Koopmans D.V.M. (Marion); A. Meijer (Adam); E. Soethout (Ernst)

    2010-01-01

    textabstractIntroduction of a new influenza virus in humans urges quick analysis of its virological and immunological characteristics to determine the impact on public health and to develop protective measures for the human population. At present, however, the necessity of executing pandemic

  11. Accumulation and inactivation of avian influenza virus by the filter feeding invertebrate daphnia magna

    Science.gov (United States)

    The principle mode of avian influenza A virus (AIV) transmission among wild birds is thought to occur via an indirect fecal-oral route, whereby individuals contract the virus from the environment through contact with virus-contaminated water. AIV can remain viable for periods of months to years in w...

  12. Effective influenza vaccines for children

    Science.gov (United States)

    Banzhoff, Angelika; Stoddard, Jeffrey J.

    2012-01-01

    Seasonal influenza causes clinical illness and hospitalization in all age groups; however, conventional inactivated vaccines have only limited efficacy in young children. MF59®, an oil-in-water emulsion adjuvant, has been used since the 1990s to enhance the immunogenicity of influenza vaccines in the elderly, a population with waning immune function due to immunosenescence.   Clinical trials now provide information to support a favorable immunogenicity and safety profile of MF59-adjuvanted influenza vaccine in young children. Published data indicate that Fluad®, a trivalent seasonal influenza vaccine with MF59, was immunogenic and well tolerated in young children, with a benefit/risk ratio that supports routine clinical use. A recent clinical trial also shows that Fluad provides high efficacy against PCR-confirmed influenza. Based on the results of clinical studies in children, the use of MF59-adjuvanted vaccine offers the potential to enhance efficacy and make vaccination a viable prevention and control strategy in this population. PMID:22327501

  13. Calcium phosphate nanoparticle (CaPNP) for dose-sparing of inactivated whole virus pandemic influenza A (H1N1) 2009 vaccine in mice.

    Science.gov (United States)

    Morçӧl, Tülin; Hurst, Brett L; Tarbet, E Bart

    2017-08-16

    The emergence of pandemic influenza strains, particularly the reemergence of the swine-derived influenza A (H1N1) in 2009, is reaffirmation that influenza viruses are very adaptable and influenza remains as a significant global public health treat. As recommended by the World Health Organization (WHO), the use of adjuvants is an attractive approach to improve vaccine efficacy and allow dose-sparing during an influenza emergency. In this study, we utilized CaPtivate Pharmaceutical's proprietary calcium phosphate nanoparticles (CaPNP) vaccine adjuvant and delivery platform to formulate an inactivated whole virus influenza A/CA/04/2009 (H1N1pdm) vaccine as a potential dose-sparing strategy. We evaluated the relative immunogenicity and the efficacy of the formulation in BALB/c mice following single intramuscularly administration of three different doses (0.3, 1, or 3µg based on HA content) of the vaccine in comparison to non-adjuvanted or alum-adjuvant vaccines. We showed that, addition of CaPNP in vaccine elicited significantly higher hemagglutination inhibition (HAI), virus neutralization (VN), and IgG antibody titers, at all dose levels, relative to the non-adjuvanted vaccine. In addition, the vaccine containing CaPNP provided equal protection with 1/3rd of the antigen dose as compared to the non-adjuvanted or alum-adjuvanted vaccines. Our data provided support to earlier studies indicating that CaPNP is an attractive vaccine adjuvant and delivery system and should play an important role in the development of safe and efficacious dose-sparing vaccines. Our findings also warrant further investigation to validate CaPNP's capacity as an alternative adjuvant to the ones currently licensed for influenza/pandemic influenza vaccination. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Effect of zymosan and poly (I:C) adjuvants on responses to microneedle immunization coated with whole inactivated influenza vaccine.

    Science.gov (United States)

    Shin, Ju-Hyung; Noh, Jin-Yong; Kim, Kwon-Ho; Park, Jae-Keun; Lee, Ji-Ho; Jeong, Seong Dong; Jung, Dae-Yoon; Song, Chang-Seon; Kim, Yeu-Chun

    2017-11-10

    Microneedles are the micrometer size devices used for the delivery of vaccines and biotherapeutics. In order to increase the vaccine efficacy and reduce the antigen dose, there is a significant need to find some adjuvants for the microneedle vaccination. In this study, zymosan, which is the cell wall preparation of Saccharomyces cerevisiae, or poly (I:C) was coated on a microneedle with inactivated influenza virus, and then immunized into BALB/c mouse to determine the immunogenicity, protection and synergetic effect between two adjuvants. As a result, the group administered with zymosan and vaccine antigen showed significantly stronger IgG response, HI titer and IgG subtypes without any adverse effects, compared to the group immunized with the vaccine antigen alone. Also, there were enhanced cellular immune responses in the group received adjuvant with vaccine antigen. In addition, they showed superior protection and lung viral reduction against lethal viral challenge. Taken together, this study confirms that zymosan can be used as an immunostimulant for microneedle vaccination. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Association of spontaneous abortion with receipt of inactivated influenza vaccine containing H1N1pdm09 in 2010-11 and 2011-12.

    Science.gov (United States)

    Donahue, James G; Kieke, Burney A; King, Jennifer P; DeStefano, Frank; Mascola, Maria A; Irving, Stephanie A; Cheetham, T Craig; Glanz, Jason M; Jackson, Lisa A; Klein, Nicola P; Naleway, Allison L; Weintraub, Eric; Belongia, Edward A

    2017-09-25

    Inactivated influenza vaccine is recommended in any stage of pregnancy, but evidence of safety in early pregnancy is limited, including for vaccines containing A/H1N1pdm2009 (pH1N1) antigen. We sought to determine if receipt of vaccine containing pH1N1 was associated with spontaneous abortion (SAB). We conducted a case-control study over two influenza seasons (2010-11, 2011-12) in the Vaccine Safety Datalink. Cases had SAB and controls had live births or stillbirths and were matched on site, date of last menstrual period, and age. Of 919 potential cases identified using diagnosis codes, 485 were eligible and confirmed by medical record review. Exposure was defined as vaccination with inactivated influenza vaccine before the SAB date; the primary exposure window was the 1-28days before the SAB. The overall adjusted odds ratio (aOR) was 2.0 (95% CI, 1.1-3.6) for vaccine receipt in the 28-day exposure window; there was no association in other exposure windows. In season-specific analyses, the aOR in the 1-28days was 3.7 (95% CI 1.4-9.4) in 2010-11 and 1.4 (95% CI 0.6-3.3) in 2011-12. The association was modified by influenza vaccination in the prior season (post hoc analysis). Among women who received pH1N1-containing vaccine in the previous influenza season, the aOR in the 1-28days was 7.7 (95% CI 2.2-27.3); the aOR was 1.3 (95% CI 0.7-2.7) among women not vaccinated in the previous season. This effect modification was observed in each season. SAB was associated with influenza vaccination in the preceding 28days. The association was significant only among women vaccinated in the previous influenza season with pH1N1-containing vaccine. This study does not and cannot establish a causal relationship between repeated influenza vaccination and SAB, but further research is warranted. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Association between Guillain-Barré syndrome and influenza A (H1N1) 2009 monovalent inactivated vaccines in the USA: a meta-analysis.

    Science.gov (United States)

    Salmon, Daniel A; Proschan, Michael; Forshee, Richard; Gargiullo, Paul; Bleser, William; Burwen, Dale R; Cunningham, Francesca; Garman, Patrick; Greene, Sharon K; Lee, Grace M; Vellozzi, Claudia; Yih, W Katherine; Gellin, Bruce; Lurie, Nicole

    2013-04-27

    The influenza A (H1N1) 2009 monovalent vaccination programme was the largest mass vaccination initiative in recent US history. Commensurate with the size and scope of the vaccination programme, a project to monitor vaccine adverse events was undertaken, the most comprehensive safety surveillance agenda in the USA to date. The adverse event monitoring project identified an increased risk of Guillain-Barré syndrome after vaccination; however, some individual variability in results was noted. Guillain-Barré syndrome is a rare but serious health disorder in which a person's own immune system damages their nerve cells, causing muscle weakness, sometimes paralysis, and infrequently death. We did a meta-analysis of data from the adverse event monitoring project to ascertain whether influenza A (H1N1) 2009 monovalent inactivated vaccines used in the USA increased the risk of Guillain-Barré syndrome. Data were obtained from six adverse event monitoring systems. About 23 million vaccinated people were included in the analysis. The primary analysis entailed calculation of incidence rate ratios and attributable risks of excess cases of Guillain-Barré syndrome per million vaccinations. We used a self-controlled risk-interval design. Influenza A (H1N1) 2009 monovalent inactivated vaccines were associated with a small increased risk of Guillain-Barré syndrome (incidence rate ratio 2·35, 95% CI 1·42-4·01, p=0·0003). This finding translated to about 1·6 excess cases of Guillain-Barré syndrome per million people vaccinated. The modest risk of Guillain-Barré syndrome attributed to vaccination is consistent with previous estimates of the disorder after seasonal influenza vaccination. A risk of this small magnitude would be difficult to capture during routine seasonal influenza vaccine programmes, which have extensive, but comparatively less, safety monitoring. In view of the morbidity and mortality caused by 2009 H1N1 influenza and the effectiveness of the vaccine

  17. Cold adaptation generates mutations associated with the growth of influenza B vaccine viruses.

    Science.gov (United States)

    Kim, Hyunsuh; Velkov, Tony; Camuglia, Sarina; Rockman, Steven P; Tannock, Gregory A

    2015-10-26

    Seasonal inactivated influenza vaccines are usually trivalent or quadrivalent and are prepared from accredited seed viruses. Yields of influenza A seed viruses can be enhanced by gene reassortment with high-yielding donor strains, but similar approaches for influenza B seed viruses have been largely unsuccessful. For vaccine manufacture influenza B seed viruses are usually adapted for high-growth by serial passage. Influenza B antigen yields so obtained are often unpredictable and selection of influenza B seed viruses by this method can be a rate-limiting step in seasonal influenza vaccine manufacture. We recently have shown that selection of stable cold-adapted mutants from seasonal epidemic influenza B viruses is associated with improved growth. In this study, specific mutations were identified that were responsible for growth enhancement as a consequence of adaptation to growth at lower temperatures. Molecular analysis revealed that the following mutations in the HA, NP and NA genes are required for enhanced viral growth: G156/N160 in the HA, E253, G375 in the NP and T146 in the NA genes. These results demonstrate that the growth of seasonal influenza B viruses can be optimized or improved significantly by specific gene modifications. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Adjuvanted influenza vaccine administered intradermally elicits robust long-term immune responses that confer protection from lethal challenge.

    Directory of Open Access Journals (Sweden)

    Maria del P Martin

    2010-05-01

    Full Text Available The respiratory illnesses caused by influenza virus can be dramatically reduced by vaccination. The current trivalent inactivated influenza vaccine is effective in eliciting systemic virus-specific antibodies sufficient to control viral replication. However, influenza protection generated after parenteral immunization could be improved by the induction of mucosal immune responses.Transcutaneous immunization, a non-invasive vaccine delivery method, was used to investigate the quality, duration and effectiveness of the immune responses induced in the presence of inactivated influenza virus co-administered with retinoic acid or oleic acid. We observed an increased migration of dendritic cells to the draining lymph nodes after dermal vaccination. Here we demonstrate that this route of vaccine delivery in combination with certain immunomodulators can induce potent immune responses that result in long-term protective immunity. Additionally, mice vaccinated with inactivated virus in combination with retinoic acid show an enhanced sIgA antibody response, increased number of antibody secreting cells in the mucosal tissues, and protection from a higher influenza lethal dose.The present study demonstrates that transdermal administration of inactivated virus in combination with immunomodulators stimulates dendritic cell migration, results in long-lived systemic and mucosal responses that confer effective protective immunity.

  19. Critical role of TLR7 signaling in the priming of cross-protective cytotoxic T lymphocyte responses by a whole inactivated influenza virus vaccine.

    Directory of Open Access Journals (Sweden)

    Natalija Budimir

    Full Text Available Current influenza vaccines fail to induce protection against antigenically distinct virus strains. Accordingly, there is a need for the development of cross-protective vaccines. Previously, we and others have shown that vaccination with whole inactivated virus (WIV induces cross-protective cellular immunity in mice. To probe the mechanistic basis for this finding, we investigated the role of TLR7, a receptor for single-stranded RNA, in induction of cross-protection. Vaccination of TLR7-/- mice with influenza WIV failed to protect against a lethal heterosubtypic challenge; in contrast, wild-type mice were fully protected. The lack of protection in TLR7-/- mice was associated with high viral load and a relative paucity of influenza-specific CD8+ cytotoxic T lymphocyte (CTL responses. Dendritic cells (DCs from TLR7-/- mice were unable to cross-present WIV-derived antigen to influenza-specific CTLs in vitro. Similarly, TLR7-/- DCs failed to mature and become activated in response to WIV, as determined by the assessment of surface marker expression and cytokine production. Plasmacytoid DCs (pDCs derived from wild-type mice responded directly to WIV while purified conventional DCs (cDCs did not respond to WIV in isolation, but were responsive in mixed pDC/cDC cultures. Depletion of pDCs prior to and during WIV immunization resulted in reduced numbers of influenza-specific CTLs and impaired protection from heterosubtypic challenge. Thus, TLR7 plays a critical role in the induction of cross-protective immunity upon vaccination with WIV. The initial target cells for WIV appear to be pDCs which by direct or indirect mechanisms promote activation of robust CTL responses against conserved influenza epitopes.

  20. Influenza Vaccines: Unmet Needs and Recent Developments

    Science.gov (United States)

    Noh, Ji Yun

    2013-01-01

    Influenza is a worldwide public health concern. Since the introduction of trivalent influenza vaccine in 1978, vaccination has been the primary means of prevention and control of influenza. Current influenza vaccines have moderate efficacy, good safety, and acceptable tolerability; however, they have unsatisfactory efficacy in older adults, are dependent on egg supply for production, and are time-consuming to manufacture. This review outlines the unmet medical needs of current influenza vaccines. Recent developments in influenza vaccines are also described. PMID:24475351

  1. Inactivation of Avian Influenza Viruses on Porous and Non-porous Surfaces is Enhanced by Elevating Absolute Humidity.

    Science.gov (United States)

    Guan, J; Chan, M; VanderZaag, A

    2017-08-01

    This study was to evaluate the effect of absolute humidity (AH), a combined factor of temperature and relative humidity (RH), on inactivation of avian influenza viruses (AIVs) on surfaces. Suspensions of the H9N2 or H6N2 AIV were deposited onto carrier surfaces that were either porous (pine wood) or non-porous (stainless steel, synthetic rubber and glass). The inoculated carriers were incubated at 23, 35 or 45°C with 25% or 55% RH for up to 28 days. After incubation, virus was recovered and quantified by chicken embryo assays. The time required to obtain a log 10 reduction in virus infectivity (D-value) was estimated using a linear regression model. At AH of 5.2 g/m 3 (23°C & 25% RH), both viruses survived up to 14 days on the porous surface and for at least 28 days on the non-porous surfaces. The corresponding D-values for H9N2 and H6N2 were 1.49 and 6.90 days on the porous surface and 7.81 and 12.5 days on the non-porous surfaces, respectively. In comparison, at AH of 9.9 g/m 3 (35°C & 25% RH) or 11.3 g/m 3 (23°C & 55% RH), the D-values for H9N2 and H6N2 dropped to ≤0.76 day on the porous surface and to ≤1.81 days on the non-porous surfaces. As the AH continued to rise from 11.3 to 36.0 g/m 3 , the D-value for both viruses decreased further. The relationship between D-value and AH followed a form of y = ax -b for both viruses. The D-values for H9N2 virus were significantly lower (P < 0.05) than those for H6N2 virus. Exposure to ammonia gas at concentrations of 86 and 173 ppm did not significantly alter test results. The findings give evidence that increasing the AH in poultry buildings following an outbreak of disease could greatly reduce the length of time required for their decontamination. © Her Majesty the Queen in Right of Canada 2016.

  2. H3N2 influenza infection elicits more cross-reactive and less clonally expanded anti-hemagglutinin antibodies than influenza vaccination.

    Directory of Open Access Journals (Sweden)

    M Anthony Moody

    Full Text Available BACKGROUND: During the recent H1N1 influenza pandemic, excess morbidity and mortality was seen in young but not older adults suggesting that prior infection with influenza strains may have protected older subjects. In contrast, a history of recent seasonal trivalent vaccine in younger adults was not associated with protection. METHODS AND FINDINGS: To study hemagglutinin (HA antibody responses in influenza immunization and infection, we have studied the day 7 plasma cell repertoires of subjects immunized with seasonal trivalent inactivated influenza vaccine (TIV and compared them to the plasma cell repertoires of subjects experimentally infected (EI with influenza H3N2 A/Wisconsin/67/2005. The majority of circulating plasma cells after TIV produced influenza-specific antibodies, while most plasma cells after EI produced antibodies that did not react with influenza HA. While anti-HA antibodies from TIV subjects were primarily reactive with single or few HA strains, anti-HA antibodies from EI subjects were isolated that reacted with multiple HA strains. Plasma cell-derived anti-HA antibodies from TIV subjects showed more evidence of clonal expansion compared with antibodies from EI subjects. From an H3N2-infected subject, we isolated a 4-member clonal lineage of broadly cross-reactive antibodies that bound to multiple HA subtypes and neutralized both H1N1 and H3N2 viruses. This broad reactivity was not detected in post-infection plasma suggesting this broadly reactive clonal lineage was not immunodominant in this subject. CONCLUSION: The presence of broadly reactive subdominant antibody responses in some EI subjects suggests that improved vaccine designs that make broadly reactive antibody responses immunodominant could protect against novel influenza strains.

  3. Fever following administration of two inactivated influenza vaccines--a survey of parents of New Zealand infants and children 5 years of age and under.

    Science.gov (United States)

    Petousis-Harris, Helen; Poole, Tracey; Booy, Robert; Turner, Nikki

    2011-04-05

    Due to a dramatic increase in reported febrile convulsions in Western Australia following a routine pediatric influenza vaccination programme we evaluated parental recall of fever in their child following 2010 trivalent influenza vaccine manufactured by either Sanofi Pasteur (Vaxigrip(®)) or CSL Biotherapies (Fluvax(®)) to determine if the rates of febrile events in infants and children 5 years and under following administration of either Vaxigrip(®) or Fluvax(®) were significantly different. A convenience sample of New Zealand General practices who had received stocks of the vaccines of interest consecutively contacted parents of infants and children under 5 years of age who received at least one dose of 2010 influenza vaccine. A brief questionnaire was administered with the main outcome parental recall of fever within 24 h of vaccination. Response rate was 99%. There were 327 parents of children aged 6 months to 5 years attending one of 23 primary care practices who had received a dose of either the Vaxigrip(®) or Fluvax(®) vaccine between 4th March and 28th June 2010 surveyed. A total of 422 doses were given of which 267 were Vaxigrip(®), 133 were Fluvax(®) and 22 another vaccine. Fever occurred significantly more frequently within 24 h following administration of Fluvax(®) compared with Vaxigrip(®) RR 4.33 (2.44-7.70). When fevers were measured they were, on average, higher in the Fluvax(®) vaccines (38°C compared with 39°C). Additionally, recipients were more likely to seek medical advice for fever following Fluvax(®) RR 23.11 (2.96-180.12). There is considerable variation in reactogenicity between two 2010 seasonal vaccines in infants and young children. Vaxigrip(®) is significantly less reactogenic when compared to Fluvax(®) in this population in which Fluvax(®) is associated with unacceptably high rates of febrile reactions. There has been insufficient safety evaluation of seasonal influenza vaccine safety in this population. Copyright

  4. Influenza vaccination in preventing outbreaks in schools: A long-term ecological overview.

    Science.gov (United States)

    Pan, Yang; Wang, Quanyi; Yang, Peng; Zhang, Li; Wu, Shuangsheng; Zhang, Yi; Sun, Ying; Duan, Wei; Ma, Chunna; Zhang, Man; Zhang, Xingxing; MacIntyre, C Raina

    2017-12-18

    Influenza vaccination is the most effective way to reduce the incidence of influenza infections. However, the role of influenza vaccination, such as school-based influenza vaccination, in preventing the influenza outbreaks in schools remains unclear now. In this study, a total of 286 school febrile outbreaks involving 6863 cases in the Beijing area from September 1, 2006 to March 31, 2017 were analyzed. We also tested 294 circulating strains isolated in Beijing during the same period and compared with that of vaccine strains identified every influenza season. The virological match/mismatch between vaccine strains and circulating strains, and the coverage of vaccination in schools were analyzed against outbreaks during the 11 years. It showed that over 80% school febrile outbreaks were caused by influenza A/B virus, the most frequent being A(H3N2) virus (53.25%), followed by A(H1N1)pdm09 virus (25.11%) and B virus (21.64%). More importantly, low vaccine coverage (in 2006-2007 influenza season) and vaccine mismatch (in 2014-2015 and 2015-2016 influenza season) were associated with an increased number of influenza school outbreaks. High vaccination coverage with a matched vaccine can significantly reduce influenza outbreaks in schools (OR: 0.111, p school-based influenza vaccination in preventing outbreaks using trivalent inactivated influenza vaccine in schools. Thus the school-based vaccine policy should be paid more attention in China and other countries worldwide. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Modified live virus vaccine induces a distinct immune response profile compared to inactivated influenza A virus vaccines in swine

    Science.gov (United States)

    Genetic and antigenic diversity within H1 influenza A virus (IAV) subtypes circulating in swine is increasing. The need for cross-protective influenza vaccines in swine is necessary as the virus becomes more diverse. This study compared the humoral and cell-mediated immune response of modified live ...

  6. Evaluations for in vitro correlates of immunogenicity of inactivated influenza a H5, H7 and H9 vaccines in humans.

    Science.gov (United States)

    Couch, Robert B; Decker, William K; Utama, Budi; Atmar, Robert L; Niño, Diane; Feng, Jing Qi; Halpert, Matthew M; Air, Gillian M

    2012-01-01

    Serum antibody responses in humans to inactivated influenza A (H5N1), (H9N2) and A (H7) vaccines have been varied but frequently low, particularly for subunit vaccines without adjuvant despite hemagglutinin (HA) concentrations expected to induce good responses. To help understand the low responses to subunit vaccines, we evaluated influenza A (H5N1), (H9N2), (H7N7) vaccines and 2009 pandemic (H1N1) vaccines for antigen uptake, processing and presentation by dendritic cells to T cells, conformation of vaccine HA in antibody binding assays and gel analyses, HA titers with different red blood cells, and vaccine morphology in electron micrographs (EM). Antigen uptake, processing and presentation of H5, H7, H9 and H1 vaccine preparations evaluated in humans appeared normal. No differences were detected in antibody interactions with vaccine and matched virus; although H7 trimer was not detected in western blots, no abnormalities in the conformation of the HA antigens were identified. The lowest HA titers for the vaccines were vaccine and 1:661 for an H9 vaccine; these vaccines induced the fewest antibody responses. A (H1N1) vaccines were the most immunogenic in humans; intact virus and virus pieces were prominent in EM. A good immunogenic A (H9N2) vaccine contained primarily particles of viral membrane with external HA and NA. A (H5N1) vaccines intermediate in immunogenicity were mostly indistinct structural units with stellates; the least immunogenic A (H7N7) vaccine contained mostly small 5 to 20 nm structures. Antigen uptake, processing and presentation to human T cells and conformation of the HA appeared normal for each inactivated influenza A vaccine. Low HA titer was associated with low immunogenicity and presence of particles or split virus pieces was associated with higher immunogenicity.

  7. Evaluations for in vitro correlates of immunogenicity of inactivated influenza a H5, H7 and H9 vaccines in humans.

    Directory of Open Access Journals (Sweden)

    Robert B Couch

    Full Text Available Serum antibody responses in humans to inactivated influenza A (H5N1, (H9N2 and A (H7 vaccines have been varied but frequently low, particularly for subunit vaccines without adjuvant despite hemagglutinin (HA concentrations expected to induce good responses.To help understand the low responses to subunit vaccines, we evaluated influenza A (H5N1, (H9N2, (H7N7 vaccines and 2009 pandemic (H1N1 vaccines for antigen uptake, processing and presentation by dendritic cells to T cells, conformation of vaccine HA in antibody binding assays and gel analyses, HA titers with different red blood cells, and vaccine morphology in electron micrographs (EM.Antigen uptake, processing and presentation of H5, H7, H9 and H1 vaccine preparations evaluated in humans appeared normal. No differences were detected in antibody interactions with vaccine and matched virus; although H7 trimer was not detected in western blots, no abnormalities in the conformation of the HA antigens were identified. The lowest HA titers for the vaccines were <1:4 for the H7 vaccine and 1:661 for an H9 vaccine; these vaccines induced the fewest antibody responses. A (H1N1 vaccines were the most immunogenic in humans; intact virus and virus pieces were prominent in EM. A good immunogenic A (H9N2 vaccine contained primarily particles of viral membrane with external HA and NA. A (H5N1 vaccines intermediate in immunogenicity were mostly indistinct structural units with stellates; the least immunogenic A (H7N7 vaccine contained mostly small 5 to 20 nm structures.Antigen uptake, processing and presentation to human T cells and conformation of the HA appeared normal for each inactivated influenza A vaccine. Low HA titer was associated with low immunogenicity and presence of particles or split virus pieces was associated with higher immunogenicity.

  8. Adjuvant effects of invariant NKT cell ligand potentiates the innate and adaptive immunity to an inactivated H1N1 swine influenza virus vaccine in pigs.

    Science.gov (United States)

    Dwivedi, Varun; Manickam, Cordelia; Dhakal, Santosh; Binjawadagi, Basavaraj; Ouyang, Kang; Hiremath, Jagadish; Khatri, Mahesh; Hague, Jacquelyn Gervay; Lee, Chang Won; Renukaradhya, Gourapura J

    2016-04-15

    Pigs are considered as the source of some of the emerging human flu viruses. Inactivated swine influenza virus (SwIV) vaccine has been in use in the US swine herds, but it failed to control the flu outbreaks. The main reason has been attributed to lack of induction of strong local mucosal immunity in the respiratory tract. Invariant natural killer T (iNKT) cell is a unique T cell subset, and activation of iNKT cell using its ligand α-Galactosylceramide (α-GalCer) has been shown to potentiate the cross-protective immunity to inactivated influenza virus vaccine candidates in mice. Recently, we discovered iNKT cell in pig and demonstrated its activation using α-GalCer. In this study, we evaluated the efficacy of an inactivated H1N1 SwIV coadministered with α-GalCer intranasally against a homologous viral challenge. Our results demonstrated the potent adjuvant effects of α-GalCer in potentiating both innate and adaptive immune responses to SwIV Ags in the lungs of pigs, which resulted in reduction in the lung viral load by 3 logs compared to without adjuvant. Immunologically, in the lungs of pigs vaccinated with α-GalCer an increased virus specific IgA response, IFN-α secretion and NK cell-cytotoxicity was observed. In addition, iNKT cell-stimulation enhanced the secretion of Th1 cytokines (IFN-γ and IL-12) and reduced the production of immunosuppressive cytokines (IL-10 and TGF-β) in the lungs of pigs⋅ In conclusion, we demonstrated for the first time iNKT cell adjuvant effects in pigs to SwIV Ags through augmenting the innate and adaptive immune responses in the respiratory tract. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Superior immunogenicity of inactivated whole virus H5N1 influenza vaccine is primarily controlled by Toll-like receptor signalling.

    Directory of Open Access Journals (Sweden)

    Felix Geeraedts

    2008-08-01

    Full Text Available In the case of an influenza pandemic, the current global influenza vaccine production capacity will be unable to meet the demand for billions of vaccine doses. The ongoing threat of an H5N1 pandemic therefore urges the development of highly immunogenic, dose-sparing vaccine formulations. In unprimed individuals, inactivated whole virus (WIV vaccines are more immunogenic and induce protective antibody responses at a lower antigen dose than other formulations like split virus (SV or subunit (SU vaccines. The reason for this discrepancy in immunogenicity is a long-standing enigma. Here, we show that stimulation of Toll-like receptors (TLRs of the innate immune system, in particular stimulation of TLR7, by H5N1 WIV vaccine is the prime determinant of the greater magnitude and Th1 polarization of the WIV-induced immune response, as compared to SV- or SU-induced responses. This TLR dependency largely explains the relative loss of immunogenicity in SV and SU vaccines. The natural pathogen-associated molecular pattern (PAMP recognized by TLR7 is viral genomic ssRNA. Processing of whole virus particles into SV or SU vaccines destroys the integrity of the viral particle and leaves the viral RNA prone to degradation or involves its active removal. Our results show for a classic vaccine that the acquired immune response evoked by vaccination can be enhanced and steered by the innate immune system, which is triggered by interaction of an intrinsic vaccine component with a pattern recognition receptor (PRR. The insights presented here may be used to further improve the immune-stimulatory and dose-sparing properties of classic influenza vaccine formulations such as WIV, and will facilitate the development of new, even more powerful vaccines to face the next influenza pandemic.

  10. A phase I randomized, double-blind, controlled trial of 2009 influenza A (H1N1) inactivated monovalent vaccines with different adjuvant systems.

    Science.gov (United States)

    Precioso, Alexander R; Miraglia, João L; Campos, Lúcia Maria A; Goulart, Alessandra C; Timenetsky, Maria do Carmo S T; Cardoso, Maria Regina A; Luna, Expedito; Mondini, Gabriella; Guedes, José da S; Raw, Isaias

    2011-11-08

    We conducted a phase I, multicenter, randomized, double-blind, placebo-controlled, multi-arm (10) parallel study involving healthy adults to evaluate the safety and immunogenicity of influenza A (H1N1) 2009 non-adjuvanted and adjuvanted candidate vaccines. Subjects received two intramuscular injections of one of the candidate vaccines administered 21 days apart. Antibody responses were measured by means of hemagglutination-inhibition assay before and 21 days after each vaccination. The three co-primary immunogenicity end points were the proportion of seroprotection >70%, seroconversion >40%, and the factor increase in the geometric mean titer >2.5. A total of 266 participants were enrolled into the study. No deaths or serious adverse events were reported. The most commonly solicited local and systemic adverse events were injection-site pain and headache, respectively. Only three subjects (1.1%) reported severe injection-site pain. Four 2009 influenza A (H1N1) inactivated monovalent candidate vaccines that met the three requirements to evaluate influenza protection, after a single dose, were identified: 15 μg of hemagglutinin antigen without adjuvant; 7.5 μg of hemagglutinin antigen with aluminum hydroxide, MPL and squalene; 3.75 μg of hemagglutinin antigen with aluminum hydroxide and MPL; and 3.75 μg of hemagglutinin antigen with aluminum hydroxide and squalene. Adjuvant systems can be safely used in influenza vaccines, including the adjuvant monophosphoryl lipid A (MPL) derived from Bordetella pertussis with squalene and aluminum hydroxide, MPL with aluminum hydroxide, and squalene and aluminum hydroxide. Copyright © 2011 Elsevier Ltd. All rights reserved.

  11. Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices - United States, 2017-18 Influenza Season.

    Science.gov (United States)

    Grohskopf, Lisa A; Sokolow, Leslie Z; Broder, Karen R; Walter, Emmanuel B; Bresee, Joseph S; Fry, Alicia M; Jernigan, Daniel B

    2017-08-25

    This report updates the 2016-17 recommendations of the Advisory Committee on Immunization Practices (ACIP) regarding the use of seasonal influenza vaccines (MMWR Recomm Rep 2016;65[No. RR-5]). Routine annual influenza vaccination is recommended for all persons aged ≥6 months who do not have contraindications. A licensed, recommended, and age-appropriate vaccine should be used.For the 2017-18 season, quadrivalent and trivalent influenza vaccines will be available. Inactivated influenza vaccines (IIVs) will be available in trivalent (IIV3) and quadrivalent (IIV4) formulations. Recombinant influenza vaccine (RIV) will be available in trivalent (RIV3) and quadrivalent (RIV4) formulations. Live attenuated influenza vaccine (LAIV4) is not recommended for use during the 2017-18 season due to concerns about its effectiveness against (H1N1)pdm09 viruses during the 2013-14 and 2015-16 seasons. Recommendations for different vaccine types and specific populations are discussed. No preferential recommendation is made for one influenza vaccine product over another for persons for whom more than one licensed, recommended product is available.Updates to the recommendations described in this report reflect discussions during public meetings of ACIP held on October 20, 2016; February 22, 2017; and June 21, 2017. New and updated information in this report includes the following:•Vaccine viruses included in the 2017-18 U.S. trivalent influenza vaccines will be an A/Michigan/45/2015 (H1N1)pdm09-like virus, an A/Hong Kong/4801/2014 (H3N2)-like virus, and a B/Brisbane/60/2008-like virus (Victoria lineage). Quadrivalent influenza vaccines will contain these three viruses and an additional influenza B vaccine virus, a B/Phuket/3073/2013-like virus (Yamagata lineage).• Information on recent licensures and labelling changes is discussed, including licensure of Afluria Quadrivalent (IIV4; Seqirus, Parkville, Victoria, Australia); Flublok Quadrivalent (RIV4; Protein Sciences, Meriden

  12. Potency of an inactivated influenza vaccine prepared from A/duck/Mongolia/119/2008 (H7N9) against the challenge with A/Anhui/1/2013 (H7N9).

    Science.gov (United States)

    Chu, Duc-Huy; Sakoda, Yoshihiro; Nishi, Tatsuya; Hiono, Takahiro; Shichinohe, Shintaro; Okamatsu, Masatoshi; Kida, Hiroshi

    2014-06-12

    H7N9 influenza virus infection in humans was reported in China on March 31, 2013. Humans are immunologically naïve to the H7N9 subtype, for which the seasonal influenza vaccine is not effective. Thus, the development of an H7N9 influenza virus vaccine is an urgent issue. To prepare for the emergence of an influenza pandemic, we have established a library comprising more than 1300 influenza virus strains with 144 different combinations of 16 HA and 9 NA subtypes. An H7N9 virus strain isolated from a 35-year-old woman, A/Anhui/1/2013 (H7N9), was found to be antigenically similar to H7N9 influenza viruses isolated from migratory ducks. In the present study, the potency of an inactivated whole virus particle vaccine prepared from an H7N9 low pathogenic avian influenza virus, A/duck/Mongolia/119/2008 (H7N9), selected from the library, was assessed by a challenge with A/Anhui/1/2013 (H7N9). The results indicate that the test vaccine was potent enough to induce sufficient immunity to reduce the impact of disease caused by the challenge with A/Anhui/1/2013 (H7N9) in mice. The present results indicate that an inactivated whole virus particle vaccine prepared from an influenza virus strain stored in the library could be useful as a vaccine strain in case of an influenza pandemic. Copyright © 2014. Published by Elsevier Ltd.

  13. Influenza

    Directory of Open Access Journals (Sweden)

    Forleo-Neto Eduardo

    2003-01-01

    Full Text Available A influenza (gripe é doença infecciosa aguda de origem viral que acomete o trato respiratório e a cada inverno atinge mais de 100 milhões de pessoas na Europa, Japão e Estados Unidos, causando anualmente a morte de cerca de 20 a 40 mil pessoas somente neste último país. O agente etiológico é o Myxovirus influenzae, ou vírus da gripe. Este subdivide-se nos tipos A, B e C, sendo que apenas os do tipo A e B apresentam relevância clínica em humanos. O vírus influenza apresenta altas taxas de mutação, o que resulta freqüentemente na inserção de novas variantes virais na comunidade, para as quais a população não apresenta imunidade. São poucas as opções disponíveis para o controle da influenza. Dentre essas, a vacinação constitui a forma mais eficaz para o controle da doença e de suas complicações. Em função das mutações que ocorrem naturalmente no vírus influenza, recomenda-se que a vacinação seja realizada anualmente. No Brasil, segundo dados obtidos pelo Projeto VigiGripe - ligado à Universidade Federal de São Paulo -, verifica-se que a influenza apresenta pico de atividade entre os meses de maio e setembro. Assim, a época mais indicada para a vacinação corresponde aos meses de março e abril. Para o tratamento específico da influenza estão disponíveis quatro medicamentos antivirais: os fármacos clássicos amantadina e rimantidina e os antivirais de segunda geração oseltamivir e zanamivir. Os últimos, acrescentam alternativas para o tratamento da influenza e ampliam as opções disponíveis para o seu controle.

  14. Standardization of an inactivated H17N1 avian influenza vaccine and efficacy against A/Chicken/Italy/13474/99 high-pathogenicity virus infection.

    Science.gov (United States)

    Di Trani, L; Cordioli, P; Falcone, E; Lombardi, G; Moreno, A; Sala, G; Tollis, M

    2003-01-01

    The minimum requirements for assessing the immunogenicity of an experimental avian influenza (AI) vaccine prepared from inactivated A/Turkey/Italy/2676/99 (H7N1) low-pathogenicity (LP) AI (LPAI) virus were determined in chickens of different ages. A correlation between the amount of hemagglutinin (HA) per dose of vaccine and the protection against clinical signs of disease and infection by A/Chicken/Italy/13474/99 highly pathogenic (HP) AI (HPAI) virus was established. Depending on the vaccination schedule, one or two administrations of 0.5 microg of hemagglutinin protected chickens against clinical signs and death and completely prevented virus shedding from birds challenged at different times after vaccination.

  15. Efficacy of inactivated influenza vaccines for protection of poultry against the H7N9 low pathogenic avian influenza virus isolated in China during 2013

    Science.gov (United States)

    The recent outbreak in China of avian influenza (AI) H7N9 in birds and humans underscores the interspecies movement of these viruses. Interestingly, the genetic composition of these H7N9 viruses appears to be solely of avian origin and of low pathogenicity in birds. Although few isolations of these ...

  16. Protection against H7N3 high pathogenicity avian influenza in chickens immunized with a recombinant fowlpox and an inactivated avian influenza vaccines

    Science.gov (United States)

    Beginning on June 2012, an H7N3 highly pathogenic avian influenza (HPAI) epizootic was reported in the State of Jalisco (Mexico), with some 22.4 million chickens that died, were slaughtered on affected farms or were preemptively culled on neighboring farms. In the current study, layer chickens were ...

  17. Protection of poultry against the 2012 Mexican H7N3 highly pathogenic avian influenza virus with inactivated H7 avian influenza vaccines

    Science.gov (United States)

    In June of 2012, an outbreak of highly pathogenic avian influenza (HPAI) H7N3 was reported poultry in Jalisco, Mexico. Since that time the virus has spread to the surrounding States of Guanajuato and Aguascalientes and new outbreaks continue to be reported. To date more than 25 million birds have di...

  18. Bacterium-like particles supplemented with inactivated influenza antigen induce cross-protective influenza-specific antibody responses through intranasal administration

    NARCIS (Netherlands)

    de Haan, Aalzen; Haijema, Bert Jan; Voorn, Petra; Meijerhof, Tjarko; van Roosmalen, Maarten L.; Leenhouts, Kees

    2012-01-01

    Administration of influenza vaccines through the intranasal (IN) route forms an attractive alternative to conventional intramuscular (IM) injection. It is not only a better accepted form of vaccine administration but it also has the potential to induce, in addition to systemic antibodies, local

  19. Intranasal immunization with a formalin-inactivated human influenza A virus whole-virion vaccine alone and intranasal immunization with a split-virion vaccine with mucosal adjuvants show similar levels of cross-protection.

    Science.gov (United States)

    Okamoto, Shigefumi; Matsuoka, Sumiko; Takenaka, Nobuyuki; Haredy, Ahmad M; Tanimoto, Takeshi; Gomi, Yasuyuki; Ishikawa, Toyokazu; Akagi, Takami; Akashi, Mitsuru; Okuno, Yoshinobu; Mori, Yasuko; Yamanishi, Koichi

    2012-07-01

    The antigenicity of seasonal human influenza virus changes continuously; thus, a cross-protective influenza vaccine design needs to be established. Intranasal immunization with an influenza split-virion (SV) vaccine and a mucosal adjuvant induces cross-protection; however, no mucosal adjuvant has been assessed clinically. Formalin-inactivated intact human and avian viruses alone (without adjuvant) induce cross-protection against the highly pathogenic H5N1 avian influenza virus. However, it is unknown whether seasonal human influenza formalin-inactivated whole-virion (WV) vaccine alone induces cross-protection against strains within a subtype or in a different subtype of human influenza virus. Furthermore, there are few reports comparing the cross-protective efficacy of the WV vaccine and SV vaccine-mucosal adjuvant mixtures. Here, we found that the intranasal human influenza WV vaccine alone induced both the innate immune response and acquired immune response, resulting in cross-protection against drift variants within a subtype of human influenza virus. The cross-protective efficacy conferred by the WV vaccine in intranasally immunized mice was almost the same as that conferred by a mixture of SV vaccine and adjuvants. The level of cross-protective efficacy was correlated with the cross-reactive neutralizing antibody titer in the nasal wash and bronchoalveolar fluids. However, neither the SV vaccine with adjuvant nor the WV vaccine induced cross-reactive virus-specific cytotoxic T-lymphocyte activity. These results suggest that the intranasal human WV vaccine injection alone is effective against variants within a virus subtype, mainly through a humoral immune response, and that the cross-protection elicited by the WV vaccine and the SV vaccine plus mucosal adjuvants is similar.

  20. The effect of gamma-irradiation conditions on the immunogenicity of whole-inactivated Influenza A virus vaccine.

    Science.gov (United States)

    David, Shannon C; Lau, Josyane; Singleton, Eve V; Babb, Rachelle; Davies, Justin; Hirst, Timothy R; McColl, Shaun R; Paton, James C; Alsharifi, Mohammed

    2017-02-15

    Gamma-irradiation, particularly an irradiation dose of 50kGy, has been utilised widely to sterilise highly pathogenic agents such as Ebola, Marburg Virus, and Avian Influenza H5N1. We have reported previously that intranasal vaccination with a gamma-irradiated Influenza A virus vaccine (γ-Flu) results in cross-protective immunity. Considering the possible inclusion of highly pathogenic Influenza strains in future clinical development of γ-Flu, an irradiation dose of 50kGy may be used to enhance vaccine safety beyond the internationally accepted Sterility Assurance Level (SAL). Thus, we investigated the effect of irradiation conditions, including high irradiation doses, on the immunogenicity of γ-Flu. Our data confirm that irradiation at low temperatures (using dry-ice) is associated with reduced damage to viral structure compared with irradiation at room temperature. In addition, a single intranasal vaccination with γ-Flu irradiated on dry-ice with either 25 or 50kGy induced seroconversion and provided complete protection against lethal Influenza A challenge. Considering that low temperature is expected to reduce the protein damage associated with exposure to high irradiation doses, we titrated the vaccine dose to verify the efficacy of 50kGy γ-Flu. Our data demonstrate that exposure to 50kGy on dry-ice is associated with limited effect on vaccine immunogenicity, apparent only when using very low vaccine doses. Overall, our data highlight the immunogenicity of influenza virus irradiated at 50kGy for induction of high titre antibody and cytotoxic T-cell responses. This suggests these conditions are suitable for development of γ-Flu vaccines based on highly pathogenic Influenza A viruses. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Technology transfer of oil-in-water emulsion adjuvant manufacturing for pandemic influenza vaccine production in Romania: Preclinical evaluation of split virion inactivated H5N1 vaccine with adjuvant.

    Science.gov (United States)

    Stavaru, Crina; Onu, Adrian; Lupulescu, Emilia; Tucureanu, Catalin; Rasid, Orhan; Vlase, Ene; Coman, Cristin; Caras, Iuliana; Ghiorghisor, Alina; Berbecila, Laurentiu; Tofan, Vlad; Bowen, Richard A; Marlenee, Nicole; Hartwig, Airn; Bielefeldt-Ohmann, Helle; Baldwin, Susan L; Van Hoeven, Neal; Vedvick, Thomas S; Huynh, Chuong; O'Hara, Michael K; Noah, Diana L; Fox, Christopher B

    2016-04-02

    Millions of seasonal and pandemic influenza vaccine doses containing oil-in-water emulsion adjuvant have been administered in order to enhance and broaden immune responses and to facilitate antigen sparing. Despite the enactment of a Global Action Plan for Influenza Vaccines and a multi-fold increase in production capabilities over the past 10 years, worldwide capacity for pandemic influenza vaccine production is still limited. In developing countries, where routine influenza vaccination is not fully established, additional measures are needed to ensure adequate supply of pandemic influenza vaccines without dependence on the shipment of aid from other, potentially impacted first-world countries. Adaptation of influenza vaccine and adjuvant technologies by developing country influenza vaccine manufacturers may enable antigen sparing and corresponding increases in global influenza vaccine coverage capacity. Following on previously described work involving the technology transfer of oil-in-water emulsion adjuvant manufacturing to a Romanian vaccine manufacturing institute, we herein describe the preclinical evaluation of inactivated split virion H5N1 influenza vaccine with emulsion adjuvant, including immunogenicity, protection from virus challenge, antigen sparing capacity, and safety. In parallel with the evaluation of the bioactivity of the tech-transferred adjuvant, we also describe the impact of concurrent antigen manufacturing optimization activities. Depending on the vaccine antigen source and manufacturing process, inclusion of adjuvant was shown to enhance and broaden functional antibody titers in mouse and rabbit models, promote protection from homologous virus challenge in ferrets, and facilitate antigen sparing. Besides scientific findings, the operational lessons learned are delineated in order to facilitate adaptation of adjuvant technologies by other developing country institutes to enhance global pandemic influenza preparedness.

  2. Thermal inactivation of avian influenza virus and Newcastle disease virus in a fat-free egg product

    Science.gov (United States)

    Avian influenza (AI) and Avian Paramyxovirus Type-1 (AMPV-1) viruses can survive on the carcasses, in organ tissue of infected birds, on fomites, and have the potential for egg transmission and egg product contamination. With the increase in global trade, there are concerns that egg products could ...

  3. Updated recommendations for heat inactivation of high pathogenicity avian influenza virus in dried egg white for import/export purposes

    Science.gov (United States)

    High pathogenicity avian influenza viruses (HPAIV) cause severe systemic disease with high mortality in chickens. Isolation of HPAIV from the internal contents of chicken eggs has been reported, and this is cause for concern because HPAIV can be spread by movement of poultry products during marketi...

  4. The impact of pandemic A(H1N1)pdm09 influenza and vaccine-associated adverse events on parental attitudes and influenza vaccine uptake in young children.

    Science.gov (United States)

    Blyth, Christopher C; Richmond, Peter C; Jacoby, Peter; Thornton, Patrick; Regan, Annette; Robins, Christine; Kelly, Heath; Smith, David W; Effler, Paul V

    2014-07-07

    Parental attitudes towards vaccination significantly influence vaccine uptake. The A(H1N1)pdm09 influenza pandemic was followed in 2010 by an unprecedented increase in febrile reactions in children receiving trivalent inactivated influenza vaccine manufactured by bioCSL. Uptake of TIV in children vaccination is uncertain. A parental attitudes survey towards influenza illness and vaccination was conducted as part of the West Australian Influenza Vaccine Effectiveness study. Vaccination status was assessed by parental interview and confirmed by the national register and/or vaccine providers. Parental attitudes from vaccinated and unvaccinated children and attitudes in 2008-2009 and 2010-2012 were compared. Principal Component Analysis was conducted to determine core attitudes that influenced vaccine uptake. Vaccination history and parental attitude surveys were available from 2576 children. Parents of fully vaccinated children less frequently stated that influenza was a mild disease, more frequently stated that influenza vaccine was safe and were less frequently worried about vaccine side effects. Uptake of influenza vaccine decreased significantly from 2010 onwards. From 2010, parents were less concerned about severe influenza, but more concerned about vaccine side effects and safety. Despite this significant shift in attitudes towards influenza vaccine, parental acceptance of vaccines on the national immunisation program did not change. Principal Component Analysis revealed that attitudes around vaccine safety and efficacy were the most important attitudes impacting on vaccine uptake. Parental attitudes to influenza vaccine changed from 2010. Confidence in the WA preschool influenza vaccination program remains low yet appeared unchanged for other vaccines. Restoring public confidence in childhood influenza vaccination is needed before uptake can be improved. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Assessment of the removal and inactivation of influenza viruses H5N1 and H1N1 by drinking water treatment.

    Science.gov (United States)

    Lénès, Dorothée; Deboosere, Nathalie; Ménard-Szczebara, Florence; Jossent, Jérôme; Alexandre, Virginie; Machinal, Claire; Vialette, Michèle

    2010-04-01

    inactivation (more than a 5-log inactivation with a UV dose of 25 mJ/cm2). Of the chemical disinfection treatments, ozone, chlorine and chlorine dioxide were all very effective in inactivating H5N1 and H1N1, whereas monochloramine treatment required higher doses and longer contact times to achieve significant reductions. Our findings suggest that the water treatment strategies that are currently used for surface water treatment are entirely suitable for removing and/or inactivating influenza A viruses. Appropriate preventive actions can be defined for single disinfection treatment plants. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  6. Parents' preferences for seasonal influenza vaccine for their children in Japan.

    Science.gov (United States)

    Shono, Aiko; Kondo, Masahide

    2014-09-03

    In Japan, trivalent inactivated influenza vaccine is the only approved influenza vaccine. It is typically administrated by hypodermic injection, and children under 13 years of age are recommended to be vaccinated two times during each winter season. Live-attenuated influenza vaccine (LAIV) is administered by a thimerosal-free nasal spray. If LAIV is approved in the future in Japan, parents will have an alternative type of influenza vaccine for their children. This study investigated parents' preference for the type of seasonal influenza vaccine for their children if alternatives are available. The marginal willingness to pay for vaccine benefits was also evaluated. We conducted a discrete choice experiment, a quantitative approach that is often used in healthcare studies, in January 2013. Respondents were recruited from a registered online survey panel, and parents with at least one child under 13 years of age were offered questionnaires. This study showed that for seasonal influenza vaccines for their children, parents are more likely to value safety, including thimerosal-free vaccines and those with a lower risk of adverse events, instead of avoiding the momentary pain from an injection. If LAIV is released in Japan, the fact that it is thimerosal-free could be an advantage. However, for parents to choose LAIV, they would need to accept the slightly higher risk of minor adverse events from LAIV. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Retrospective public health impact of a quadrivalent influenza vaccine in the United States over the period 2000-2014

    NARCIS (Netherlands)

    Crépey, P.; De Boer, P.; Postma, M.J.; Pitman, R.J.

    2014-01-01

    Objectives: Vaccination has proven to be an efficient preventive strategy against influenza infection. Each year, two genetically distinct influenza B lineages cocirculate. Current trivalent influenza vaccines (TIVs) contain only one influenza B and two influenza A strains, but vaccine mismatch are

  8. Mutagenesis and ultraviolet inactivation of transforming DNA of ''Haemophilus influenzae'' complexed with a ''Bacillus subtilis'' protein that alter DNA conformation

    International Nuclear Information System (INIS)

    Setlow, Jane K.; Setlow, Barbara C.; Setlow, Peter

    1996-01-01

    The wild-type ''Bacillus subtilis'' spore protein, SspC wt , binds to DNA ''in vitro'' and ''in vivo'' and changes the conformation of DNA from B to A. Synthesis of the cloned SspC wt gene in ''Escherichia coli'' also causes large increases in mutation frequency. Binding of SspC wt to transforming DNA from ''Haemophilus influenzae'' made the DNA resistant to ultraviolet (UV) radiation. The mutant protein, SspC ala , which does not bind DNA, did not change the UV resistance. The UV sensitivity of the DNA/SspC wt complex was not increased when the recipients of the DNA were defective in excision of pyrimidine dimers. These data indicate that the ''H. influenzae'' excision mechanism does not operate on the spore photoproduct formed by UV irradiation of the complex. Selection for the streptomycin- or erythromycin-resistance markers on the transforming DNA evidenced significant mutations at loci closely linked to these, but not at other loci. SspC wt apparently entered the cell attached to the transforming DNA, and caused mutations in adjacent loci. The amount of such mutations decreased when the transforming DNA was UV irradiated, because UV unlinks linked markers. (author). 22 refs, 4 figs, 4 tabs

  9. Mutagenesis and ultraviolet inactivation of transforming DNA of ``Haemophilus influenzae`` complexed with a ``Bacillus subtilis`` protein that alter DNA conformation

    Energy Technology Data Exchange (ETDEWEB)

    Setlow, Jane K. [Brookhaven National Lab., Upton, NY (United States); Setlow, Barbara C.; Setlow, Peter [Connecticut Univ., Farmington, CT (United States)

    1996-12-31

    The wild-type ``Bacillus subtilis`` spore protein, SspC{sup wt}, binds to DNA ``in vitro`` and ``in vivo`` and changes the conformation of DNA from B to A. Synthesis of the cloned SspC{sup wt} gene in ``Escherichia coli`` also causes large increases in mutation frequency. Binding of SspC{sup wt} to transforming DNA from ``Haemophilus influenzae`` made the DNA resistant to ultraviolet (UV) radiation. The mutant protein, SspC{sup ala}, which does not bind DNA, did not change the UV resistance. The UV sensitivity of the DNA/SspC{sup wt} complex was not increased when the recipients of the DNA were defective in excision of pyrimidine dimers. These data indicate that the ``H. influenzae`` excision mechanism does not operate on the spore photoproduct formed by UV irradiation of the complex. Selection for the streptomycin- or erythromycin-resistance markers on the transforming DNA evidenced significant mutations at loci closely linked to these, but not at other loci. SspC{sup wt} apparently entered the cell attached to the transforming DNA, and caused mutations in adjacent loci. The amount of such mutations decreased when the transforming DNA was UV irradiated, because UV unlinks linked markers. (author). 22 refs, 4 figs, 4 tabs.

  10. [Immunogenicity of inactivated subunit adsorbed monovalent vaccine against influenza A/California/7/2009 (H1N1) strain].

    Science.gov (United States)

    Zverev, V V; Kostinov, M P; Mikhailova, N A; Zhirova, S N; Mironov, A N; Terkacheva, O A; Romanova, A A; Cherdantsev, A P

    2011-01-01

    The immunogenicity of Pandeflu subunit vaccine against influenza A/California/7/2009 (H1N1) was evaluated in 70 healthy volunteers aged 18 to 60 years. The vaccine was intramuscularly injected twice at an interval of 28 days. Each dose (0.5 ml) contains A(HIN1) influenza virus hemagglutinin (15 +/- 2.2 microg), aluminum hydroxide (Denmark) (0.475 +/- 0.075 microg), and the preservative thiomerosal (merthiolate) (50 +/- 7.5 microg). The level of antibodies was determined in the microneutralization assay. After administration of two doses of the vaccine at a 28-day interval, the geometric mean antibody titer (GMAT) reached 1:21.1 with a further increase to 1:30 (the baseline GMAT) was 1:6.1). The frequencies of seroconversion and seroprotection were 71.4 and 59.2%, respectively; the antibody increase factor was 4.92, which meets the CPMP criteria. The administration of the vaccine did not result in adverse reactions in the postvaccination period.

  11. Application of electrolysis for inactivation of an antiviral drug that is one of possible selection pressure to drug-resistant influenza viruses.

    Science.gov (United States)

    Kobayashi, Toyohide; Hirose, Jun; Wu, Hong; Sano, Kouichi; Katsumata, Takahiro; Tsujibo, Hiroshi; Nakano, Takashi

    2013-12-01

    The recent development of antiviral drugs has led to concern that the release of the chemicals in surface water due to expanded medical use could induce drug-resistant mutant viruses in zoonosis. Many researchers have noted that the appearance of an oseltamivir (Tamiflu(®))-resistant avian influenza mutant virus, which may spread to humans, could be induced by oseltamivir contamination of surface water. Although past studies have reported electrolysis as a possible method for degradation of antineoplastics and antibacterials in water, the validity of the method for treatment of antiviral drugs is unknown. In this study, electrolysis was used to degrade an antiviral prodrug, oseltamivir, and a stable active form, oseltamivir carboxylate, and the degradation process was monitored with HPLC-UV and the neuraminidase inhibitory assay. HPLC-UV-detectable oseltamivir and oseltamivir carboxylate were decomposed by electrolysis within 60 min, and inhibitory activity of neuraminidase decreased below the detection limit of the assay used. Cytotoxic and genotoxic activity were not detected in electrolyzed fluid. These results indicate that electrolysis is a possible treatment for inactivation of the antiviral drug oseltamivir. Copyright © 2013 Elsevier B.V. All rights reserved.

  12. Efficacy of two H5N9-inactivated vaccines against challenge with a recent H5N1 highly pathogenic avian influenza isolate from a chicken in Thailand.

    Science.gov (United States)

    Bublot, Michel; Le Gros, François-Xavier; Nieddu, Daniela; Pritchard, Nikki; Mickle, Thomas R; Swayne, David E

    2007-03-01

    The objective of this study was to compare the efficacy of two avian influenza (AI) H5-inactivated vaccines containing either an American (A/turkey/Wisconsin/68 H5N9; H5N9-WI) or a Eurasian isolate (A/chicken/Italy/22A/98 H5N9; H5N9-It). Three-week-old specific pathogen-free chickens were vaccinated once and challenged 3 wk later with a H5N1 highly pathogenic AI (HPAI) virus isolated from a chicken in Thailand in 2004. All unvaccinated challenged birds died within 2 days, whereas 90% and 100% of chickens vaccinated with H5N9-WI and H5N9-It, respectively, were protected against morbidity and mortality. Both vaccines prevented cloacal shedding and significantly reduced oral shedding of the challenge HPAI virus. Additional chickens (vaccinated or unvaccinated) were placed in contact with the directly challenged birds 18 hr after challenge. All unvaccinated chickens in contact with unvaccinated challenged birds died within 3 days after contact, whereas unvaccinated chickens in contact with vaccinated challenged birds either showed a significantly delayed mortality or did not become infected. All vaccinated contacts were protected against clinical signs, and most chickens did not shed detectable amount of HPAI virus. Altogether, these data indicate that both vaccines protected very well against morbidity and mortality and reduced or prevented shedding induced by direct or contact exposure to Asian H5N1 HPAI virus.

  13. [Vaccination against influenza in pregnant women - safety and effectiveness].

    Science.gov (United States)

    Nitsch-Osuch, Aneta; Woźniak Kosek, Agnieszka; Brydak, Lidia Bernadeta

    2013-01-01

    Influenza is a major cause of morbidity and mortality worldwide. During seasonal influenza epidemics and pandemics, pregnancy places otherwise healthy women at an increased risk of complications from influenza. The factors believed to increase the susceptibility of complicated influenza infection during pregnancy are linked to the physiologic changes, including immunologic changes (attenuation of the cell-mediated immune responses, selective suppression of T-helper 1 cell mediated immunity while the adaptive humoral immunity remains unimpaired), increased cardiac output and oxygen consumption and tidal volume. Pregnant women have similar incidence of seasonal influenza as the general population, however because of the physiological changes, they are at an increased risk of complications (including secondary pneumonia, acute respiratory insufficiency increased risk of stillbirth, premature deliveries) and death. Immunization of pregnant women against influenza is currently recommended in many countries. Vaccination against influenza with trivalent inactivated vaccine (TIV) has been proven to be safe and effective. Lack of harmful effect of TIV on pregnant women and newborns has been demonstrated in several studies: no increased risk of spontaneous abortions, preterm birth, low birth weight, congenital malformations, cesarean section have been reported. Vaccination against influenza has been proven to be effective in reducing rates and severity of the disease in vaccinated mothers and their children. Several studies revealed a decreased risk of influenza-like illnesses among mothers who were vaccinated during pregnancy but also a decreased risk of laboratory confirmed cases of influenza and hospitalizations due to influenza and its complications among newborns and infants born to vaccinated mothers. Currently available inactivated influenza vaccines are not licensed for use in infants younger than 6 months. Protection of young infants against the infection in early

  14. The safety, immunogenicity, and acceptability of inactivated influenza vaccine delivered by microneedle patch (TIV-MNP 2015): a randomised, partly blinded, placebo-controlled, phase 1 trial.

    Science.gov (United States)

    Rouphael, Nadine G; Paine, Michele; Mosley, Regina; Henry, Sebastien; McAllister, Devin V; Kalluri, Haripriya; Pewin, Winston; Frew, Paula M; Yu, Tianwei; Thornburg, Natalie J; Kabbani, Sarah; Lai, Lilin; Vassilieva, Elena V; Skountzou, Ioanna; Compans, Richard W; Mulligan, Mark J; Prausnitz, Mark R

    2017-08-12

    Microneedle patches provide an alternative to conventional needle-and-syringe immunisation, and potentially offer improved immunogenicity, simplicity, cost-effectiveness, acceptability, and safety. We describe safety, immunogenicity, and acceptability of the first-in-man study on single, dissolvable microneedle patch vaccination against influenza. The TIV-MNP 2015 study was a randomised, partly blinded, placebo-controlled, phase 1, clinical trial at Emory University that enrolled non-pregnant, immunocompetent adults from Atlanta, GA, USA, who were aged 18-49 years, naive to the 2014-15 influenza vaccine, and did not have any significant dermatological disorders. Participants were randomly assigned (1:1:1:1) to four groups and received a single dose of inactivated influenza vaccine (fluvirin: 18 μg of haemagglutinin per H1N1 vaccine strain, 17 μg of haemagglutinin per H3N2 vaccine strain, and 15 μg of haemagglutinin per B vaccine strain) (1) by microneedle patch or (2) by intramuscular injection, or received (3) placebo by microneedle patch, all administered by an unmasked health-care worker; or received a single dose of (4) inactivated influenza vaccine by microneedle patch self-administered by study participants. A research pharmacist prepared the randomisation code using a computer-generated randomisation schedule with a block size of 4. Because of the nature of the study, participants were not masked to the type of vaccination method (ie, microneedle patch vs intramuscular injection). Primary safety outcome measures are the incidence of study product-related serious adverse events within 180 days, grade 3 solicited or unsolicited adverse events within 28 days, and solicited injection site and systemic reactogenicity on the day of study product administration through 7 days after administration, and secondary safety outcomes are new-onset chronic illnesses within 180 days and unsolicited adverse events within 28 days, all analysed by intention to treat

  15. Effect of Influenza Vaccination of Children on Infection Rate in Hutterite Communities: Follow-Up Study of a Randomized Trial.

    Directory of Open Access Journals (Sweden)

    Biao Wang

    Full Text Available An earlier cluster randomized controlled trial (RCT of Hutterite colonies had shown that if more than 80% of children and adolescents were immunized with influenza vaccine there was a statistically significant reduction in laboratory-confirmed influenza among all unimmunized community members. We assessed the impact of this intervention for two additional influenza seasonal periods.Follow-up data for two influenza seasonal periods of a cluster randomized trial involving 1053 Canadian children and adolescents aged 36 months to 15 years in Season 2 and 1014 in Season 3 who received the study vaccine, and 2805 community members in Season 2 and 2840 in Season 3 who did not receive the study vaccine. Follow-up for Season 2 began November 18, 2009 and ended April 25, 2010 while Season 3 extended from December 6, 2010 and ended May 27, 2011. Children were randomly assigned in a blinded manner according to community membership to receive either inactivated trivalent influenza vaccine or hepatitis A. The primary outcome was confirmed influenza A and B infection using RT-PCR assay. Due to the outbreak of 2009 H1N1 pandemic, data in Season 2 were excluded for analysis.For an analysis of the combined Season 1 and Season 3 data, among non-recipients (i.e., participants who did not receive study vaccines, 66 of the 2794 (2.4% participants in the influenza vaccine colonies and 121 of the 2301 (5.3% participants in the hepatitis A colonies had influenza confirmed by RT-PCR, for a protective effectiveness of 60% (95% CI, 6% to 83%; P = 0.04; among all study participants (i.e., including both those who received study vaccine and those who did not, 125 of the 3806 (3.3% in the influenza vaccine colonies and 239 of the 3243 (7.4% in the hepatitis A colonies had influenza confirmed by RT-PCR, for a protective effectiveness of 63% (95% CI, 5% to 85%; P = 0.04.Immunizing children and adolescents with inactivated influenza vaccine can offer a protective effect among

  16. Frequency of apnea, bradycardia, and desaturations following first diphtheria-tetanus-pertussis-inactivated polio-Haemophilus influenzae type B immunization in hospitalized preterm infants.

    Science.gov (United States)

    Lee, Jackie; Robinson, Joan L; Spady, Donald W

    2006-06-19

    Adverse cardiorespiratory events including apnea, bradycardia, and desaturations have been described following administration of the first diphtheria-tetanus-pertussis-inactivated polio-Haemophilus influenzae type B (DTP-IPV-Hib) immunization to preterm infants. The effect of the recent substitution of acellular pertussis vaccine for whole cell pertussis vaccine on the frequency of these events requires further study. Infants with gestational age of apnea, bradycardia, and/or desaturations (ABD) and the treatment required for these episodes in the 72 hours prior to and 72 hours post-immunization (for the immunized cohort) or at the same post-natal age (for controls) was recorded. Thirty-four infants who received DTP-IPV-Hib with whole cell pertussis vaccine, 90 infants who received DTP-IPV-Hib with acellular pertussis vaccine, and 124 control infants were entered in the study. Fifty-six immunized infants (45.1%) and 36 control infants (29.0%) had a resurgence of or increased ABD in the 72 hours post-immunization in the immunized infants and at the same post-natal age in the controls with an adjusted odds ratio for immunized infants of 2.41 (95% CI 1.29,4.51) as compared to control infants. The incidence of an increase in adverse cardiorespiratory events post-immunization was the same in infants receiving whole cell or acellular pertussis vaccine (44.1% versus 45.6%). Eighteen immunized infants (14.5%) and 51 control infants (41.1%) had a reduction in ABD in the 72 hours post- immunization or at the equivalent postnatal age in controls for an odds ratio of 0.175 (95%CI 0.08, 0.39). The need for therapy of ABD in the immunized infants was not statistically different from the control infants. Lower weight at the time of immunization was a risk factor for a resurgence of or increased ABD post-immunization. Birth weight, gestational age, postnatal age or sex were not risk factors. There is an increase in adverse cardiorespiratory events following the first dose of DTP

  17. Induction of Heterosubtypic Cross-Protection against Influenza by a Whole Inactivated Virus Vaccine : The Role of Viral Membrane Fusion Activity

    NARCIS (Netherlands)

    Budimir, Natalija; Huckriede, Anke; Meijerhof, Tjarko; Boon, Louis; Gostick, Emma; Price, David A.; Wilschut, Jan; de Haan, Aalzen

    2012-01-01

    Background: The inability of seasonal influenza vaccines to effectively protect against infection with antigenically drifted viruses or newly emerging pandemic viruses underlines the need for development of cross-reactive influenza vaccines that induce immunity against a variety of virus subtypes.

  18. An Assessment of the Expected Cost-Effectiveness of Quadrivalent Influenza Vaccines in Ontario, Canada Using a Static Model.

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    Ayman Chit

    Full Text Available Ontario, Canada, immunizes against influenza using a trivalent inactivated influenza vaccine (IIV3 under a Universal Influenza Immunization Program (UIIP. The UIIP offers IIV3 free-of-charge to all Ontarians over 6 months of age. A newly approved quadrivalent inactivated influenza vaccine (IIV4 offers wider protection against influenza B disease. We explored the expected cost-utility and budget impact of replacing IIV3 with IIV4, within the context of Ontario's UIIP, using a probabilistic and static cost-utility model. Wherever possible, epidemiological and cost data were obtained from Ontario sources. Canadian or U.S. sources were used when Ontario data were not available. Vaccine efficacy for IIV3 was obtained from the literature. IIV4 efficacy was derived from meta-analysis of strain-specific vaccine efficacy. Conservatively, herd protection was not considered. In the base case, we used IIV3 and IIV4 prices of $5.5/dose and $7/dose, respectively. We conducted a sensitivity analysis on the price of IIV4, as well as standard univariate and multivariate statistical uncertainty analyses. Over a typical influenza season, relative to IIV3, IIV4 is expected to avert an additional 2,516 influenza cases, 1,683 influenza-associated medical visits, 27 influenza-associated hospitalizations, and 5 influenza-associated deaths. From a societal perspective, IIV4 would generate 76 more Quality Adjusted Life Years (QALYs and a net societal budget impact of $4,784,112. The incremental cost effectiveness ratio for this comparison was $63,773/QALY. IIV4 remains cost-effective up to a 53% price premium over IIV3. A probabilistic sensitivity analysis showed that IIV4 was cost-effective with a probability of 65% for a threshold of $100,000/QALY gained. IIV4 is expected to achieve reductions in influenza-related morbidity and mortality compared to IIV3. Despite not accounting for herd protection, IIV4 is still expected to be a cost-effective alternative to IIV3 up to

  19. Immunogenicity and Efficacy of A/H1N1pdm Vaccine Among Subjects With Severe Motor and Intellectual Disability in the 2010/11 Influenza Season

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    Megumi Hara

    2016-06-01

    Full Text Available Background: While the immunogenicity and effectiveness of seasonal influenza vaccines among subjects with severe motor and intellectual disability (SMID are known to be diminished, the efficacy of the A/H1N1pdm vaccine has not been evaluated. Methods: We prospectively evaluated 103 subjects with SMID (mean age, 41.7 years who received trivalent inactivated influenza vaccine during the 2010/11 influenza season. The hemagglutination inhibition (HI antibody titer was measured in serum samples collected pre-vaccination (S0, post-vaccination (S1, and end-of-season (S2 to evaluate subjects’ immunogenicity capacity. Vaccine efficacy was assessed based on antibody efficacy and achievement proportion. Results: The proportions of seroprotection and seroconversion, and the geometric mean titer (GMT ratio (GMT at S1/GMT at S0 for A/H1N1pdm were 46.0%, 16.0%, and 1.8, respectively—values which did not meet the European Medicines Evaluation Agency criteria. The achievement proportion was 26%. During follow-up, 11 of 43 subjects with acute respiratory illness were diagnosed with type A influenza according to a rapid influenza diagnostic test (RIDT, and A/H1N1pdm strains were isolated from the throat swabs of 5 of those 11 subjects. When either or both RIDT-diagnosed influenza or serologically diagnosed influenza (HI titer at S2/HI titer at S1 ≥2 were defined as probable influenza, subjects with A/H1N1pdm seroprotection were found to have a lower incidence of probable influenza (odds ratio, 0.31; antibody efficacy, 69%; vaccine efficacy, 18%. Conclusions: In the present seasonal assessment, antibody efficacy was moderate against A/H1N1pdm among SMID subjects, but vaccine efficacy was low due to the reduced immunogenicity of SMID subjects.

  20. Efficacy of single dose of a bivalent vaccine containing inactivated Newcastle disease virus and reassortant highly pathogenic avian influenza H5N1 virus against lethal HPAI and NDV infection in chickens.

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    Dong-Hun Lee

    Full Text Available Highly pathogenic avian influenza (HPAI and Newcastle disease (ND are 2 devastating diseases of poultry, which cause great economic losses to the poultry industry. In the present study, we developed a bivalent vaccine containing antigens of inactivated ND and reassortant HPAI H5N1 viruses as a candidate poultry vaccine, and we evaluated its immunogenicity and protective efficacy in specific pathogen-free chickens. The 6:2 reassortant H5N1 vaccine strain containing the surface genes of the A/Chicken/Korea/ES/2003(H5N1 virus was successfully generated by reverse genetics. A polybasic cleavage site of the hemagglutinin segment was replaced by a monobasic cleavage site. We characterized the reverse genetics-derived reassortant HPAI H5N1 clade 2.5 vaccine strain by evaluating its growth kinetics in eggs, minimum effective dose in chickens, and cross-clade immunogenicity against HPAI clade 1 and 2. The bivalent vaccine was prepared by emulsifying inactivated ND (La Sota strain and reassortant HPAI viruses with Montanide ISA 70 adjuvant. A single immunization with this vaccine induced high levels of hemagglutination-inhibiting antibody titers and protected chickens against a lethal challenge with the wild-type HPAI and ND viruses. Our results demonstrate that the bivalent, inactivated vaccine developed in this study is a promising approach for the control of both HPAI H5N1 and ND viral infections.

  1. Influenza Vaccine Effectiveness in Preventing Influenza Illness Among Children During School-based Outbreaks in the 2014-2015 Season in Beijing, China.

    Science.gov (United States)

    Zhang, Li; Yang, Peng; Thompson, Mark G; Pan, Yang; Ma, Chunna; Wu, Shuangsheng; Sun, Ying; Zhang, Man; Duan, Wei; Wang, Quanyi

    2017-03-01

    Little is known about vaccine effectiveness (VE) against nonmedically attended A(H3N2) influenza illness during 2014-2015 when the vaccine component appeared to be a poor match with circulating strains. Forty-three eligible school influenza outbreaks in Beijing, China, from November 1, 2014, to December 31, 2014, were included in this study. The VE of 2014-2015 trivalent inactivated influenza vaccine (IIV3) was assessed in preventing laboratory-confirmed influenza among school-age children through a case-control design, using asymptomatic controls. Influenza vaccination was documented from a vaccination registry. VE was estimated adjusting for age group, sex, rural versus urban area, body mass index, chronic conditions, onset week and schools through a mixed effects logistic regression model. The average coverage rate of 2014-2015 IIV3 among students across the 43 schools was 47.6%. The fully adjusted VE of 2014-2015 IIV3 against laboratory-confirmed influenza was 38% [95% confidence interval (CI): 12%-57%]. Receipt of previous season's (2013-2014) IIV3 significantly modified VE of the 2014-2015 IIV3; children who received both 2013-2014 and 2014-2015 vaccinations had VE of 29% (95% CI: -8% to 53%), whereas VE for children who received 2014-2015 IIV3 only was 54% (95% CI: 8%-77%). VE for 2014-2015 IIV3 against A(H3N2) illness identified in schools was modest. Children who did not receive the prior season's vaccine with a homologous A(H3N2) component may have enjoyed greater protection than repeated vaccinees.

  2. Retrospective public health impact of a quadrivalent influenza vaccine in the United States

    NARCIS (Netherlands)

    Crepey, Pascal; de Boer, Pieter T.; Postma, Maarten J.; Pitman, Richard

    IntroductionVaccination is an effective preventive strategy against influenza. However, current trivalent influenza vaccines (TIVs) contain only one of the two influenza B lineages that circulate each year. Vaccine mismatches are frequent because predicting which one will predominate is difficult.

  3. Influenza pandemic (H1N1 2009 activity during summer 2009: Effectiveness of the 2008-9 trivalent vaccine against pandemic influenza in Spain Actividad de la gripe pandémica (H1N1 2009 durante el verano de 2009: Efectividad de la vacuna trivalente 2008-9 frente a la gripe pandémica en España

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    Amparo Larrauri

    2011-02-01

    Full Text Available Introduction: The Spanish influenza surveillance system (SISS maintained its activity during the summer of 2009 to monitor the influenza pandemic. Objectives: To describe pandemic influenza activity from May to September 2009 and to estimate the effectiveness of the 2008-9 seasonal influenza vaccine against laboratory-confirmed pandemic (H1N1 2009 influenza. Methods: Data from the SISS were used to identify the trend of pandemic (H1N1 2009 influenza outside the influenza season. For the effectiveness study, we compared the vaccination status of notified cases [influenza-like illnesses (ILI laboratory confirmed as pandemic influenza] with that of the test-negative controls. Results: The first laboratory-confirmed case of the pandemic virus was notified in the system in week 20/2009. The ILI rate increased gradually in the study period, exceeding basic activity in week 38. The proportion of pandemic (H1N1 2009 influenza viruses detected by the system represented 14% in week 20/2009 and rapidly increased to 90% in week 34. The adjusted vaccine effectiveness of the 2008-9 seasonal vaccine against laboratory-confirmed pandemic influenza was 12% (-30; 41. Conclusions: The SISS became an essential tool for pandemic monitoring in Spain. The improved SISS will provide more accurate information on influenza activity in future seasonal or pandemic waves. Using surveillance data, we could not demonstrate the effectiveness of the seasonal 2008-9 vaccine against laboratory-confirmed pandemic influenza.Introducción: El Sistema de Vigilancia de Gripe en España (SVGE continuó y reforzó su actividad durante el verano de 2009 con el objetivo de vigilar la evolución de la pandemia en España. Objetivos: Describir la actividad de la gripe pandémica en España de mayo a septiembre de 2009 y estimar la efectividad de la vacuna antigripal estacional 2008-2009 frente a casos confirmados de gripe pandémica (H1N1 2009. Métodos: Se utilizaron datos del SVGE para

  4. Frequency of apnea, bradycardia, and desaturations following first diphtheria-tetanus-pertussis-inactivated polio-Haemophilus influenzae type B immunization in hospitalized preterm infants

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    Spady Donald W

    2006-06-01

    Full Text Available Abstract Background Adverse cardiorespiratory events including apnea, bradycardia, and desaturations have been described following administration of the first diphtheria-tetanus-pertussis-inactivated polio-Haemophilus influenzae type B (DTP-IPV-Hib immunization to preterm infants. The effect of the recent substitution of acellular pertussis vaccine for whole cell pertussis vaccine on the frequency of these events requires further study. Methods Infants with gestational age of ≤ 32 weeks who received their first DTP-IPV-Hib immunization prior to discharge from two Edmonton Neonatal Intensive Care Units January 1, 1996 to November 30, 2000 were eligible for the study. Each immunized infant was matched by gestational age to one control infant. The number of episodes of apnea, bradycardia, and/or desaturations (ABD and the treatment required for these episodes in the 72 hours prior to and 72 hours post-immunization (for the immunized cohort or at the same post-natal age (for controls was recorded. Results Thirty-four infants who received DTP-IPV-Hib with whole cell pertussis vaccine, 90 infants who received DTP-IPV-Hib with acellular pertussis vaccine, and 124 control infants were entered in the study. Fifty-six immunized infants (45.1% and 36 control infants (29.0% had a resurgence of or increased ABD in the 72 hours post-immunization in the immunized infants and at the same post-natal age in the controls with an adjusted odds ratio for immunized infants of 2.41 (95% CI 1.29,4.51 as compared to control infants. The incidence of an increase in adverse cardiorespiratory events post-immunization was the same in infants receiving whole cell or acellular pertussis vaccine (44.1% versus 45.6%. Eighteen immunized infants (14.5% and 51 control infants (41.1% had a reduction in ABD in the 72 hours post- immunization or at the equivalent postnatal age in controls for an odds ratio of 0.175 (95%CI 0.08, 0.39. The need for therapy of ABD in the immunized

  5. Evaluation of in vitro cross-reactivity to avian H5N1 and pandemic H1N1 2009 influenza following prime boost regimens of seasonal influenza vaccination in healthy human subjects: a randomised trial.

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    Delia Bethell

    Full Text Available INTRODUCTION: Recent studies have demonstrated that inactivated seasonal influenza vaccines (IIV may elicit production of heterosubtypic antibodies, which can neutralize avian H5N1 virus in a small proportion of subjects. We hypothesized that prime boost regimens of live and inactivated trivalent seasonal influenza vaccines (LAIV and IIV would enhance production of heterosubtypic immunity and provide evidence of cross-protection against other influenza viruses. METHODS: In an open-label study, 26 adult volunteers were randomized to receive one of four vaccine regimens containing two doses of 2009-10 seasonal influenza vaccines administered 8 (±1 weeks apart: 2 doses of LAIV; 2 doses of IIV; LAIV then IIV; IIV then LAIV. Humoral immunity assays for avian H5N1, 2009 pandemic H1N1 (pH1N1, and seasonal vaccine strains were performed on blood collected pre-vaccine and 2 and 4 weeks later. The percentage of cytokine-producing T-cells was compared with baseline 14 days after each dose. RESULTS: Subjects receiving IIV had prompt serological responses to vaccine strains. Two subjects receiving heterologous prime boost regimens had enhanced haemagglutination inhibition (HI and neutralization (NT titres against pH1N1, and one subject against avian H5N1; all three had pre-existing cross-reactive antibodies detected at baseline. Significantly elevated titres to H5N1 and pH1N1 by neuraminidase inhibition (NI assay were observed following LAIV-IIV administration. Both vaccines elicited cross-reactive CD4+ T-cell responses to nucleoprotein of avian H5N1 and pH1N1. All regimens were safe and well tolerated. CONCLUSION: Neither homologous nor heterologous prime boost immunization enhanced serum HI and NT titres to 2009 pH1N1 or avian H5N1 compared to single dose vaccine. However heterologous prime-boost vaccination did lead to in vitro evidence of cross-reactivity by NI; the significance of this finding is unclear. These data support the strategy of

  6. The Cost-Effectiveness and Value of Information of Three Influenza Vaccination Dosing Strategies for Individuals with Human Immunodeficiency Virus

    Science.gov (United States)

    Nosyk, Bohdan; Sharif, Behnam; Sun, Huiying; Cooper, Curtis; Anis, Aslam H.

    2011-01-01

    Background Influenza vaccine immunogenicity is diminished in patients living with HIV/AIDS. We evaluated the cost-effectiveness and expected value of perfect information (EVPI) of three alternative influenza vaccine dosing strategies intended to increase immunogenicity in those patients. Methods A randomized, multi-centered, controlled, vaccine trial was conducted at 12 CIHR Canadian HIV Trials Network sites. Three dosing strategies with seasonal, inactivated trivalent, non-adjuvanted intramuscular vaccine were used in HIV infected adults: two standard doses over 28 days (Strategy A), two double doses over 28 days (Strategy B) and a single standard dose of influenza vaccine (Strategy C), administered prior to the 2008 influenza season. The comparator in our analysis was practice in the previous year, in which 82.8% of HIV/AIDS received standard-dose vaccination (Strategy D). A Markov cohort model was developed to estimate the monthly probability of Influenza-like Illness (ILI) over one influenza season. Costs and quality-adjusted life years, extrapolated to the lifetime of the hypothetical study cohorts, were estimated in calculating incremental cost-effectiveness ratios (ICER) and EVPI in conducting further research. Results 298 patients with median CD4 of 470 cells/µl and 76% with viral load suppression were randomized. Strategy C was the most cost-effective strategy for the overall trial population and for suppressed and unsuppressed individuals. Mean ICERs for Strategy A for unsuppressed patients could also be considered cost-effective. The level of uncertainty regarding the decision to implement strategy A versus C for unsuppressed individuals was high. The maximum acceptable cost of reducing decision uncertainty in implementing strategy A for individuals with unsuppressed pVL was $418,000 - below the cost of conducting a larger-scale trial. Conclusion Our results do not support a policy to implement increased antigen dose or booster dosing strategies with

  7. [Universal immunisation against influenza in paediatrics, yes or no?].

    Science.gov (United States)

    González de Dios, J; Rodrigo Gonzalo de Liria, C; Piedra, P A; Corretger Rauet, J M; Moreno-Pérez, D

    2013-10-01

    The recommendations on influenza vaccination are not homogeneous between countries, with striking differences between the current recommendations in United States and Europe. The objective of the study is to determine the efficacy, effectiveness and safety of the current flu vaccine (trivalent inactivated vaccine and adapted to the cold [LAIV] live virus vaccine) in healthy children, and to try and answer the following question: universal immunization against influenza in Paediatrics, yes or no? A scheme of work based on the five standard steps of evidence or science-based medicine was used: 1) question, 2) search, 3) valuation, 4) applicability and 5) adequacy. Nine systematic reviews, published between 2005 and 2012, were selected that answered our clinical question, and which included the best available information (randomised clinical trials, cohort studies and case studies). The flu vaccine in childhood has the right cost - benefit - risk relationship. In all systematic reviews the efficacy of the flu vaccine varied between 58%-65%, and effectiveness between 28%-61%. Both efficacy and effectiveness increase with age, and there are limited studies showing sufficient evidence in children < 2 years. There are further areas to develop: more and better clinical trials on influenza vaccines in infants from 6 to 23 months; further research to achieve better influenza vaccines (addition of adjuvants, higher doses in children between 6 and 23 months, and study the LAIV vaccine in children between 6 and 23 months); and improvement in the prediction of vaccine strains responsible for the outbreak. Copyright © 2012 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  8. Inactivation of the Thymidylate Synthase thyA in Non-typeable Haemophilus influenzae Modulates Antibiotic Resistance and Has a Strong Impact on Its Interplay with the Host Airways.

    Science.gov (United States)

    Rodríguez-Arce, Irene; Martí, Sara; Euba, Begoña; Fernández-Calvet, Ariadna; Moleres, Javier; López-López, Nahikari; Barberán, Montserrat; Ramos-Vivas, José; Tubau, Fe; Losa, Carmen; Ardanuy, Carmen; Leiva, José; Yuste, José E; Garmendia, Junkal

    2017-01-01

    Antibacterial treatment with cotrimoxazol (TxS), a combination of trimethoprim and sulfamethoxazole, generates resistance by, among others, acquisition of thymidine auxotrophy associated with mutations in the thymidylate synthase gene thyA , which can modify the biology of infection. The opportunistic pathogen non-typeable Haemophilus influenzae (NTHi) is frequently encountered in the lower airways of chronic obstructive pulmonary disease (COPD) patients, and associated with acute exacerbation of COPD symptoms. Increasing resistance of NTHi to TxS limits its suitability as initial antibacterial against COPD exacerbation, although its relationship with thymidine auxotrophy is unknown. In this study, the analysis of 2,542 NTHi isolates recovered at Bellvitge University Hospital (Spain) in the period 2010-2014 revealed 119 strains forming slow-growing colonies on the thymidine low concentration medium Mueller Hinton Fastidious, including one strain isolated from a COPD patient undergoing TxS therapy that was a reversible thymidine auxotroph. To assess the impact of thymidine auxotrophy in the NTHi-host interplay during respiratory infection, thyA mutants were generated in both the clinical isolate NTHi375 and the reference strain RdKW20. Inactivation of the thyA gene increased TxS resistance, but also promoted morphological changes consistent with elongation and impaired bacterial division, which altered H. influenzae self-aggregation, phosphorylcholine level, C3b deposition, and airway epithelial infection patterns. Availability of external thymidine contributed to overcome such auxotrophy and TxS effect, potentially facilitated by the nucleoside transporter nupC . Although, thyA inactivation resulted in bacterial attenuation in a lung infection mouse model, it also rendered a lower clearance upon a TxS challenge in vivo . Thus, our results show that thymidine auxotrophy modulates both the NTHi host airway interplay and antibiotic resistance, which should be

  9. A Systematic Review of Safety and Immunogenicity of Influenza Vaccination Strategies in Solid Organ Transplant Recipients.

    Science.gov (United States)

    Chong, Pearlie P; Handler, Lara; Weber, David J

    2017-12-14

    Immunogenicity from seasonal inactivated influenza vaccine (IIV) remains suboptimal in solid organ transplant recipients (SOTR). We conducted a systematic review that compared the safety and immunogenicity of non-standard influenza vaccination strategies to single dose IIV in SOTR. Booster dose(s) and possibly high dose (HD) influenza vaccination strategies appear to hold promise for improving vaccination immunogenicity in SOTR. Administration of intradermal and MF59-adjuvanted trivalent IIV (IIV3) did not improve vaccine immunogenicity compared to single dose intramuscular IIV. Alternative vaccine strategies were generally well-tolerated; a higher frequency of injection site reactions and systemic adverse events were noted in SOTR who received HD, intradermal or adjuvanted IIV3 and HD IIV3 respectively. Allograft rejection rates were similar in both groups. SOTR should continue to receive standard dose IIV annually in accordance to current recommendations pending future studies to determine the optimal timing, frequency and dose(s) of IIV using the booster dose strategy. © The Author(s) 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  10. Vaccination with adjuvanted recombinant neuraminidase induces broad heterologous, but not heterosubtypic, cross-protection against influenza virus infection in mice.

    Science.gov (United States)

    Wohlbold, Teddy John; Nachbagauer, Raffael; Xu, Haoming; Tan, Gene S; Hirsh, Ariana; Brokstad, Karl A; Cox, Rebecca J; Palese, Peter; Krammer, Florian

    2015-03-10

    In an attempt to assess the cross-protective potential of the influenza virus neuraminidase (NA) as a vaccine antigen, different subtypes of recombinant NA were expressed in a baculovirus system and used to vaccinate mice prior to lethal challenge with homologous, heterologous, or heterosubtypic viruses. Mice immunized with NA of subtype N2 were completely protected from morbidity and mortality in a homologous challenge and displayed significantly reduced viral lung titers. Heterologous challenge with a drifted strain resulted in morbidity but no mortality. Similar results were obtained for challenge experiments with N1 NA. Mice immunized with influenza B virus NA (from B/Yamagata/16/88) displayed no morbidity when sublethally infected with the homologous strain and, importantly, were completely protected from morbidity and mortality when lethally challenged with the prototype Victoria lineage strain or a more recent Victoria lineage isolate. Upon analyzing the NA content in 4 different inactivated-virus vaccine formulations from the 2013-2014 season via Western blot assay and enzyme-linked immunosorbent assay quantification, we found that the amount of NA does indeed vary across vaccine brands. We also measured hemagglutinin (HA) and NA endpoint titers in pre- and postvaccination human serum samples from individuals who received a trivalent inactivated seasonal influenza vaccine from the 2004-2005 season; the induction of NA titers was statistically less pronounced than the induction of HA titers. The demonstrated homologous and heterologous protective capacity of recombinant NA suggests that supplementing vaccine formulations with a standard amount of NA may offer increased protection against influenza virus infection. Despite the existence of vaccine prophylaxis and antiviral therapeutics, the influenza virus continues to cause morbidity and mortality in the human population, emphasizing the continued need for research in the field. While the majority of

  11. Seasonal influenza vaccination for children in Thailand: a cost-effectiveness analysis.

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    Aronrag Meeyai

    2015-05-01

    Full Text Available Seasonal influenza is a major cause of mortality worldwide. Routine immunization of children has the potential to reduce this mortality through both direct and indirect protection, but has not been adopted by any low- or middle-income countries. We developed a framework to evaluate the cost-effectiveness of influenza vaccination policies in developing countries and used it to consider annual vaccination of school- and preschool-aged children with either trivalent inactivated influenza vaccine (TIV or trivalent live-attenuated influenza vaccine (LAIV in Thailand. We also compared these approaches with a policy of expanding TIV coverage in the elderly.We developed an age-structured model to evaluate the cost-effectiveness of eight vaccination policies parameterized using country-level data from Thailand. For policies using LAIV, we considered five different age groups of children to vaccinate. We adopted a Bayesian evidence-synthesis framework, expressing uncertainty in parameters through probability distributions derived by fitting the model to prospectively collected laboratory-confirmed influenza data from 2005-2009, by meta-analysis of clinical trial data, and by using prior probability distributions derived from literature review and elicitation of expert opinion. We performed sensitivity analyses using alternative assumptions about prior immunity, contact patterns between age groups, the proportion of infections that are symptomatic, cost per unit vaccine, and vaccine effectiveness. Vaccination of children with LAIV was found to be highly cost-effective, with incremental cost-effectiveness ratios between about 2,000 and 5,000 international dollars per disability-adjusted life year averted, and was consistently preferred to TIV-based policies. These findings were robust to extensive sensitivity analyses. The optimal age group to vaccinate with LAIV, however, was sensitive both to the willingness to pay for health benefits and to assumptions

  12. Thermal inactivation of H5N2 high pathogenicity avian influenza virus in dried egg white with 7.5% moisture

    Science.gov (United States)

    High pathogenicity avian influenza viruses (HPAIV) cause severe systemic disease with high mortality in chickens. Isolation of HPAIV from the internal contents of chicken eggs has been reported, and this is cause for concern because HPAIV can be spread by movement of poultry products during marketi...

  13. Evaluation of homologous inactivated influenza vaccine for protection of chickens against the H7N9 virus isolated in Anhui, China during 2013

    Science.gov (United States)

    The recent outbreak of avian influenza (AI) H7N9 in humans in China in 2013 has resulted in approximately 30 % mortality. The genetic composition of these H7N9 viruses appears to be solely of avian origin. Although few isolations of these viruses have been demonstrated on poultry farms, the correlat...

  14. Pulmonary immunization of chickens using non-adjuvanted spray-freeze dried whole inactivated virus vaccine completely protects against highly pathogenic H5N1 avian influenza virus.

    NARCIS (Netherlands)

    Peeters, B.P.H.; Tonnis, W.F.; Murugappan, S.; Rottier, P.; Koch, G.; Frijlink, H.W.; Huckriede, A.; Hinrichs, W.L.J.

    2014-01-01

    Highly pathogenic avian influenza (HPAI) H5N1 virus is a major threat to public health as well as to the global poultry industry. Most fatal human infections are caused by contact with infected poultry. Therefore, preventing the virus from entering the poultry population is a priority. This is,

  15. Initial Identification and Characterization of an Emerging Zoonotic Influenza Prior to Pandemic Spread

    Science.gov (United States)

    2010-11-01

    H3). These two samples became the first reported cases of the pandemic 2009/ H1N1 influenza virus . The first reportable characterization was made...identified as “untypeable” influenza A virus . In the case of the 28 March sample, this diagnosis was made using an in-house accredited (homebrew...as well as reassortment. TABLE 2. Primer pair detection for 2009 pandemic H1N1 influenza virus and FluMist trivalent influenza vaccine and base

  16. Cost-effectiveness and public health impact of alternative influenza vaccination strategies in high-risk adults.

    Science.gov (United States)

    Raviotta, Jonathan M; Smith, Kenneth J; DePasse, Jay; Brown, Shawn T; Shim, Eunha; Nowalk, Mary Patricia; Wateska, Angela; France, Glenson S; Zimmerman, Richard K

    2017-10-09

    High-dose trivalent inactivated influenza vaccine (HD-IIV3) or recombinant trivalent influenza vaccine (RIV) may increase influenza vaccine effectiveness (VE) in adults with conditions that place them at high risk for influenza complications. This analysis models the public health impact and cost-effectiveness (CE) of these vaccines for 50-64year-olds. Markov model CE analysis compared 5 strategies in 50-64year-olds: no vaccination; only standard-dose IIV3 offered (SD-IIV3 only), only quadrivalent influenza vaccine offered (SD-IIV4 only); high-risk patients receiving HD-IIV3, others receiving SD-IIV3 (HD-IIV3 & SD-IIV3); and high-risk patients receiving HD-IIV3, others receiving SD-IIV4 (HD-IIV3 & SD-IIV4). In a secondary analysis, RIV replaced HD-IIV3. Parameters were obtained from U.S. databases, the medical literature and extrapolations from VE estimates. Effectiveness was measured as 3%/year discounted quality adjusted life year (QALY) losses avoided. The least expensive strategy was SD-IIV3 only, with total costs of $99.84/person. The SD-IIV4 only strategy cost an additional $0.91/person, or $37,700/QALY gained. The HD-IIV3 & SD-IIV4 strategy cost $1.06 more than SD-IIV4 only, or $71,500/QALY gained. No vaccination and HD-IIV3 & SD-IIV3 strategies were dominated. Results were sensitive to influenza incidence, vaccine cost, standard-dose VE in the entire population and high-dose VE in high-risk patients. The CE of RIV for high-risk patients was dependent on as yet unknown parameter values. Based on available data, using high-dose influenza vaccine or RIV in middle-aged, high-risk patients may be an economically favorable vaccination strategy with public health benefits. Clinical trials of these vaccines in this population may be warranted. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Influenza-specific T cells from older people are enriched in the late effector subset and their presence inversely correlates with vaccine response.

    Science.gov (United States)

    Wagar, Lisa E; Gentleman, Beth; Pircher, Hanspeter; McElhaney, Janet E; Watts, Tania H

    2011-01-01

    T cells specific for persistent pathogens accumulate with age and express markers of immune senescence. In contrast, much less is known about the state of T cell memory for acutely infecting pathogens. Here we examined T cell responses to influenza in human peripheral blood mononuclear cells from older (>64) and younger (<40) donors using whole virus restimulation with influenza A (A/PR8/34) ex vivo. Although most donors had pre-existing influenza reactive T cells as measured by IFNγ production, older donors had smaller populations of influenza-responsive T cells than young controls and had lost a significant proportion of their CD45RA-negative functional memory population. Despite this apparent dysfunction in a proportion of the older T cells, both old and young donors' T cells from 2008 could respond to A/California/07/2009 ex vivo. For HLA-A2+ donors, MHC tetramer staining showed that a higher proportion of influenza-specific memory CD8 T cells from the 65+ group co-express the markers killer cell lectin-like receptor G1 (KLRG1) and CD57 compared to their younger counterparts. These markers have previously been associated with a late differentiation state or immune senescence. Thus, memory CD8 T cells to an acutely infecting pathogen show signs of advanced differentiation and functional deterioration with age. There was a significant negative correlation between the frequency of KLRG1(+)CD57(+) influenza M1-specific CD8 T cells pre-vaccination and the ability to make antibodies in response to vaccination with seasonal trivalent inactivated vaccine, whereas no such trend was observed when the total CD8(+)KLRG1(+)CD57(+) population was analyzed. These results suggest that the state of the influenza-specific memory CD8 T cells may be a predictive indicator of a vaccine responsive healthy immune system in old age.

  18. Influenza-specific T cells from older people are enriched in the late effector subset and their presence inversely correlates with vaccine response.

    Directory of Open Access Journals (Sweden)

    Lisa E Wagar

    Full Text Available T cells specific for persistent pathogens accumulate with age and express markers of immune senescence. In contrast, much less is known about the state of T cell memory for acutely infecting pathogens. Here we examined T cell responses to influenza in human peripheral blood mononuclear cells from older (>64 and younger (<40 donors using whole virus restimulation with influenza A (A/PR8/34 ex vivo. Although most donors had pre-existing influenza reactive T cells as measured by IFNγ production, older donors had smaller populations of influenza-responsive T cells than young controls and had lost a significant proportion of their CD45RA-negative functional memory population. Despite this apparent dysfunction in a proportion of the older T cells, both old and young donors' T cells from 2008 could respond to A/California/07/2009 ex vivo. For HLA-A2+ donors, MHC tetramer staining showed that a higher proportion of influenza-specific memory CD8 T cells from the 65+ group co-express the markers killer cell lectin-like receptor G1 (KLRG1 and CD57 compared to their younger counterparts. These markers have previously been associated with a late differentiation state or immune senescence. Thus, memory CD8 T cells to an acutely infecting pathogen show signs of advanced differentiation and functional deterioration with age. There was a significant negative correlation between the frequency of KLRG1(+CD57(+ influenza M1-specific CD8 T cells pre-vaccination and the ability to make antibodies in response to vaccination with seasonal trivalent inactivated vaccine, whereas no such trend was observed when the total CD8(+KLRG1(+CD57(+ population was analyzed. These results suggest that the state of the influenza-specific memory CD8 T cells may be a predictive indicator of a vaccine responsive healthy immune system in old age.

  19. Inactivated influenza vaccine adjuvanted with Bacterium-like particles induce systemic and mucosal influenza A virus specific T-cell and B-cell responses after nasal administration in a TLR2 dependent fashion

    NARCIS (Netherlands)

    Keijzer, C.; Haijema, B. J.; Meijerhof, T.; Voorn, P.; de Haan, A.; Leenhouts, K.; van Roosmalen, M. L.; van Eden, W.; Broere, F.

    2014-01-01

    Background: Nasal vaccination is considered to be a promising alternative for parenteral vaccination against influenza virus as it is non-invasive and offers the opportunity to elicit strong antigen-specific responses both systemic and locally at the port of entry of the pathogen. Previous studies

  20. Vaccination with Adjuvanted Recombinant Neuraminidase Induces Broad Heterologous, but Not Heterosubtypic, Cross-Protection against Influenza Virus Infection in Mice

    Science.gov (United States)

    Wohlbold, Teddy John; Nachbagauer, Raffael; Xu, Haoming; Tan, Gene S.; Hirsh, Ariana; Brokstad, Karl A.; Cox, Rebecca J.; Palese, Peter

    2015-01-01

    ABSTRACT In an attempt to assess the cross-protective potential of the influenza virus neuraminidase (NA) as a vaccine antigen, different subtypes of recombinant NA were expressed in a baculovirus system and used to vaccinate mice prior to lethal challenge with homologous, heterologous, or heterosubtypic viruses. Mice immunized with NA of subtype N2 were completely protected from morbidity and mortality in a homologous challenge and displayed significantly reduced viral lung titers. Heterologous challenge with a drifted strain resulted in morbidity but no mortality. Similar results were obtained for challenge experiments with N1 NA. Mice immunized with influenza B virus NA (from B/Yamagata/16/88) displayed no morbidity when sublethally infected with the homologous strain and, importantly, were completely protected from morbidity and mortality when lethally challenged with the prototype Victoria lineage strain or a more recent Victoria lineage isolate. Upon analyzing the NA content in 4 different inactivated-virus vaccine formulations from the 2013-2014 season via Western blot assay and enzyme-linked immunosorbent assay quantification, we found that the amount of NA does indeed vary across vaccine brands. We also measured hemagglutinin (HA) and NA endpoint titers in pre- and postvaccination human serum samples from individuals who received a trivalent inactivated seasonal influenza vaccine from the 2004-2005 season; the induction of NA titers was statistically less pronounced than the induction of HA titers. The demonstrated homologous and heterologous protective capacity of recombinant NA suggests that supplementing vaccine formulations with a standard amount of NA may offer increased protection against influenza virus infection. PMID:25759506

  1. Current strategic thinking for the development of a trivalent alphavirus vaccine for human use.

    Science.gov (United States)

    Wolfe, Daniel N; Heppner, D Gray; Gardner, Shea N; Jaing, Crystal; Dupuy, Lesley C; Schmaljohn, Connie S; Carlton, Kevin

    2014-09-01

    Vaccinations against the encephalitic alphaviruses (western, eastern, and Venezuelan equine encephalitis virus) are of significant interest to biological defense, public health, and agricultural communities alike. Although vaccines licensed for veterinary applications are used in the Western Hemisphere and attenuated or inactivated viruses have been used under Investigational New Drug status to protect at-risk personnel, there are currently no licensed vaccines for use in humans. Here, we will discuss the need for a trivalent vaccine that can protect humans against all three viruses, recent progress to such a vaccine, and a strategy to continue development to Food and Drug Administration licensure. © The American Society of Tropical Medicine and Hygiene.

  2. Separation method of trivalent actinide and rare earth element

    International Nuclear Information System (INIS)

    Koma, Yoshikazu; Watabe, Masayuki; Nemoto, Shin-ichi.

    1997-01-01

    Trivalent actinides and rare earth elements are extracted to a solvent from highly acidic liquid wastes generated upon reprocessing of spent fuels. The concentration of nitric acid in the extracted solvent is reduced. Trivalent actinides and the rare earth elements contained in the solvent at low nitric acid concentration are separated from each other. Trivalent actinides and rare earth elements are extracted into a highly acidic solvent in the extracting step of trivalent actinides and rare earth elements. On the other hand, they can be separated by extraction only at a predetermined pH in the separation step of the rare earth elements and trivalent actinides. In the present invention, trivalent actinides and rare earth elements are separated after removing a predetermined amount of nitric acid from the solution obtained in the trivalent actinide and rare earth element extraction step to provide a proper acidic concentration. Accordingly, they can be separated satisfactorily. (T.M.)

  3. Cross-lineage influenza B and heterologous influenza A antibody responses in vaccinated mice: immunologic interactions and B/Yamagata dominance.

    Directory of Open Access Journals (Sweden)

    Danuta M Skowronski

    Full Text Available The annually reformulated trivalent inactivated influenza vaccine (TIV includes both influenza A/subtypes (H3N2 and H1N1 but only one of two influenza B/lineages (Yamagata or Victoria. In a recent series of clinical trials to evaluate prime-boost response across influenza B/lineages, influenza-naïve infants and toddlers originally primed with two doses of 2008-09 B/Yamagata-containing TIV were assessed after two doses of B/Victoria-containing TIV administered in the subsequent 2009-10 and 2010-11 seasons. In these children, the Victoria-containing vaccines strongly recalled antibody to the initiating B/Yamagata antigen but induced only low B/Victoria antibody responses. To further evaluate this unexpected pattern of cross-lineage vaccine responses, we conducted additional immunogenicity assessment in mice. In the current study, mice were primed with two doses of 2008-09 Yamagata-containing TIV and subsequently boosted with two doses of 2010-11 Victoria-containing TIV (Group-Yam/Vic. With the same vaccines, we also assessed the reverse order of two-dose Victoria followed by two-dose Yamagata immunization (Group-Vic/Yam. The Group-Yam/Vic mice showed strong homologous responses to Yamagata antigen. However, as previously reported in children, subsequent doses of Victoria antigen substantially boosted Yamagata but induced only low antibody response to the immunizing Victoria component. The reverse order of Group-Vic/Yam mice also showed low homologous responses to Victoria but subsequent heterologous immunization with even a single dose of Yamagata antigen induced substantial boost response to both lineages. For influenza A/H3N2, homologous responses were comparably robust for the differing TIV variants and even a single follow-up dose of the heterologous strain, regardless of vaccine sequence, substantially boosted antibody to both strains. For H1N1, two doses of 2008-09 seasonal antigen significantly blunted response to two doses of the 2010

  4. In contrast to conventional inactivated influenza vaccines, 4xM2e.HSP70c fusion protein fully protected mice against lethal dose of H1, H3 and H9 influenza A isolates circulating in Iran

    International Nuclear Information System (INIS)

    Ebrahimi, Seyyed Mahmoud; Dabaghian, Mehran; Tebianian, Majid; Zabeh Jazi, Mohammad Hossein

    2012-01-01

    Ideal vaccines against influenza viruses should elicit not only a humoral response, but also a cellular response. Mycobacterium tuberculosis HSP70 (mHSP70) have been found to promote immunogenic APCs function, elicit a strong cytotoxic T lymphocyte (CTL) response, and prevent the induction of tolerance. Moreover, it showed linkage of antigens to the C-terminus of mHSP70 (mHSP70c) can represent them as vaccines resulted in more potent, protective antigen specific responses in the absence of adjuvants or complex formulations. Hence, recombinant fusion protein comprising C-terminus of mHSP70 genetically fused to four tandem repeats of the ectodomain of the conserved influenza matrix protein M2 (M2e) was expressed in Escherichia coli, purified under denaturing condition, refolding, and then confirmed by SDS–PAGE, respectively. The recombinant fusion protein, 4xM2e.HSP70c, retained its immunogenicity and displayed the protective epitope of M2e by ELISA and FITC assays. A prime-boost administration of 4xM2e.HSP70c formulated in F105 buffer by intramuscular route in mice (Balb/C) provided full protection against lethal dose of mouse-adapted H1N1, H3N2, or H9N2 influenza A isolates from Iran compared to 0–33.34% survival rate of challenged unimmunized and immunized mice with the currently in use conventional vaccines designated as control groups. However, protection induced by immunization with 4xM2e.HSP70c failed to prevent weight loss in challenged mice; they experienced significantly lower weight loss, clinical symptoms and higher lung viral clearance in comparison with protective effects of conventional influenza vaccines in challenged mice. These data demonstrate that C-terminal domain of mHSP70 can be a superior candidate to deliver the adjuvant function in M2e-based influenza A vaccine in order to provide significant protection against multiple influenza A virus strains.

  5. In contrast to conventional inactivated influenza vaccines, 4xM2e.HSP70c fusion protein fully protected mice against lethal dose of H1, H3 and H9 influenza A isolates circulating in Iran

    Energy Technology Data Exchange (ETDEWEB)

    Ebrahimi, Seyyed Mahmoud, E-mail: smebrahimi@shirazu.ac.ir [Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, P.O. Box 14155-3651,Tehran (Iran, Islamic Republic of); Research Center of Virus and Vaccine, Baqiyatallah University of Medical Science, P.O.Box 14155-3651, Tehran (Iran, Islamic Republic of); Dabaghian, Mehran [Department of Pathobiology, University of Tehran, Faculty of Veterinary Medicine, P.O. Box 14155-6453, Tehran (Iran, Islamic Republic of); Tebianian, Majid [Department of Biotechnology, Razi Vaccine and Serum Research Institute (RVSRI), P.O. Box 31975/148, Karaj, Tehran (Iran, Islamic Republic of); Zabeh Jazi, Mohammad Hossein [Department of Pathobiology, University of Tehran, Faculty of Veterinary Medicine, P.O. Box 14155-6453, Tehran (Iran, Islamic Republic of)

    2012-08-15

    Ideal vaccines against influenza viruses should elicit not only a humoral response, but also a cellular response. Mycobacterium tuberculosis HSP70 (mHSP70) have been found to promote immunogenic APCs function, elicit a strong cytotoxic T lymphocyte (CTL) response, and prevent the induction of tolerance. Moreover, it showed linkage of antigens to the C-terminus of mHSP70 (mHSP70c) can represent them as vaccines resulted in more potent, protective antigen specific responses in the absence of adjuvants or complex formulations. Hence, recombinant fusion protein comprising C-terminus of mHSP70 genetically fused to four tandem repeats of the ectodomain of the conserved influenza matrix protein M2 (M2e) was expressed in Escherichia coli, purified under denaturing condition, refolding, and then confirmed by SDS-PAGE, respectively. The recombinant fusion protein, 4xM2e.HSP70c, retained its immunogenicity and displayed the protective epitope of M2e by ELISA and FITC assays. A prime-boost administration of 4xM2e.HSP70c formulated in F105 buffer by intramuscular route in mice (Balb/C) provided full protection against lethal dose of mouse-adapted H1N1, H3N2, or H9N2 influenza A isolates from Iran compared to 0-33.34% survival rate of challenged unimmunized and immunized mice with the currently in use conventional vaccines designated as control groups. However, protection induced by immunization with 4xM2e.HSP70c failed to prevent weight loss in challenged mice; they experienced significantly lower weight loss, clinical symptoms and higher lung viral clearance in comparison with protective effects of conventional influenza vaccines in challenged mice. These data demonstrate that C-terminal domain of mHSP70 can be a superior candidate to deliver the adjuvant function in M2e-based influenza A vaccine in order to provide significant protection against multiple influenza A virus strains.

  6. Serological response to influenza vaccination among children vaccinated for multiple influenza seasons.

    Directory of Open Access Journals (Sweden)

    Sajjad Rafiq

    Full Text Available To evaluate if, among children aged 3 to 15 years, influenza vaccination for multiple seasons affects the proportion sero-protected.Participants were 131 healthy children aged 3-15 years. Participants were vaccinated with trivalent inactivated seasonal influenza vaccine (TIV over the 2005-06, 2006-07 and 2007-8 seasons. Number of seasons vaccinated were categorized as one (2007-08; two (2007-08 and 2006-07 or 2007-08 and 2005-06 or three (2005-06, 2006-07, and 2007-08. Pre- and post-vaccination sera were collected four weeks apart. Antibody titres were determined by hemagglutination inhibition (HAI assay using antigens to A/Solomon Islands/03/06 (H1N1, A/Wisconsin/67/05 (H3N2 and B/Malaysia/2506/04. The proportions sero-protected were compared by number of seasons vaccinated using cut-points for seroprotection of 1:40 vs. 1:320. The proportions of children sero-protected against H1N1 and H3N2 was high (>85% regardless of number of seasons vaccinated and regardless of cut-point for seroprotection. For B Malaysia there was no change in proportions sero-protected by number of seasons vaccinated; however the proportions protected were lower than for H1N1 and H3N2, and there was a lower proportion sero-protected when the higher, compared to lower, cut-point was used for sero-protection.The proportion of children sero-protected is not affected by number of seasons vaccinated.

  7. Safety and immunogenicity of an inactivated cell culture-derived H7N9 influenza vaccine in healthy adults: A phase I/II, prospective, randomized, open-label trial.

    Science.gov (United States)

    Wu, Un-In; Hsieh, Szu-Min; Lee, Wen-Sen; Wang, Ning-Chi; Kung, Hsiang-Chi; Ou, Tsong-Yih; Chen, Fu-Lun; Lin, Te-Yu; Chen, Yee-Chun; Chang, Shan-Chwen

    2017-07-24

    We conducted a phase I/II clinical trial to evaluate the safety and immunogenicity of a Madin-Darby canine kidney (MDCK) cell-grown inactivated H7N9 influenza vaccine for pandemic preparedness purposes. Between April 7, 2015 and May 27, 2016, healthy adults aged 20-60years were enrolled sequentially in phase I (n=40) and phase II (n=160) from three hospitals in Taiwan and randomized to receive 2 doses of whole-virus H7N9 vaccine (15 or 30μg hemagglutinin antigen (HA) with or without an aluminum hydroxide adjuvant) at 21-day intervals. Safety up to 180days and changes in hemagglutinin inhibition (HI) titers at 21days after each vaccination were determined. Of the 200 randomized subjects, 193 (96.5%) received 2 doses of the study vaccine and were included in the intention-to-treat analysis for safety, and 190 (95%) were included in the per-protocol analysis for immunogenicity. Most adverse events were mild and transient; no death or vaccine-related serious adverse events were reported. Overall, higher immune responses were observed in the groups administered with 30μgHA formulation than in the other two groups administered with 15μgHA formulation. The highest immune response was observed in subjects who received 2 doses of the adjuvanted vaccine containing 30μgHA with HI titer, seroprotection rate, seroconversion rate, and seroconversion factor of 36.2, 64.6%, 64.6% and 5.7, respectively. Our study demonstrated that the H7N9 influenza vaccine containing 30µgHA with aluminum hydroxide adjuvant was immunogenic and safe in adults aged 20-60years. CLINICALTRIALS.GOV identifier: NCT02436928. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Enhancement of Th1-biased protective immunity against avian influenza H9N2 virus via oral co-administration of attenuated Salmonella enterica serovar Typhimurium expressing chicken interferon-α and interleukin-18 along with an inactivated vaccine

    Directory of Open Access Journals (Sweden)

    Rahman Md

    2012-07-01

    Full Text Available Abstract Background Control of currently circulating re-assorted low-pathogenicity avian influenza (LPAI H9N2 is a major concern for both animal and human health. Thus, an improved LPAI H9N2 vaccination strategy is needed to induce complete immunity in chickens against LPAI H9N2 virus strains. Cytokines play a crucial role in mounting both the type and extent of an immune response generated following infection with a pathogen or after vaccination. To improve the efficacy of inactivated LPAI H9N2 vaccine, attenuated Salmonella enterica serovar Typhimurium was used for oral co-administration of chicken interferon-α (chIFN-α and chicken interleukin-18 (chIL-18 as natural immunomodulators. Results Oral co-administration of S. enterica serovar Typhimurium expressing chIFN-α and chIL-18, prior to vaccination with inactivated AI H9N2 vaccine, modulated the immune response of chickens against the vaccine antigen through enhanced humoral and Th1-biased cell-mediated immunity, compared to chickens that received single administration of S. enterica serovar Typhimurium expressing either chIFN-α or chIL-18. To further test the protective efficacy of this improved vaccination regimen, immunized chickens were intra-tracheally challenged with a high dose of LPAI H9N2 virus. Combined administration of S. enterica serovar Typhimurium expressing chIFN-α and chIL-18 showed markedly enhanced protection compared to single administration of the construct, as determined by mortality, clinical severity, and feed and water intake. This enhancement of protective immunity was further confirmed by reduced rectal shedding and replication of AIV H9N2 in different tissues of challenged chickens. Conclusions Our results indicate the value of combined administration of chIFN-α and chIL-18 using a Salmonella vaccine strain to generate an effective immunization strategy in chickens against LPAI H9N2.

  9. Moraxella catarrhalis Outer Membrane Vesicles Carry β-Lactamase and Promote Survival of Streptococcus pneumoniae and Haemophilus influenzae by Inactivating Amoxicillin▿

    Science.gov (United States)

    Schaar, Viveka; Nordström, Therése; Mörgelin, Matthias; Riesbeck, Kristian

    2011-01-01

    Moraxella catarrhalis is a common pathogen found in children with upper respiratory tract infections and in patients with chronic obstructive pulmonary disease during exacerbations. The bacterial species is often isolated together with Streptococcus pneumoniae and Haemophilus influenzae. Outer membrane vesicles (OMVs) are released by M. catarrhalis and contain phospholipids, adhesins, and immunomodulatory compounds such as lipooligosaccharide. We have recently shown that M. catarrhalis OMVs exist in patients upon nasopharyngeal colonization. As virtually all M. catarrhalis isolates are β-lactamase positive, the goal of this study was to investigate whether M. catarrhalis OMVs carry β-lactamase and to analyze if OMV consequently can prevent amoxicillin-induced killing. Recombinant β-lactamase was produced and antibodies were raised in rabbits. Transmission electron microscopy, flow cytometry, and Western blotting verified that OMVs carried β-lactamase. Moreover, enzyme assays revealed that M. catarrhalis OMVs contained active β-lactamase. OMVs (25 μg/ml) incubated with amoxicillin for 1 h completely hydrolyzed amoxicillin at concentrations up to 2.5 μg/ml. In functional experiments, preincubation of amoxicillin (10× MIC) with M. catarrhalis OMVs fully rescued amoxicillin-susceptible M. catarrhalis, S. pneumoniae, and type b or nontypeable H. influenzae from β-lactam-induced killing. Our results suggest that the presence of amoxicillin-resistant M. catarrhalis originating from β-lactamase-containing OMVs may pave the way for respiratory pathogens that by definition are susceptible to β-lactam antibiotics. PMID:21576428

  10. Luminescent sulfides of monovalent and trivalent cations

    International Nuclear Information System (INIS)

    1975-01-01

    The invention discloses a family of luminescent materials or phosphors having a rhombohedral crystal structure and consisting essentially of a mixed host sulfide of at least one monovalent host cation and at least one trivalent host cation, and containing, for each mole of phosphor, 0.0005 to 0.05 mole of at least one activating cation. The monovalent host cations may be Na, K or Rb and Cs. The trivalent host cations may be Gd, La, Lu, Sc and Y. The activating cations may be one or more of trivalent As, Bi, Ce, Dy, Er, Pr, Sb, Sm, Tb and Tm; divalent Lu, Mn, Pb and Sn; and monovalent Ag, Cu and Tl. The novel phosphors may be used in devices to convert electron-beam, ultraviolet or x-ray energy to light in the visible spectrum. Such energy conversion can be employed for example in fluoroscopic screens, and in viewing screens of cathode-ray tubes and other electron tubes

  11. Protection against H5N1 Highly Pathogenic Avian and Pandemic (H1N1) 2009 Influenza Virus Infection in Cynomolgus Monkeys by an Inactivated H5N1 Whole Particle Vaccine

    Science.gov (United States)

    Nakayama, Misako; Shichinohe, Shintaro; Itoh, Yasushi; Ishigaki, Hirohito; Kitano, Mitsutaka; Arikata, Masahiko; Pham, Van Loi; Ishida, Hideaki; Kitagawa, Naoko; Okamatsu, Masatoshi; Sakoda, Yoshihiro; Ichikawa, Takaya; Tsuchiya, Hideaki; Nakamura, Shinichiro; Le, Quynh Mai; Ito, Mutsumi; Kawaoka, Yoshihiro; Kida, Hiroshi; Ogasawara, Kazumasa

    2013-01-01

    H5N1 highly pathogenic avian influenza virus (HPAIV) infection has been reported in poultry and humans with expanding clade designations. Therefore, a vaccine that induces immunity against a broad spectrum of H5N1 viruses is preferable for pandemic preparedness. We established a second H5N1 vaccine candidate, A/duck/Hokkaido/Vac-3/2007 (Vac-3), in our virus library and examined the efficacy of inactivated whole particles of this strain against two clades of H5N1 HPAIV strains that caused severe morbidity in cynomolgus macaques. Virus propagation in vaccinated macaques infected with either of the H5N1 HPAIV strains was prevented compared with that in unvaccinated macaques. This vaccine also prevented propagation of a pandemic (H1N1) 2009 virus in macaques. In the vaccinated macaques, neutralization activity, which was mainly shown by anti-hemagglutinin antibody, against H5N1 HPAIVs in plasma was detected, but that against H1N1 virus was not detected. However, neuraminidase inhibition activity in plasma and T-lymphocyte responses in lymph nodes against H1N1 virus were detected. Therefore, cross-clade and heterosubtypic protective immunity in macaques consisted of humoral and cellular immunity induced by vaccination with Vac-3. PMID:24376571

  12. Protection against H5N1 highly pathogenic avian and pandemic (H1N1 2009 influenza virus infection in cynomolgus monkeys by an inactivated H5N1 whole particle vaccine.

    Directory of Open Access Journals (Sweden)

    Misako Nakayama

    Full Text Available H5N1 highly pathogenic avian influenza virus (HPAIV infection has been reported in poultry and humans with expanding clade designations. Therefore, a vaccine that induces immunity against a broad spectrum of H5N1 viruses is preferable for pandemic preparedness. We established a second H5N1 vaccine candidate, A/duck/Hokkaido/Vac-3/2007 (Vac-3, in our virus library and examined the efficacy of inactivated whole particles of this strain against two clades of H5N1 HPAIV strains that caused severe morbidity in cynomolgus macaques. Virus propagation in vaccinated macaques infected with either of the H5N1 HPAIV strains was prevented compared with that in unvaccinated macaques. This vaccine also prevented propagation of a pandemic (H1N1 2009 virus in macaques. In the vaccinated macaques, neutralization activity, which was mainly shown by anti-hemagglutinin antibody, against H5N1 HPAIVs in plasma was detected, but that against H1N1 virus was not detected. However, neuraminidase inhibition activity in plasma and T-lymphocyte responses in lymph nodes against H1N1 virus were detected. Therefore, cross-clade and heterosubtypic protective immunity in macaques consisted of humoral and cellular immunity induced by vaccination with Vac-3.

  13. Inactivated influenza vaccine adjuvanted with bacterium-like particles induce systemic and mucosal influenza A virus specific T-cell and B-cell responses after nasal administration in a TLR2 dependent fashion.

    Science.gov (United States)

    Keijzer, C; Haijema, B J; Meijerhof, T; Voorn, P; de Haan, A; Leenhouts, K; van Roosmalen, M L; van Eden, W; Broere, F

    2014-05-19

    Nasal vaccination is considered to be a promising alternative for parenteral vaccination against influenza virus as it is non-invasive and offers the opportunity to elicit strong antigen-specific responses both systemic and locally at the port of entry of the pathogen. Previous studies showed that non-living bacterium-like particles (BLPs) from the food-grade bacterium Lactococcus lactis are effective stimulators of local and systemic immune responses when administered intranasally. Moreover, in vitro, BLPs specifically interact with human Toll-like receptor 2 (TLR2), suggestive of a role for TLR2 dependent immune activation by BLPs. In the present study, we examined the role of TLR2 in vivo in immune activation after nasal administration of BLP mixed with split influenza vaccine (BLP-SV) of influenza A virus (IAV) using TLR2 knockout mice. The systemic Th1 cell and subsequent B-cell responses induced after intranasal BLP-SV vaccination depended on the interaction of BLPs with TLR2. Notably, the BLP-SV-induced class switch to IgG2c depended on the interaction of BLP with TLR2. Local induced IAV-specific Th1 cell responses and the mucosal B-cell responses also depended on interaction of BLP with TLR2. Strongly reduced SIgA levels were observed in TLR2 knockout mice both in the nasal and vaginal lavages. In addition, detailed analysis of the T-cell response revealed that nasal BLP-SV vaccination promoted Th1/Th17 immune responses that coincided with increased IAV-specific IgG2c antibody production. Altogether these results indicate that nasal BLP-SV vaccination induces IAV-specific T-cell and B-cell responses, both systemically and at the site of virus entry in a TLR2-dependent manner. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  14. Perception and acceptance of intradermal influenza vaccination: Patient reported outcomes from phase 3 clinical trials.

    Science.gov (United States)

    Reygrobellet, Camille; Viala-Danten, Muriel; Meunier, Juliette; Weber, Françoise; Nguyen, Van Hung

    2010-04-01

    An intradermal trivalent inactivated influenza vaccine administered using a microinjection system has received European marketing authorization from the European Medicine Agency. We assessed clinical trial subjects' perception of injection site reactions (ISRs) and whether ISRs affected overall acceptability of vaccination and willingness to be vaccinated in the future. A validated, self-administered, patient reported outcome questionnaire was completed 21 days after intradermal or intramuscular vaccination by elderly and non-elderly adult participants in two European randomized, controlled, open-label phase 3 trials. The questionnaire addressed: the acceptability of ISRs, effect of ISRs on arm movement or sleep, satisfaction with the injection system, and willingness to be revaccinated. Questions were answered using a 5-point Likert verbal rating scale (1 = most favourable, 5 = most unfavourable response). Mean scores were calculated per group. 5,305 questionnaires were completed and analysed (95% return rate). Mean scores were close to 1 in all cases (maximum 1.68), indicating an overall favourable opinion of the vaccination and ISRs. More than 96% of participants rated ISRs after intradermal or intramuscular vaccination as either 'totally acceptable' or 'very acceptable'. Willingness to get vaccinated the following year and satisfaction with the intradermal microinjection system or the conventional intramuscular syringe were high and were not adversely affected by ISRs. ISRs after intradermal influenza vaccine administered using a microinjection system are well accepted by the vaccinees and are generally not a cause for concern.

  15. Vaccine-mismatched influenza B/Yamagata lineage viruses in Cuba, 2012-2013 season.

    Science.gov (United States)

    Arencibia, Amely; Piñón, Alexander; Acosta, Belsy; Fernandez, Leandro; Muné, Mayra; Valdés, Odalys; Savón, Clara; Oropesa, Suset; Gonzalez, Grehete; Roque, Rosmery; Gonzalez, Guelsys; Hernández, Bárbara; Alfonso, Javier Martínez

    2018-03-01

    Annual trivalent influenza vaccines contain one of influenza B lineages; influenza B/Victoria-lineage or influenza B/Yamagata viruses. Theoretically, these vaccines should protect against viruses expected to circulate in the next influenza season. The National Influenza Centers, based on surveillance data from National Reference Laboratories, selects the strains composing each annual trivalent or tetravalent vaccine. Nevertheless, in some epidemics, vaccine strains do not match genetically with circulating strains. The aim of the present study is to compare the HA1-domain of 42 influenza B viruses circulating in Cuba during the 2012-2013 season with the vaccine strain B/Wisconsin/01/2010-like virus from the B/Yamagata lineage, included in the 2012-2013 Northern-Hemisphere Influenza vaccine. The efficacy of the influenza vaccine was also estimated. The analysis of the present study indicates that the B/Victoria and B/Yamagata lineages co-circulated in Cuba in the 2012-2013 season. In 2012-2013 season, according to the sequences analysis, trivalent vaccine did not match with the circulating strains. The present study also detected amino acid substitutions which could have altered the antigenic properties of HA gene. The results presented here suggest the need to consider a possible introduction of tetravalent influenza vaccine in Cuba, as has been recommended by the WHO to ensure higher levels of protection. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. A clinical trial to assess the immunogenicity and safety of Inactivated Influenza Vaccine (Whole Virion IP (Pandemic Influenza (H1N1 2009 Monovalent Vaccine; VaxiFlu-S ™ in healthy Indian adult population

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    A H Kubavat

    2011-01-01

    Full Text Available Background : The pandemic of H1N1 2009 influenza has spread world over and low degree of virus transmission has continued in several regions of India. Aims : To assess the immunogenicity and safety of Pandemic Influenza (H1N1 2009 Monovalent Vaccine in healthy adult Indian population. Settings and Design : Prospective, open label, multicentric, phase 2/3 clinical trial. Materials and Methods : Healthy adult Indian subjects belonging to either 18-59 years or ≥60 years age groups were enrolled and administered a single 0.5 ml (≥15 mcg of hemagglutinin antigen dose of vaccine in the deltoid muscle. Anti-hemagglutinin antibody titer was assessed at baseline and 21 (±2 days after vaccination by Hemagglutination Inhibition (HI test. Safety assessments were done for a period of 42 days. Statistical Analysis Used : Percentages of appropriate population with 95% confidence intervals calculated, log transformation of the data to calculate Geometric Mean Titers (GMTs and chi-square test and student′s t-test applied for significance testing. Results : 182/198 and 53/63 volunteers in age groups of 18-59 years and ≥60 years, respectively, achieved an HI titer ≥1 : 40 at Day 21 (91.9% [95% confidence interval: 88.1-95.7%] and 84.1% [75.1-93.2%]; P=0.072. Further, 171/198 and 50/63 volunteers in the respective age groups achieved seroconversion/four-fold increase in titer at Day 21 (86.4% [81.6-91.1%] and 79.4% [69.4-89.4%]; P=0.179. A significant rise of 22.6-fold [18.0-28.4] and 10.5-fold [7.4-15.0] was noted in GMT in the respective age groups (P<0.001 for both groups as compared to baseline. Nine vaccine-related adverse events were reported (3.4% incidence [1.2-5.6%], which were of low severity only. Conclusions : Pandemic Influenza (H1N1 2009 Monovalent Vaccine produces excellent immunogenic response with a good tolerability profile in adult Indian population.

  17. A Novel Dynamic Model for Health Economic Analysis of Influenza Vaccination in the Elderly.

    Science.gov (United States)

    Mullikin, Mark; Tan, Litjen; Jansen, Jeroen P; Van Ranst, Marc; Farkas, Norbert; Petri, Eckhardt

    2015-12-01

    New vaccines are being developed to improve the efficacy of seasonal influenza immunization in elderly persons aged ≥65 years. These products require clinical and economic evaluation to aid policy decisions. To address this need, a two-part model has been developed, which we have applied to examine the potential clinical and economic impact of vaccinating elderly persons with adjuvanted trivalent inactivated influenza vaccine (aTIV) relative to conventional trivalent (TIV) and quadrivalent (QIV) vaccines. We compared outcomes in the US population for (1) aTIV in persons aged ≥65 years and QIV in all other age cohorts; (2) QIV in all cohorts; (3) TIV in all cohorts. Low, average, and high intensity seasons with low, average, and high vaccine match scenarios were compared. Probabilistic sensitivity analysis was conducted within each discrete scenario to explore the impact of variation in model inputs on potential outcomes. Assuming current vaccination coverage rates in the US population with (a) 25% better efficacy of adjuvanted versus non-adjuvanted vaccine against any strain and (b) 35% better efficacy of non-adjuvanted vaccine against matched B versus mismatched B strains, use of aTIV in persons aged ≥65 years and QIV in persons 54.5% of all circulating strains, use of QIV in all cohorts would offset the clinical benefits of aTIV. Elderly aTIV or QIV vaccination was associated with improved outcomes over non-adjuvanted TIV in many of the scenarios, particularly in low match seasons of any intensity. Total cost savings (including direct and indirect healthcare costs plus productivity impacts) with aTIV in the elderly versus QIV in the whole population ranged from $27 million (low intensity, low match) to $934 million (high intensity, high match). Univariate sensitivity analysis of relative vaccine prices in the average intensity, average match scenario indicated that aTIV could be marginally cost saving relative to QIV at the currently published Medicare

  18. New Wisdom to Defy an Old Enemy: Summary from a scientific symposium at the 4th Influenza Vaccines for the World (IVW) 2012 Congress, 11 October, Valencia, Spain.

    Science.gov (United States)

    Poland, Gregory A; Fleming, Douglas M; Treanor, John J; Maraskovsky, Eugene; Luke, Thomas C; Ball, Emma M A; Poland, Caroline M

    2013-04-17

    Both seasonal and pandemic influenza cause considerable morbidity and mortality globally. In addition, the ongoing threat of new, unpredictable influenza pandemics from emerging variant strains cannot be underestimated. Recently bioCSL (previously known as CSL Biotherapies) sponsored a symposium 'New Wisdom to Defy an Old Enemy' at the 4th Influenza Vaccines for the World Congress in Valencia, Spain. This symposium brought together a renowned faculty of experts to discuss lessons from past experience, novel influenza vaccine developments, and new methods to increase vaccine acceptance and coverage. Specific topics reviewed and discussed included new vaccine development efforts focused on improving efficacy via alternative administration routes, dose modifications, improved adjuvants, and the use of master donor viruses. Improved safety was also discussed, particularly the new finding of an excess of febrile reactions isolated to children who received the 2010 Southern Hemisphere (SH) trivalent inactivated influenza vaccine (TIV). Significant work has been done to both identify the cause and minimize the risk of febrile reactions in children. Other novel prophylactic and therapeutic advances were discussed including immunotherapy. Standard IVIg and hIVIg have been used in ferret studies and human case reports with promising results. New adjuvants, such as ISCOMATRIX™ adjuvant, were noted to provide single-dose, prolonged protection with seasonal vaccine after lethal H5N1 virus challenge in a ferret model of human influenza disease. The data suggest that adjuvanted seasonal influenza vaccines may provide broader protection than unadjuvanted vaccines. The use of an antigen-formulated vaccine to induce broad protection between pandemics that could bridge the gap between pandemic declaration and the production of a homologous vaccine was also discussed. Finally, despite the availability of effective vaccines, most current efforts to increase influenza vaccine coverage

  19. Intranasal delivery of influenza subunit vaccine formulated with GEM particles as an adjuvant

    NARCIS (Netherlands)

    Saluja, Vinay; Amorij, Jean P; van Roosmalen, Maarten L; Leenhouts, Kees; Huckriede, Anke; Hinrichs, Wouter L J; Frijlink, Henderik W

    Nasal administration of influenza vaccine has the potential to facilitate influenza control and prevention. However, when administered intranasally (i.n.), commercially available inactivated vaccines only generate systemic and mucosal immune responses if strong adjuvants are used, which are often

  20. The virosome concept for influenza vaccines

    NARCIS (Netherlands)

    Huckriede, A; Bungener, L; Stegmann, T; Daemen, T; Medema, J; Palache, AM; Wilschut, J

    2005-01-01

    There is a need for more efficacious inactivated influenza vaccines, since current formulations show suboptimal immunogenicity in at-risk populations, like the elderly. More effective vaccines are also urgently needed for an improved influenza pandemic preparedness. In this context, there is

  1. Citric complexes of trivalent cerium and berkelium

    International Nuclear Information System (INIS)

    Boulhassa, S.

    1977-01-01

    The extraction by thenoyltrifluoroacetone (TTA) in benzene of trivalent cerium, berkelium and californium, at the indicator scale, hydrolysis and complexation by citric acid of these cations are studied. The radionuclides used were 144 Ce, 249 Bk and 249 Cf respectively γ, β and α emitters. The solvent extraction technique of the elements by TTA in benzene from a perchloric medium at the ionic stength 0.1 was employed. The distribution coefficients D were measured by the γ, β or α radiometry. Cerium and berkelium, which have a comparable redox behavior, show in solution a relatively stable valency IV. Therefore the study by solvent extraction of their trivalent form required the standing up of complete reducing conditions of these elements and their stabilization in solution at the valency III. The thermodynamic data obtained for berkelium and californium contribute to understand the chemistry of these elements and permit to complete the third 'tetrad branch' of 5f elements from Cm 3+ to Es 3+ . This tetrad effect is a manifestation of thermodynamic consequence of the 'nephelauxetic effect'. As for Ce(III), the data confirm the pronounced acid property and may be show no neglected ligand effect for f 1 configuration [fr

  2. Segurança, imunogenicidade e eficácia da vacina contra o vírus influenza em crianças Safety, immunogenicity and efficacy of influenza vaccine in children

    Directory of Open Access Journals (Sweden)

    Otávio A. L. Cintra

    2006-07-01

    Full Text Available OBJETIVOS: Revisar a imunogenicidade, segurança e eficácia das vacinas trivalentes inativadas e atenuadas contra o vírus influenza em crianças FONTE DOS DADOS: Pesquisa na literatura médica nas bases MEDLINE, LILACS e Biblioteca Cochrane. Artigos de revisão, ensaios clínicos e epidemiológicos foram selecionados para análise no período de 1990 a 2006 SÍNTESE DOS DADOS: A influenza é uma doença infecciosa universal e sazonal que incide em todos os grupos etários e apresenta epidemias anuais caracterizadas por excesso de morbidade e mortalidade. Os idosos e pessoas com comorbidades são grupos de alto risco para influenza grave. Recentemente, foi comprovado que os lactentes saudáveis apresentam morbidade semelhante aos outros grupos de risco, e, portanto, têm indicação para a vacinação contra influenza, que se constitui na ação mais efetiva para a prevenção da infecção por vírus influenza. A segurança das vacinas contra influenza em crianças parece ser adequada, com reações adversas mais observadas do tipo local ou febre. A imunogenicidade em crianças varia de 30 a 90%, sendo diretamente proporcional à idade. A eficácia depende do objetivo primário, podendo ser semelhante ao placebo ou chegar até 91% de eficácia contra infecção comprovada por influenza A. As crianças em idade escolar exercem importante papel na disseminação do vírus influenza, e estudos populacionais mostram imunidade de rebanho. CONCLUSÕES:As vacinas trivalentes contra influenza, inativadas ou atenuadas, são pouco reatogênicas e apresentam imunogenicidade e eficácia variáveis em crianças. A vacinação é efetiva para prevenção de infecção por vírus influenza e para redução de morbidade. Estudos mais potentes de eficácia e segurança em lactentes ainda são desejáveis.OBJECTIVES:To review the immunogenicity, safety and efficacy of inactivated and attenuated trivalent influenza vaccines in children. SOURCES OF DATA: Database

  3. Immunogenicity and tolerability of inactivated flu vaccine In high risk and healthy children Inmunogenicidad y tolerancia de la vacuna inactivada anti-influenza en niños en alto riesgo y en controles sanos

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    Maria Luisa Avila Aguero

    2007-08-01

    Full Text Available We conducted this open study to evaluate the immunogenicity and safety of the inactivated influenza vaccine, Imovax Gripe® in 154 children between 6 and 36 months of age at high risk of influenza- related complications, and in a reference group of 64 healthy children. The study was conducted over two flu seasons, in which the vaccine contained the same A strains but different B strains. The results for the A/H3N2 and A/H1N1 strains from the two flu seasons were pooled, but those for the B strains were not. Anti-hemagglutinin (HA antibody titers were determined before, and one month after each vaccination, and safety was evaluated based on diary card reporting any adverse event observed, either included or not in the list of "solicited events". Within each group of vaccines, the seroconversion rates, seroprotection rates, and ratio of post- to prevaccination geometric mean titers (GMTR for the A/H3N2 and the A/H1N1 strains fulfilled all requirements of the criteria of the European Union Committee for Proprietary Medicinal Products (CPMP. The immune responses in high-risk and in healthy children were similar, and consistent with those observed in previous studies conducted in healthy children. The vaccine was equally well tolerated by all study groups. Reactogenicity was low and similar in both high-risk and healthy children. Overall from 9.5% to 15.4% of at-risk children and 12% of healthy children reported a solicited local reaction; 23.0 to 28.8% of high-risk and 25.3% of healthy children reported a solicited systemic reaction. The study results provide support for vaccination of children at high-risk of influenza related complications.Se realizó un estudio clínico abierto para evaluar la inmunogenícidad y la seguridad de la vacuna inactivada anti-influenza, Imovax Gripe®, en 154 niños entre 6 y 36 meses de edad con alto riesgo de complicaciones ligadas a la influenza, y en un grupo de referencia de 64 niños sanos. El estudio fue

  4. Antibody persistence 1 year after pandemic H1N1 2009 influenza vaccination and immunogenicity of subsequent seasonal influenza vaccine among adult organ transplant patients.

    Science.gov (United States)

    Felldin, Marie; Andersson, Bengt; Studahl, Marie; Svennerholm, Bo; Friman, Vanda

    2014-02-01

    We investigated the antibody persistence in solid organ transplant (SOT) recipients 1 year after immunization with two doses of monovalent AS03-adjuvanted influenza A(H1N1)pdm09 vaccine. We also assessed the boosting effect of the seasonal trivalent inactivated vaccine 2010 (TIV/10) that contained the influenza A(H1N1)pdm09 strain. A total of 49 SOT recipients and 11 healthy controls were included. After a blood sample was obtained to assess the persistent immunity, one dose of TIV/10 was administered and another blood sample was collected 1 month after vaccination. A(H1N1)pdm09 antibodies were measured using a haemagglutination inhibition assay. The percentage of SOT recipients with protective titres decreased between 1 month and 10-14 months after the monovalent influenza A(H1N1)pdm09 vaccination, from 79% (n = 38) to 47% (n = 23) (P = 0.02). The corresponding numbers for the control group were 100% and 63%, respectively (P = 0.008). After the TIV/10 boosting dose, the number of SOT recipients with protective titres increased from 47% (n = 23) to 71% (n = 35) (P = 0.2). All the controls reached a protective titre level. The median titre rise was significantly higher among controls when compared to SOT recipients (P = 0.0036). No rejection or adverse events were seen. The results show an obvious need for vaccine boosting doses in the SOT patients. © 2013 Steunstichting ESOT. Published by John Wiley & Sons Ltd.

  5. Age and Influenza-Specific Pre-Vaccination Antibodies Strongly Affect Influenza Vaccine Responses in the Icelandic Population whereas Disease and Medication Have Small Effects

    Science.gov (United States)

    Olafsdottir, Thorunn A.; Alexandersson, Kristjan F.; Sveinbjornsson, Gardar; Lapini, Giulia; Palladino, Laura; Montomoli, Emanuele; Del Giudice, Giuseppe; Gudbjartsson, Daniel F.; Jonsdottir, Ingileif

    2018-01-01

    Influenza vaccination remains the best strategy for the prevention of influenza virus-related disease and reduction of disease severity and mortality. However, there is large individual variation in influenza vaccine responses. In this study, we investigated the effects of gender, age, underlying diseases, and medication on vaccine responses in 1,852 Icelanders of broad age range who received trivalent inactivated influenza virus vaccination in 2012, 2013, or 2015. Hemagglutination inhibition (HAI) and microneutralization (MN) titers were measured in pre- and post-vaccination sera. Of the variables tested, the strongest association was with level of pre-vaccination titer that explained a major part of the variance observed in post-vaccination titers, ranging from 19 to 29%, and from 7 to 21% in fold change (FC), depending on the strain and serological (HAI or MN) analysis performed. Thus, increasing pre-vaccination titer associated with decreasing FC (P = 1.1 × 10−99–8.6 × 10−30) and increasing post-vaccination titer (P = 2.1 × 10−159–1.1 × 10−123). Questionnaires completed by 87% of the participants revealed that post-vaccination HAI titer showed association with repeated previous influenza vaccinations. Gender had no effect on vaccine response whereas age had a strong effect and explained 1.6–3.1% of HAI post-vaccination titer variance and 3.1% of H1N1 MN titer variance. Vaccine response, both fold increase and seroprotection rate (percentage of individuals reaching HAI ≥ 40 or MN ≥ 20), was higher in vaccinees ≤37 years of age (YoA) than all other age groups. Furthermore, a reduction was observed in the H1N1 MN titer in people ≥63 YoA, demonstrating a decreased neutralizing functionality of vaccine-induced antibodies at older age. We tested the effects of underlying autoimmune diseases, asthma and allergic diseases and did not observe significant associations with vaccine responses. Intake of immune

  6. Age and Influenza-Specific Pre-Vaccination Antibodies Strongly Affect Influenza Vaccine Responses in the Icelandic Population whereas Disease and Medication Have Small Effects

    Directory of Open Access Journals (Sweden)

    Thorunn A. Olafsdottir

    2018-01-01

    Full Text Available Influenza vaccination remains the best strategy for the prevention of influenza virus-related disease and reduction of disease severity and mortality. However, there is large individual variation in influenza vaccine responses. In this study, we investigated the effects of gender, age, underlying diseases, and medication on vaccine responses in 1,852 Icelanders of broad age range who received trivalent inactivated influenza virus vaccination in 2012, 2013, or 2015. Hemagglutination inhibition (HAI and microneutralization (MN titers were measured in pre- and post-vaccination sera. Of the variables tested, the strongest association was with level of pre-vaccination titer that explained a major part of the variance observed in post-vaccination titers, ranging from 19 to 29%, and from 7 to 21% in fold change (FC, depending on the strain and serological (HAI or MN analysis performed. Thus, increasing pre-vaccination titer associated with decreasing FC (P = 1.1 × 10−99–8.6 × 10−30 and increasing post-vaccination titer (P = 2.1 × 10−159–1.1 × 10−123. Questionnaires completed by 87% of the participants revealed that post-vaccination HAI titer showed association with repeated previous influenza vaccinations. Gender had no effect on vaccine response whereas age had a strong effect and explained 1.6–3.1% of HAI post-vaccination titer variance and 3.1% of H1N1 MN titer variance. Vaccine response, both fold increase and seroprotection rate (percentage of individuals reaching HAI ≥ 40 or MN ≥ 20, was higher in vaccinees ≤37 years of age (YoA than all other age groups. Furthermore, a reduction was observed in the H1N1 MN titer in people ≥63 YoA, demonstrating a decreased neutralizing functionality of vaccine-induced antibodies at older age. We tested the effects of underlying autoimmune diseases, asthma and allergic diseases and did not observe significant associations with vaccine responses. Intake

  7. Reverse Genetics Approaches for the Development of Influenza Vaccines

    Science.gov (United States)

    Nogales, Aitor; Martínez-Sobrido, Luis

    2016-01-01

    Influenza viruses cause annual seasonal epidemics and occasional pandemics of human respiratory disease. Influenza virus infections represent a serious public health and economic problem, which are most effectively prevented through vaccination. However, influenza viruses undergo continual antigenic variation, which requires either the annual reformulation of seasonal influenza vaccines or the rapid generation of vaccines against potential pandemic virus strains. The segmented nature of influenza virus allows for the reassortment between two or more viruses within a co-infected cell, and this characteristic has also been harnessed in the laboratory to generate reassortant viruses for their use as either inactivated or live-attenuated influenza vaccines. With the implementation of plasmid-based reverse genetics techniques, it is now possible to engineer recombinant influenza viruses entirely from full-length complementary DNA copies of the viral genome by transfection of susceptible cells. These reverse genetics systems have provided investigators with novel and powerful approaches to answer important questions about the biology of influenza viruses, including the function of viral proteins, their interaction with cellular host factors and the mechanisms of influenza virus transmission and pathogenesis. In addition, reverse genetics techniques have allowed the generation of recombinant influenza viruses, providing a powerful technology to develop both inactivated and live-attenuated influenza vaccines. In this review, we will summarize the current knowledge of state-of-the-art, plasmid-based, influenza reverse genetics approaches and their implementation to provide rapid, convenient, safe and more effective influenza inactivated or live-attenuated vaccines. PMID:28025504

  8. Cost-effectiveness analysis of different seasonal influenza vaccines in the elderly Italian population.

    Science.gov (United States)

    Capri, Stefano; Barbieri, Marco; de Waure, Chiara; Boccalini, Sara; Panatto, Donatella

    2018-02-09

    ABSRACT In the perspective of reaching at least 75% influenza vaccination coverage in the elderly and substantial budget constraints, Italian decision makers are facing important challenges in determining an optimal immunization strategy for this growing and particularly vulnerable population. Four different influenza vaccines are currently available for Italian older adults aged 65 years or above, namely trivalent inactivated vaccines (TIVs), MF59-adjuvanted TIV (MF59-TIV), intradermal TIV (ID-TIV) and quadrivalent inactivated vaccines (QIVs). The present study is the first to compare the cost-effectiveness profiles of virtually all possible public health strategies, including the aforementioned four vaccine formulations as well non-vaccination. For this purpose, a decision tree model was built ex novo; the analysis was conducted from the third-payer perspective in the timeframe of one year. All available vaccines were cost-effective compared with non-vaccination. However, MF59-TIV had the most favorable economic profile in the Italian elderly population. Indeed, compared with non-vaccination, it was deemed highly cost-effective with an incremental cost-effectiveness ratio (ICER) of €10,750 per quality-adjusted life year (QALY). The ICER was much lower (€4,527/QALY) when MF59-TIV was directly compared with TIV. ID-TIV and QIV were dominated by MF59-TIV as the former comparators were associated with greater total costs and lower health benefits. Both deterministic and probabilistic sensitivity analyses confirmed robustness of the base case results. From the economic perspective, MF59-TIV should be considered as a preferential choice for Italian older adults aged 65 years or above.

  9. Post licensure surveillance of influenza vaccines in the Vaccine Safety Datalink in the 2013-2014 and 2014-2015 seasons.

    Science.gov (United States)

    Li, Rongxia; Stewart, Brock; McNeil, Michael M; Duffy, Jonathan; Nelson, Jennifer; Kawai, Alison Tse; Baxter, Roger; Belongia, Edward A; Weintraub, Eric

    2016-08-01

    The changes in each year in influenza vaccine antigenic components as well as vaccine administration patterns may pose new risks of adverse events following immunization (AEs). To evaluate the safety of influenza vaccines annually administered to people ≥ 6 months, we conducted weekly post licensure surveillance for seven pre-specified adverse events following receipt of influenza vaccines during the 2013-2014 and 2014-2015 seasons in the Vaccine Safety Datalink (VSD). We used both a historically-controlled cohort design with the Poisson-based maximized sequential probability ratio test (maxSPRT) and a self-controlled risk interval (SCRI) design with the binomial-based maxSPRT. For each adverse event outcome, we defined the risk interval on the basis of biologic plausibility and prior literature. For the historical cohort design, numbers of expected adverse events were calculated from the prior seven seasons, adjusted for age and site. For the SCRI design, a comparison window was defined either before vaccination or after vaccination, depending on each specific outcome. An elevated risk of febrile seizures 0-1 days following trivalent inactivated influenza vaccine (IIV3) was identified in children aged 6-23 months during the 2014-2015 season using the SCRI design. We found the relative risk (RR) of febrile seizures following concomitant administration of IIV3 and PCV13 was 5.3 with a 95% CI 1.87-14.75. Without concomitant PCV 13 administration, the estimated risk decreased and was no longer statistically significant (RR: 1.4; CI: 0.54 - 3.61). No increased risks, other than for febrile seizures, were identified in influenza vaccine safety surveillance during 2013-2014 and 2014-2015 seasons in the VSD. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  10. Heterovariant Cross-Reactive B-Cell Responses Induced by the 2009 Pandemic Influenza Virus A Subtype H1N1 Vaccine

    Science.gov (United States)

    He, Xiao-Song; Sasaki, Sanae; Baer, Jane; Khurana, Surender; Golding, Hana; Treanor, John J.; Topham, David J.; Sangster, Mark Y.; Jin, Hong; Dekker, Cornelia L.; Subbarao, Kanta; Greenberg, Harry B.

    2013-01-01

    Background. The generation of heterovariant immunity is a highly desirable feature of influenza vaccines. The goal of this study was to compare the heterovariant B-cell response induced by the monovalent inactivated 2009 pandemic influenza A virus subtype H1N1 (A[H1N1]pdm09) vaccine with that induced by the 2009 seasonal trivalent influenza vaccine (sTIV) containing a seasonal influenza A virus subtype H1N1 (A[H1N1]) component in young and elderly adults. Methods. Plasmablast-derived polyclonal antibodies (PPAb) from young and elderly recipients of A(H1N1)pdm09 vaccine or sTIV were tested for binding activity to various influenza antigens. Results. In A(H1N1)pdm09 recipients, the PPAb titers against homotypic A(H1N1)pdm09 vaccine were similar to those against the heterovariant seasonal A(H1N1) vaccine and were similar between young and elderly subjects. The PPAb avidity was higher among elderly individuals, compared with young individuals. In contrast, the young sTIV recipients had 10-fold lower heterovariant PPAb titers against the A(H1N1)pdm09 vaccine than against the homotypic seasonal A(H1N1) vaccine. In binding assays with recombinant head and stalk domains of hemagglutinin, PPAb from the A(H1N1)pdm09 recipients but not PPAb from the sTIV recipients bound to the conserved stalk domain. Conclusion. The A(H1N1)pdm09 vaccine induced production of PPAb with heterovariant reactivity, including antibodies targeting the conserved hemagglutinin stalk domain. PMID:23107783

  11. Impact of quadrivalent influenza vaccine on public health and influenza-related costs in Australia

    Directory of Open Access Journals (Sweden)

    Aurélien Jamotte

    2016-07-01

    Full Text Available Abstract Background Annual trivalent influenza vaccines (TIV containing three influenza strains (A/H1N1, A/H3N2, and one B have been recommended for the prevention of influenza. However, worldwide co-circulation of two distinct B lineages (Victoria and Yamagata and difficulties in predicting which lineage will predominate each season have led to the development of quadrivalent influenza vaccines (QIV, which include both B lineages. Our analysis evaluates the public health benefit and associated influenza-related costs avoided which would have been obtained by using QIV rather than TIV in Australia over the period 2002–2012. Methods A static model stratified by age group was used, focusing on people at increased risk of influenza as defined by the Australian vaccination recommendations. B-lineage cross-protection was accounted for. We calculated the potential impact of QIV compared with TIV over the seasons 2002–2012 (2009 pandemic year excluded using Australian data on influenza circulation, vaccine coverage, hospitalisation and mortality rates as well as unit costs, and international data on vaccine effectiveness, influenza attack rate, GP consultation rate and working days lost. Third-party payer and societal influenza-related costs were estimated in 2014 Australian dollars. Sensitivity analyses were conducted. Results Using QIV instead of TIV over the period 2002–2012 would have prevented an estimated 68,271 additional influenza cases, 47,537 GP consultations, 3,522 hospitalisations and 683 deaths in the population at risk of influenza. These results translate into influenza-related societal costs avoided of $46.5 million. The estimated impact of QIV was higher for young children and the elderly. The overall impact of QIV depended mainly on vaccine effectiveness and the influenza attack rate attributable to the mismatched B lineage. Conclusion The broader protection offered by QIV would have reduced the number of influenza infections

  12. Reverse Genetics of Influenza B Viruses.

    Science.gov (United States)

    Nogales, Aitor; Perez, Daniel R; Santos, Jefferson; Finch, Courtney; Martínez-Sobrido, Luis

    2017-01-01

    Annual influenza epidemics are caused not only by influenza A viruses but also by influenza B viruses. Initially established for the generation of recombinant influenza A viruses, plasmid-based reverse genetics techniques have allowed researchers the generation of wild type and mutant viruses from full-length cDNA copies of the influenza viral genome. These reverse genetics approaches have allowed researchers to answer important questions on the biology of influenza viruses by genetically engineering infectious recombinant viruses. This has resulted in a better understanding of the molecular biology of influenza viruses, including both viral and host factors required for genome replication and transcription. With the ability to generate recombinant viruses containing specific mutations in the viral genome, these reverse genetics tools have also allowed the identification of viral and host factors involved in influenza pathogenesis, transmissibility, host-range interactions and restrictions, and virulence. Likewise, reverse genetics techniques have been used for the implementation of inactivated or live-attenuated influenza vaccines and the identification of anti-influenza drugs and their mechanism of antiviral activity. In 2002, these reverse genetics approaches allowed also the recovery of recombinant influenza B viruses entirely from plasmid DNA. In this chapter we describe the cloning of influenza B/Brisbane/60/2008 viral RNAs into the ambisense pDP-2002 plasmid and the experimental procedures for the successful generation of recombinant influenza B viruses.

  13. Adverse events following pandemic influenza A (H1N1) 2009 monovalent and seasonal influenza vaccinations during the 2009-2010 season in the active component U.S. military and civilians aged 17-44years reported to the Vaccine Adverse Event Reporting System.

    Science.gov (United States)

    Bardenheier, Barbara H; Duderstadt, Susan K; Engler, Renata J M; McNeil, Michael M

    2016-08-17

    No comparative review of Vaccine Adverse Event Reporting System (VAERS) submissions following pandemic influenza A (H1N1) 2009 and seasonal influenza vaccinations during the pandemic season among U.S. military personnel has been published. We compared military vs. civilian adverse event reporting rates. Adverse events (AEs) following vaccination were identified from VAERS for adults aged 17-44years after pandemic (monovalent influenza [MIV], and seasonal (trivalent inactivated influenza [IIV3], live attenuated influenza [LAIV3]) vaccines. Military vaccination coverage was provided by the Department of Defense's Defense Medical Surveillance System. Civilian vaccination coverage was estimated using data from the National 2009 H1N1 Flu Survey and the Behavioral Risk Factor Surveillance System survey. Vaccination coverage was more than four times higher for MIV and more than twenty times higher for LAIV3 in the military than in the civilian population. The reporting rate of serious AE reports following MIV in service personnel (1.19 per 100,000) was about half that reported by the civilian population (2.45 per 100,000). Conversely, the rate of serious AE reports following LAIV3 among service personnel (1.32 per 100,000) was more than twice that of the civilian population. Although fewer military AEs following MIV were reported overall, the rate of Guillain-Barré Syndrome (GBS) (4.01 per million) was four times greater than that in the civilian population. (1.04 per million). Despite higher vaccination coverage in service personnel, the rate of serious AEs following MIV was about half that in civilians. The rate of GBS reported following MIV was higher in the military. Published by Elsevier Ltd.

  14. Virus-Vectored Influenza Virus Vaccines

    Science.gov (United States)

    Tripp, Ralph A.; Tompkins, S. Mark

    2014-01-01

    Despite the availability of an inactivated vaccine that has been licensed for >50 years, the influenza virus continues to cause morbidity and mortality worldwide. Constant evolution of circulating influenza virus strains and the emergence of new strains diminishes the effectiveness of annual vaccines that rely on a match with circulating influenza strains. Thus, there is a continued need for new, efficacious vaccines conferring cross-clade protection to avoid the need for biannual reformulation of seasonal influenza vaccines. Recombinant virus-vectored vaccines are an appealing alternative to classical inactivated vaccines because virus vectors enable native expression of influenza antigens, even from virulent influenza viruses, while expressed in the context of the vector that can improve immunogenicity. In addition, a vectored vaccine often enables delivery of the vaccine to sites of inductive immunity such as the respiratory tract enabling protection from influenza virus infection. Moreover, the ability to readily manipulate virus vectors to produce novel influenza vaccines may provide the quickest path toward a universal vaccine protecting against all influenza viruses. This review will discuss experimental virus-vectored vaccines for use in humans, comparing them to licensed vaccines and the hurdles faced for licensure of these next-generation influenza virus vaccines. PMID:25105278

  15. Assessment of immune response in cattle against experimentally prepared trivalent (O, A, and Asia-1 FMD vaccine in Bangladesh

    Directory of Open Access Journals (Sweden)

    Md. Mashfiqur Rahman Chowdhury

    2015-12-01

    Full Text Available This research work was conducted to investigate the effects of age, sex and breed on the induction of immune response against experimentally prepared inactivated trivalent (type O, A, and Asia-1 FMD vaccine. Twenty six cattle were divided into four test groups (Group A, B, C, and D; 5 cattle in each group and one control group (n=6 based on breed (local and cross, age (≤12 months and >12 months, and sex (male and female. Test cattle were vaccinated with the experimentally prepared trivalent FMD vaccine. Pre- and post vaccinated sera from the vaccinated cattle were collected upto 63 days, and the sera were tested using liquid phase blocking enzyme linked immunosorbent assay (LPBE that was specific for FMD serotypes O, A, and Asia-1. Antibody titers of all the pre-vaccinated serum samples were found to be under protection level. The females were found to be more protected (90%; n=9/10 as compared to males (70%; n=7/10. The titers obtained were statistically analyzed using t–test to observe the effects of age, breed and sex. It was observed that the mean values of antibody titer in cattle aging >12 months against O, A, and Asia-1 serotypes were significant (P12 months showed better immune response towards trivalent FMD vaccine.

  16. Chelation of di- and trivalent iron with some polyaminopolycarboxylic acids

    International Nuclear Information System (INIS)

    Hafez, M.B.; Sharabi, Nahid; Patti, Francois.

    1979-02-01

    The chelation of di- and trivalent iron with some polyaminopolycarboxylic acids was studied. The influence of pH on the formation of the complex was investigated, the molecular ratio and the stability constants were determined [fr

  17. Guillain-Barré Syndrome, Influenza Vaccination, and Antecedent Respiratory and Gastrointestinal Infections: A Case-Centered Analysis in the Vaccine Safety Datalink, 2009-2011.

    Directory of Open Access Journals (Sweden)

    Sharon K Greene

    Full Text Available Guillain-Barré Syndrome (GBS can be triggered by gastrointestinal or respiratory infections, including influenza. During the 2009 influenza A (H1N1 pandemic in the United States, monovalent inactivated influenza vaccine (MIV availability coincided with high rates of wildtype influenza infections. Several prior studies suggested an elevated GBS risk following MIV, but adjustment for antecedent infection was limited.We identified patients enrolled in health plans participating in the Vaccine Safety Datalink and diagnosed with GBS from July 2009 through June 2011. Medical records of GBS cases with 2009-10 MIV, 2010-11 trivalent inactivated influenza vaccine (TIV, and/or a medically-attended respiratory or gastrointestinal infection in the 1 through 141 days prior to GBS diagnosis were reviewed and classified according to Brighton Collaboration criteria for diagnostic certainty. Using a case-centered design, logistic regression models adjusted for patient-level time-varying sources of confounding, including seasonal vaccinations and infections in GBS cases and population-level controls.Eighteen confirmed GBS cases received vaccination in the 6 weeks preceding onset, among 1.27 million 2009-10 MIV recipients and 2.80 million 2010-11 TIV recipients. Forty-four confirmed GBS cases had infection in the 6 weeks preceding onset, among 3.77 million patients diagnosed with medically-attended infection. The observed-versus-expected odds that 2009-10 MIV/2010-11 TIV was received in the 6 weeks preceding GBS onset was odds ratio = 1.54, 95% confidence interval (CI, 0.59-3.99; risk difference = 0.93 per million doses, 95% CI, -0.71-5.16. The association between GBS and medically-attended infection was: odds ratio = 7.73, 95% CI, 3.60-16.61; risk difference = 11.62 per million infected patients, 95% CI, 4.49-26.94. These findings were consistent in sensitivity analyses using alternative infection definitions and risk intervals for prior

  18. Assessment of Public Health and Economic Impact of Intranasal Live-Attenuated Influenza Vaccination of Children in France Using a Dynamic Transmission Model.

    Science.gov (United States)

    Gerlier, L; Lamotte, M; Grenèche, S; Lenne, X; Carrat, F; Weil-Olivier, C; Damm, O; Schwehm, M; Eichner, M

    2017-04-01

    We estimated the epidemiological and economic impact of extending the French influenza vaccination programme from at-risk/elderly (≥65 years) only to healthy children (2-17 years). A deterministic, age-structured, dynamic transmission model was used to simulate the transmission of influenza in the French population, using the current vaccination coverage with trivalent inactivated vaccine (TIV) in at-risk/elderly individuals (current strategy) or gradually extending the vaccination to healthy children (aged 2-17 years) with intranasal, quadrivalent live-attenuated influenza vaccine (QLAIV) from current uptake up to 50% (evaluated strategy). Epidemiological, medical resource use and cost data were taken from international literature and country-specific information. The model was calibrated to the observed numbers of influenza-like illness visits/year. The 10-year number of symptomatic cases of confirmed influenza and direct medical costs ('all-payer') were calculated for the 0-17- (direct and indirect effects) and ≥18-year-old (indirect effect). The incremental cost-effectiveness ratio (ICER) was calculated for the total population, using a 4% discount rate/year. Assuming 2.3 million visits/year and 1960 deaths/year, the model calibration yielded an all-year average basic reproduction number (R 0 ) of 1.27. In the population aged 0-17 years, QLAIV prevented 865,000 influenza cases/year (58.4%), preventing 10-year direct medical expenses of €374 million. In those aged ≥18 years with unchanged TIV coverage, 1.2 million cases/year were averted (27.6%) via indirect effects (additionally prevented expenses, €457 million). On average, 613 influenza-related deaths were averted annually overall. The ICER was €18,001/life-year gained. The evaluated strategy had a 98% probability of being cost-effective at a €31,000/life-year gained threshold. The model demonstrated strong direct and indirect benefits of protecting healthy children against influenza with

  19. Effectiveness of inactivated quadrivalent influenza vaccine in the 2015/2016 season as assessed in both a test-negative case-control study design and a traditional case-control study design.

    Science.gov (United States)

    Kimiya, Takahisa; Shinjoh, Masayoshi; Anzo, Makoto; Takahashi, Hiroki; Sekiguchi, Shinichiro; Sugaya, Norio; Takahashi, Takao

    2018-04-21

    Both traditional case-control studies (TCCSs) and test-negative case-control studies (TNCCSs) are commonly used to assess influenza vaccine effectiveness (VE). To compensate for the fact that observational studies are susceptible to bias, we combined both methods to assess VE in one geographical area during the 2015/2016 season, when influenza A (H1N1)pdm was dominant. Our TNCCS covered 331 children aged 6 months to 15 years who visited our hospital with fever, including 182 with influenza, and our TCCS covered 812 pediatric outpatients aged 6 months to 15 years, including 214 with influenza. Influenza infection and vaccination history were reviewed, and VE was calculated as (1 - odds ratio) × 100. In the TNCCS, VE against influenza A was 68% (95% CI 47-81) overall, and 70% (48-83) for those given two doses; against influenza B, VE was 37% (- 12-64) overall and 49% (2-74) for two doses. In the TCCS, VE against influenza A was 44% (15-63) overall and 44% (13-64) for two doses, and VE against influenza B was 24% (- 19-52) overall and 41% (3-64) for two doses. Both studies confirmed significant VE against influenza A, significant two-dose VE against influenza B, and better two-dose VE than one-dose VE. What is Known: • Influenza vaccine effectiveness (VE) varies from year to year. • Observational studies are conventionally used for VE assessment. However, they are inherently susceptible to bias and confounding. What is New: • This is the first report of influenza VE assessment using more than one observational study and performed in a specific area during the same season. • VE estimates obtained in our traditional case-control study were lower than those in our test-negative case-control study, but both studies found significant VE against influenza.

  20. Abnormal humoral immune response to influenza vaccination in pediatric type-1 human immunodeficiency virus infected patients receiving highly active antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Carlos J Montoya

    2007-06-01

    Full Text Available Given that highly active antiretroviral therapy (HAART has been demonstrated useful to restore immune competence in type-1 human immunodeficiency virus (HIV-1-infected subjects, we evaluated the specific antibody response to influenza vaccine in a cohort of HIV-1-infected children on HAART so as to analyze the quality of this immune response in patients under antiretroviral therapy. Sixteen HIV-1-infected children and 10 HIV-1 seronegative controls were immunized with a commercially available trivalent inactivated influenza vaccine containing the strains A/H1N1, A/H3N2, and B. Serum hemagglutinin inhibition (HI antibody titers were determined for the three viral strains at the time of vaccination and 1 month later. Immunization induced a significantly increased humoral response against the three influenza virus strains in controls, and only against A/H3N2 in HIV-1-infected children. The comparison of post-vaccination HI titers between HIV-1+ patients and HIV-1 negative controls showed significantly higher HI titers against the three strains in controls. In addition, post vaccination protective HI titers (defined as equal to or higher than 1:40 against the strains A/H3N2 and B were observed in a lower proportion of HIV-1+ children than in controls, while a similar proportion of individuals from each group achieved protective HI titers against the A/H1N1 strain. The CD4+ T cell count, CD4/CD8 T cells ratio, and serum viral load were not affected by influenza virus vaccination when pre- vs post-vaccination values were compared. These findings suggest that despite the fact that HAART is efficient in controlling HIV-1 replication and in increasing CD4+ T cell count in HIV-1-infected children, restoration of immune competence and response to cognate antigens remain incomplete, indicating that additional therapeutic strategies are required to achieve a full reconstitution of immune functions.

  1. Incompatibility of lyophilized inactivated polio vaccine with liquid pentavalent whole-cell-pertussis-containing vaccine

    NARCIS (Netherlands)

    Kraan, H.; Have, Ten R.; Maas, van der L.; Kersten, G.F.A.; Amorij, J.P.

    2016-01-01

    A hexavalent vaccine containing diphtheria toxoid, tetanus toxoid, whole cell pertussis, Haemophilius influenza type B, hepatitis B and inactivated polio vaccine (IPV) may: (i) increase the efficiency of vaccination campaigns, (ii) reduce the number of injections thereby reducing needlestick

  2. Safety of quadrivalent live attenuated influenza vaccine in subjects aged 2-49years.

    Science.gov (United States)

    Baxter, Roger; Eaton, Abigail; Hansen, John; Aukes, Laurie; Caspard, Herve; Ambrose, Christopher S

    2017-03-01

    Quadrivalent live attenuated influenza vaccine (Q/LAIV) was licensed in 2012 and replaced trivalent live attenuated influenza vaccine in the United States during the 2013-2014 influenza season. This study assessed the safety of Q/LAIV in children and adults aged 2-49years. This was a prospective observational cohort study using data collected from Kaiser Permanente Northern California. Post-vaccination events of interest were any hospitalization, hospitalization for lower respiratory tract infection, and the following medically attended events: hypersensitivity, seizures/convulsions, lower respiratory tract infection, wheezing, Guillain-Barré syndrome, Bell's palsy, encephalitis, neuritis, vasculitis, and narcolepsy/cataplexy. The rates of these events during the risk interval post-vaccination were compared with rates observed during reference periods later in the follow-up (within-cohort analysis) and with rates observed in frequency-matched unvaccinated controls and inactivated influenza vaccine (IIV) recipients. A total of 62,040 eligible Q/LAIV recipients were identified during the 2013-2014 influenza season. Within-cohort comparisons of all Q/LAIV recipients as well as comparisons between Q/LAIV recipients and unvaccinated controls or IIV recipients did not show any significantly higher risk of hospitalizations or medically attended events following administration of Q/LAIV. Additional analyses by setting (clinic visits, emergency department visits, and hospital admissions) and age group (2-4, 5-8, 9-17, and 18-49years) also did not reveal clinically consistent findings that suggested any increased risk after administration of Q/LAIV. In this large population study of individuals aged 2-49years, no safety signals associated with the administration of Q/LAIV were observed. A much larger study population would be needed to confidently reject any association between Q/LAIV and very rare events, specifically those with an incidence of <1 event/10,000 person

  3. The priming effect of previous natural pandemic H1N1 infection on the immunogenicity to subsequent 2010-2011 influenza vaccination in children: a prospective cohort study.

    Science.gov (United States)

    Kang, Eun Kyeong; Eun, Byung Wook; Kim, Nam Hee; Lim, Jung Sub; Lee, Jun Ah; Kim, Dong Ho

    2016-08-22

    The effect of previous natural pandemic H1N1 (H1N1 pdm09) influenza infection on the immunogenicity to subsequent inactivated influenza vaccination in children has not been well studied. We aimed to evaluate the effect of H1N1 pdm09 natural infection and vaccination on the immunogenicity to subsequent 2010-2011 seasonal inactivated influenza vaccination in children. From October 2010 to May 2011, we conducted an open-label, multi-center study in children aged 6 months -18 years in Korea. We measured antibody titers with a hemagglutination-inhibition (HI) assay at baseline, 1 month, and 6 months after vaccination with trivalent split or subunit vaccines containing H1N1 pdm, A/H3N2, and B. The subjects were classified into 4 groups depending on the presence of laboratory-confirmed H1N1 pdm09 infection and/or vaccination in the 2009-2010 season; Group I: vaccination (-)/infection(-), Group II: vaccination (-)/infection(+), Group III: vaccination (+)/infection(-), Group IV: vaccination (+)/infection(+). Among the subjects in group I, 47 subjects who had a baseline titer >1:10 were considered to have an asymptomatic infection. They were included into the final group II (n = 80). We defined the new group II as the infection-primed (IP) group and group III as the vaccine-primed (VP) group. Seroconversion rate (57.5 % vs 35.9 %, p = 0.001), seroprotection rate at 6 months after vaccination (70.8 % vs 61.8 %, p = 0.032), and GMT at 1 month after vaccination (129.9 vs 66.5, p = 0.002) were significantly higher in the IP group than in the VP group. In the 9-18 year-old group, seroconversion rate and immunogenicity at 1 and 6 months were significantly higher in the IP group than in the VP group. However in the 1-7 year-old age group, there was no significant difference between the two groups. Previous H1N1 pdm09 infection appears to have positive effects on immunogenicity of subsequent inactivated influenza vaccines against H1N1 pdm09 in older

  4. Influenza vaccination

    DEFF Research Database (Denmark)

    Østerhus, Sven Frederick

    2015-01-01

    The Cochrane Library was systematically searched for meta-analyses regarding influenza vaccination of various populations, both healthy and sick. An effect in reducing the number of cases of influenza, influenza-like illness or complications to influenza was found in some studies, but, generally......, the quality of the studies was low, and several studies lacked hard clinical endpoints. Data on adverse effects were scarce. More randomised controlled trials investigating the effects of influenza vaccination are warranted....

  5. [Influenza vaccine and adjuvant].

    Science.gov (United States)

    Nakayama, Tetsuo

    2011-01-01

    Adjuvant is originated from the Latin word "adjuvare" which means "help" in English to enhance the immunological responses when given together with antigens. The beginning of adjuvant was mineral oil which enhanced the immune response when it was given with inactivated Salmonella typhimurium. Aluminium salt was used to precipitate diphtheria toxoid and increased level of antibody response was demonstrated when administered with alum-precipitated antigens. Since 1930, aluminium salt has been used as DTaP (diphtheria-tetanus-acellular pertussis vaccine) adjuvant. Many candidates were tested for adjuvant activity but only aluminum salt is allowed to use for human vaccines. New adjuvant MF59, oil-in-water emulsion type, was developed for influenza vaccine for elderly (Fluad) and series of AS adjuvant are used for hepatitis B, pandemic flue, and human papiloma virus vaccines. Oil-adjuvanted influenza pandemic vaccines induced higher antibody response than alum-adjuvanted vaccine with higher incidence of adverse events, especially for local reactions. Alum-adjuvanted whole virion inactivated H5N1 vaccine was developed in Japan, and it induced relatively well immune responses in adults. When it applied for children, febrile reaction was noted in approximately 60% of the subjects, with higher antibodies. Recent investigation on innate immunity demonstrates that adjuvant activity is initiated from the stimulation on innate immunity and/or inflammasome, resulting in cytokine induction and antigen uptake by monocytes and macrophages. The probable reason for high incidence of febrile reaction should be investigated to develop a safe and effective influenza vaccine.

  6. Safety, immunogenicity, and lot-to-lot consistency of a split-virion quadrivalent influenza vaccine in younger and older adults: A phase III randomized, double-blind clinical trial.

    Science.gov (United States)

    Sesay, Sanie; Brzostek, Jerzy; Meyer, Ingo; Donazzolo, Yves; Leroux-Roels, Geert; Rouzier, Régine; Astruc, Béatrice; Szymanski, Henryk; Toursarkissian, Nicole; Vandermeulen, Corinne; Kowalska, Edyta; Van Damme, Pierre; Salamand, Camille; Pepin, Stephanie

    2018-03-04

    Here, we report a randomized multicenter phase III trial assessing the lot-to-lot consistency of the 2014-2015 Northern Hemisphere quadrivalent split-virion inactivated influenza vaccine (IIV4; Sanofi Pasteur) and comparing its immunogenicity and safety with that of trivalent inactivated influenza vaccine (IIV3) in younger and older adults (EudraCT no. 2014-000785-21). Younger (18-60 y, n = 1114) and older (>60 y, n = 1111) adults were randomized 2:2:2:1:1 to receive a single dose of one of three lots of IIV4, the licensed IIV3 containing the B Yamagata lineage strain, or an investigational IIV3 containing the B Victoria lineage strain. Post-vaccination (day 21) hemagglutination inhibition antibody titers were equivalent for the three IIV4 lots. For the pooled IIV4s vs. IIV3, hemagglutination inhibition antibody titers were also non-inferior for the A strains, non-inferior for the B strain when present in the comparator IIV3, and superior for the B strain lineage when absent from the comparator IIV3. For all vaccine strains, seroprotection rates were ≥98% in younger adults and ≥90% in older adults. IIV4 also increased seroneutralizing antibody titers against all three vaccine strains of influenza. All vaccines were well tolerated, with no safety concerns identified. Solicited injection-site reactions were similar for IIV4 and IIV3 and mostly grade 1 and transient. This study showed that in younger and older adults, IIV4 had a similar safety profile as the licensed IIV3 and that including a second B strain lineage in IIV4 provided superior immunogenicity for the added B strain without affecting the immunogenicity of the three IIV3 strains.

  7. Charged-soft-sphere potentials for trivalent metal halides

    International Nuclear Information System (INIS)

    Erbolukbas, A.; Akdeniz, Z.; Tosi, M.P.

    1991-09-01

    Octahedral-type coordination by halogens in the liquid state has been reported for a number of trivalent metal ions from diffraction and Raman scattering experiments on their molten trihalides and from Raman scattering spectroscopy of liquid mixtures of trihalides with alkali halides. We analyze the available data on bond lengths and Raman frequencies by treating an isolated (MX 6 ) 3- species within a model which adopts charged-soft-sphere interionic potentials supplemented by an account of ionic polarization. The trivalent metal ions that we consider are M = La, Ce, Pr, Nd, Sm, Gd, Dy and Y for X = Cl and M = Al for X = F. The main result of the analysis is the prediction of trends in the soft-sphere repulsive parameters for the trivalent metal ions, leading to estimates of all the vibrational frequencies and the binding energy of such octahedral species. (author). 26 refs, 1 fig., 4 tabs

  8. Humoral immune response and delayed type hypersensitivity to influenza vaccine in patients with diabetes mellitus

    NARCIS (Netherlands)

    R.J.A. Diepersloot (Rob); K.P. Bouter (Karel Paul); W.E.Ph. Beyer (Walter); N. Masurel (Nic); J.B. Hoekstra

    1987-01-01

    textabstractThe antibody response and delayed type hypersensitivity reaction to commercially available trivalent influenza vaccine in 159 patients with diabetes mellitus was compared with response and reaction in 28 healthy volunteers. A correction for prevaccination titres was made. No differences

  9. The extraction of some trivalent elements with Aliquat-336

    Energy Technology Data Exchange (ETDEWEB)

    FLandgren, A.; Liljenzin, J.O.; Skalberg, M. [Chalmers Univ. of Technology, Goeteborg (Sweden)

    1995-10-01

    The extraction behaviour of some trivalent elements in the Aliquate-336-1,3-diisopropyl genzene-nitric acid system has been investigated. For most of the elements a maximum in the distribution ratio occur at about 2 molar nitric acid. At 0.20 molar Aliquate-336 lanthanum attained the highest distribution ratio, about 0.05, of all investigated elements. It was found that nitric acid to a large extent influences the distribution ratio of trivalent elements since it competes with metal nitrate complexes for the extractant molecules. A first approach to a model describing the extraction system is derived.

  10. Influenza Vaccination in the Face of Maternal Antibody Results in Enhanced Pneumonia Following Heterologous, Homosubtypic Influenza Challenge

    Science.gov (United States)

    Inactivated influenza vaccines do not provide cross-protection to diverse antigenic strains that could be circulating or suddenly arise in a population. It is desirable to vaccinate at a young age to provide maximum protection from influenza; however, maternally-derived factors (antibody or cells) c...

  11. Principles underlying rational design of live attenuated influenza vaccines

    OpenAIRE

    Jang, Yo Han; Seong, Baik-Lin

    2012-01-01

    Despite recent innovative advances in molecular virology and the developments of vaccines, influenza virus remains a serious burden for human health. Vaccination has been considered a primary countermeasure for prevention of influenza infection. Live attenuated influenza vaccines (LAIVs) are particularly attracting attention as an effective strategy due to several advantages over inactivated vaccines. Cold-adaptation, as a classical means for attenuating viral virulence, has been successfully...

  12. DNA repair in Haemophilus influenzae

    International Nuclear Information System (INIS)

    Bagci, H.

    1979-01-01

    A mutant (hex - ) of Haemophilus influenzae which does not discriminate between low efficiency (LE) and high efficiency (HE) markers has been isolated. The mutant is like wild type in its sensitivity to ultraviolet (UV) radiation, methyl methane sulfonate (MMS), mitomycin C (MC) and nitrous acid (NA). As compared to the wild type, the mutant shows much higher spontaneous as well as bromouracil (BrU)-induced mutation frequencies. Biological inactivation of transforming DNA that had been UV-irradiated or treated with MMS has been studied on the widely used wild type Haemophilus influenzae Rd and several repair deficient mutant strains

  13. Surveillance and vaccine effectiveness of an influenza epidemic predominated by vaccine-mismatched influenza B/Yamagata-lineage viruses in Taiwan, 2011-12 season.

    Directory of Open Access Journals (Sweden)

    Yi-Chun Lo

    Full Text Available INTRODUCTION: The 2011-12 trivalent influenza vaccine contains a strain of influenza B/Victoria-lineage viruses. Despite free provision of influenza vaccine among target populations, an epidemic predominated by influenza B/Yamagata-lineage viruses occurred during the 2011-12 season in Taiwan. We characterized this vaccine-mismatched epidemic and estimated influenza vaccine effectiveness (VE. METHODS: Influenza activity was monitored through sentinel viral surveillance, emergency department (ED and outpatient influenza-like illness (ILI syndromic surveillance, and case-based surveillance of influenza with complications and deaths. VE against laboratory-confirmed influenza was evaluated through a case-control study on ILI patients enrolled into sentinel viral surveillance. Logistic regression was used to estimate VE adjusted for confounding factors. RESULTS: During July 2011-June 2012, influenza B accounted for 2,382 (72.5% of 3,285 influenza-positive respiratory specimens. Of 329 influenza B viral isolates with antigen characterization, 287 (87.2% were B/Yamagata-lineage viruses. Proportions of ED and outpatient visits being ILI-related increased from November 2011 to January 2012. Of 1,704 confirmed cases of influenza with complications, including 154 (9.0% deaths, influenza B accounted for 1,034 (60.7% of the confirmed cases and 103 (66.9% of the deaths. Reporting rates of confirmed influenza with complications and deaths were 73.5 and 6.6 per 1,000,000, respectively, highest among those aged ≥65 years, 50-64 years, 3-6 years, and 0-2 years. Adjusted VE was -31% (95% CI: -80, 4 against all influenza, 54% (95% CI: 3, 78 against influenza A, and -66% (95% CI: -132, -18 against influenza B. CONCLUSIONS: This influenza epidemic in Taiwan was predominated by B/Yamagata-lineage viruses unprotected by the 2011-12 trivalent vaccine. The morbidity and mortality of this vaccine-mismatched epidemic warrants careful consideration of introducing a

  14. Green Tea Catechin-Inactivated Viral Vaccine Platform

    Directory of Open Access Journals (Sweden)

    Yun H. Lee

    2017-12-01

    Full Text Available Traditionally, chemical agents such as formalin (FA and β-propiolactone (BPL have long been used for the preparation of inactivated vaccines or toxoids. It has been shown that FA extensively modifies vaccine antigens and thus affects immunogenicity profiles, sometimes compromising the protective efficacy of the vaccines or even exacerbating the disease upon infection. In this study, we show that natural catechins from green tea extracts (GT can be used as an inactivating agent to prepare inactivated viral vaccines. GT treatment resulted in complete and irreversible inactivation of influenza virus as well as dengue virus. In contrast to FA that reacted extensively with multiple amino acids including lysine, a major anchor residue for epitope binding to MHC molecules, GT catechin epigallocatechin-3-gallate (EGCG crosslinked primarily with cysteine residues and thus preserved the major epitopes of the influenza hemagglutinin. In a mouse model, vaccination with GT-inactivated influenza virus (GTi virus elicited higher levels of viral neutralizing antibodies than FA-inactivated virus (FAi virus. The vaccination completely protected the mice from a lethal challenge and restricted the challenge viral replication in the lungs. Of note, the quality of antibody responses of GTi virus was superior to that with FAi virus, in terms of the magnitude of antibody titer, cross-reactivity to hetero-subtypes of influenza viruses, and the avidity to viral antigens. As the first report of using non-toxic natural compounds for the preparation of inactivated viral vaccines, the present results could be translated into a clinically relevant vaccine platform with improved efficacy, safety, productivity, and public acceptance.

  15. AS03- and MF59-Adjuvanted Influenza Vaccines in Children

    Science.gov (United States)

    Wilkins, Amanda L.; Kazmin, Dmitri; Napolitani, Giorgio; Clutterbuck, Elizabeth A.; Pulendran, Bali; Siegrist, Claire-Anne; Pollard, Andrew J.

    2017-01-01

    Influenza is a major cause of respiratory disease leading to hospitalization in young children. However, seasonal trivalent influenza vaccines (TIVs) have been shown to be ineffective and poorly immunogenic in this population. The development of live-attenuated influenza vaccines and adjuvanted vaccines are important advances in the prevention of influenza in young children. The oil-in-water emulsions MF59 and adjuvant systems 03 (AS03) have been used as adjuvants in both seasonal adjuvanted trivalent influenza vaccines (ATIVs) and pandemic monovalent influenza vaccines. Compared with non-adjuvanted vaccine responses, these vaccines induce a more robust and persistent antibody response for both homologous and heterologous influenza strains in infants and young children. Evidence of a significant improvement in vaccine efficacy with these adjuvanted vaccines resulted in the use of the monovalent (A/H1N1) AS03-adjuvanted vaccine in children in the 2009 influenza pandemic and the licensure of the seasonal MF59 ATIV for children aged 6 months to 2 years in Canada. The mechanism of action of MF59 and AS03 remains unclear. Adjuvants such as MF59 induce proinflammatory cytokines and chemokines, including CXCL10, but independently of type-1 interferon. This proinflammatory response is associated with improved recruitment, activation and maturation of antigen presenting cells at the injection site. In young children MF59 ATIV produced more homogenous and robust transcriptional responses, more similar to adult-like patterns, than did TIV. Early gene signatures characteristic of the innate immune response, which correlated with antibody titers were also identified. Differences were detected when comparing child and adult responses including opposite trends in gene set enrichment at day 3 postvaccination and, unlike adult data, a lack of correlation between magnitude of plasmablast response at day 7 and antibody titers at day 28 in children. These insights show the utility

  16. AS03- and MF59-Adjuvanted Influenza Vaccines in Children

    Directory of Open Access Journals (Sweden)

    Amanda L. Wilkins

    2017-12-01

    Full Text Available Influenza is a major cause of respiratory disease leading to hospitalization in young children. However, seasonal trivalent influenza vaccines (TIVs have been shown to be ineffective and poorly immunogenic in this population. The development of live-attenuated influenza vaccines and adjuvanted vaccines are important advances in the prevention of influenza in young children. The oil-in-water emulsions MF59 and adjuvant systems 03 (AS03 have been used as adjuvants in both seasonal adjuvanted trivalent influenza vaccines (ATIVs and pandemic monovalent influenza vaccines. Compared with non-adjuvanted vaccine responses, these vaccines induce a more robust and persistent antibody response for both homologous and heterologous influenza strains in infants and young children. Evidence of a significant improvement in vaccine efficacy with these adjuvanted vaccines resulted in the use of the monovalent (A/H1N1 AS03-adjuvanted vaccine in children in the 2009 influenza pandemic and the licensure of the seasonal MF59 ATIV for children aged 6 months to 2 years in Canada. The mechanism of action of MF59 and AS03 remains unclear. Adjuvants such as MF59 induce proinflammatory cytokines and chemokines, including CXCL10, but independently of type-1 interferon. This proinflammatory response is associated with improved recruitment, activation and maturation of antigen presenting cells at the injection site. In young children MF59 ATIV produced more homogenous and robust transcriptional responses, more similar to adult-like patterns, than did TIV. Early gene signatures characteristic of the innate immune response, which correlated with antibody titers were also identified. Differences were detected when comparing child and adult responses including opposite trends in gene set enrichment at day 3 postvaccination and, unlike adult data, a lack of correlation between magnitude of plasmablast response at day 7 and antibody titers at day 28 in children. These insights

  17. AS03- and MF59-Adjuvanted Influenza Vaccines in Children.

    Science.gov (United States)

    Wilkins, Amanda L; Kazmin, Dmitri; Napolitani, Giorgio; Clutterbuck, Elizabeth A; Pulendran, Bali; Siegrist, Claire-Anne; Pollard, Andrew J

    2017-01-01

    Influenza is a major cause of respiratory disease leading to hospitalization in young children. However, seasonal trivalent influenza vaccines (TIVs) have been shown to be ineffective and poorly immunogenic in this population. The development of live-attenuated influenza vaccines and adjuvanted vaccines are important advances in the prevention of influenza in young children. The oil-in-water emulsions MF59 and adjuvant systems 03 (AS03) have been used as adjuvants in both seasonal adjuvanted trivalent influenza vaccines (ATIVs) and pandemic monovalent influenza vaccines. Compared with non-adjuvanted vaccine responses, these vaccines induce a more robust and persistent antibody response for both homologous and heterologous influenza strains in infants and young children. Evidence of a significant improvement in vaccine efficacy with these adjuvanted vaccines resulted in the use of the monovalent (A/H1N1) AS03-adjuvanted vaccine in children in the 2009 influenza pandemic and the licensure of the seasonal MF59 ATIV for children aged 6 months to 2 years in Canada. The mechanism of action of MF59 and AS03 remains unclear. Adjuvants such as MF59 induce proinflammatory cytokines and chemokines, including CXCL10, but independently of type-1 interferon. This proinflammatory response is associated with improved recruitment, activation and maturation of antigen presenting cells at the injection site. In young children MF59 ATIV produced more homogenous and robust transcriptional responses, more similar to adult-like patterns, than did TIV. Early gene signatures characteristic of the innate immune response, which correlated with antibody titers were also identified. Differences were detected when comparing child and adult responses including opposite trends in gene set enrichment at day 3 postvaccination and, unlike adult data, a lack of correlation between magnitude of plasmablast response at day 7 and antibody titers at day 28 in children. These insights show the utility

  18. Characterization of influenza vaccine immunogenicity using influenza antigen microarrays.

    Directory of Open Access Journals (Sweden)

    Jordan V Price

    Full Text Available Existing methods to measure influenza vaccine immunogenicity prohibit detailed analysis of epitope determinants recognized by immunoglobulins. The development of highly multiplex proteomics platforms capable of capturing a high level of antibody binding information will enable researchers and clinicians to generate rapid and meaningful readouts of influenza-specific antibody reactivity.We developed influenza hemagglutinin (HA whole-protein and peptide microarrays and validated that the arrays allow detection of specific antibody reactivity across a broad dynamic range using commercially available antibodies targeted to linear and conformational HA epitopes. We derived serum from blood draws taken from 76 young and elderly subjects immediately before and 28±7 days post-vaccination with the 2008/2009 trivalent influenza vaccine and determined the antibody reactivity of these sera to influenza array antigens.Using linear regression and correcting for multiple hypothesis testing by the Benjamini and Hochberg method of permutations over 1000 resamplings, we identified antibody reactivity to influenza whole-protein and peptide array features that correlated significantly with age, H1N1, and B-strain post-vaccine titer as assessed through a standard microneutralization assay (p<0.05, q <0.2. Notably, we identified several peptide epitopes that were inversely correlated with regard to age and seasonal H1N1 and B-strain neutralization titer (p<0.05, q <0.2, implicating reactivity to these epitopes in age-related defects in response to H1N1 influenza. We also employed multivariate linear regression with cross-validation to build models based on age and pre-vaccine peptide reactivity that predicted vaccine-induced neutralization of seasonal H1N1 and H3N2 influenza strains with a high level of accuracy (84.7% and 74.0%, respectively.Our methods provide powerful tools for rapid and accurate measurement of broad antibody-based immune responses to influenza

  19. Effectiveness of 2010/2011 seasonal influenza vaccine in Ireland.

    LENUS (Irish Health Repository)

    Barret, A S

    2012-02-01

    We conducted a case-control study to estimate the 2010\\/2011 trivalent influenza vaccine effectiveness (TIVE) using the Irish general practitioners\\' influenza sentinel surveillance scheme. Cases were influenza-like illness (ILI) patients with laboratory-confirmed influenza. Controls were ILI patients who tested negative for influenza. Participating sentinel general practitioners (GP) collected swabs from patients presenting with ILI along with their vaccination history and other individual characteristics. The TIVE was computed as (1 - odds ratiofor vaccination) x100%. Of 60 sentinel GP practices, 22 expressed interest in participating in the study and 17 (28%) recruited at least one ILI patient. In the analysis, we included 106 cases and 85 controls. Seven controls (8.2%) and one influenza case (0.9%) had been vaccinated in 2010\\/2011. The estimated TIVE against any influenza subtype was 89.4% [95% CI: 13.8; 99.8%], suggesting a protective effect against GP-attended laboratory confirmed influenza. This study design could be used to monitor influenza vaccine effectiveness annually but sample size and vaccination coverage should be increased to obtain precise and adjusted estimates.

  20. Parental attitudes towards influenza vaccination for children in South India.

    Science.gov (United States)

    Ramprasad, Chethan; Zachariah, Rajeev; Steinhoff, Mark; Simon, Anna

    2017-02-01

    The rate of influenza vaccination is low for children in India. The purpose of this study is to assess parental attitudes towards influenza vaccination in South India. Participants were parents who brought their children to the Well Baby Clinic of Christian Medical College Hospital, Vellore, India for routine immunization. Participants answered questions by written survey while waiting for their children's vaccination. A total of 456 surveys were completed (403 parents did not opt for trivalent influenza vaccination and 53 opted for influenza vaccination). The majority (53.60%) of those parents who did not accept influenza vaccination identified the lack of a doctor's recommendation as the main reason. When asked separately, many non-acceptors (44.91%) indicated that they did not believe or were not sure that the influenza vaccine was effective. Nearly all non-acceptors (92.56%) stated that they would opt for influenza vaccination if a doctor recommended it. The most common reason that parents not opting for influenza vaccination for their children was the lack of recommendation by a doctor. The results of this study suggest that recommendation by a doctor is a more important factor than belief in efficacy, cost, or convenience in parental decision-making regarding childhood influenza vaccination in India, unlike the United States where parents are less likely to follow recommendations.

  1. Electro-deposition behaviors of trivalent chromium during pulse plating

    Science.gov (United States)

    Choi, Yong

    2010-10-01

    Thick trivalent chromium layers were prepared in a modified chromium sulfate bath by pulse plating to replace hexavalent hard chromium coating in industrial fields; layer microstructure development was systematically studied by using electron microscopy and small angle neutron scattering (SANS) to give a model for nucleation and growth behaviors during the pulse plating. Finer columnar grain was formed by pulse plating due to its high nucleation rate at the same current density. Average deposition rate of the trivalent chromium layers is in the range of 32.4 μm/h to 49.7 μm/h. The deposition rate increases as the diameter of cylindrical shape of chromium cluster in a columnar grain is reduced. The highest deposition rate in this study was observed under the conditions of direct current density of 0.4 Acm-2, combined with a rectangular shape pulse current density of 1.5 Acm-2 with a 10/2 on-off time ratio. Most of the inner-cracks of the trivalent chromium layers have dimensions in the range of about 39 nm. Ultrasonic agitation during pulse plating resulted in an increase of neutral salt fog spray life, which is related to smaller crack size and broader size distribution in the trivalent chromium.

  2. Serum IgM levels independently predict immune response to influenza vaccine in long-term survivors vaccinated at >1 year after undergoing allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    Fukatsu, Yusuke; Nagata, Yasuyuki; Adachi, Miwa; Yagyu, Tomohiro; Ono, Takaaki

    2017-05-01

    Influenza virus infection can cause fatal complications (e.g., pneumonia) in immunodeficient long-term survivors of allogeneic hematopoietic stem cell transplantation (allo-HSCT). The immune response to the vaccine improves if it is administered at >1 year after allo-HSCT, although the response may vary according to the patient's immune status. We sought to identify predictors of immune response to trivalent inactivated influenza vaccine (TIV) among patients vaccinated at >1 year after allo-HSCT. We included 27 allo-HSCT recipients, with a median interval of 4.3 years (range 1.0-10.1 years) from transplantation to vaccination. Nineteen patients achieved a response to TIV, although a low immune response to TIV was significantly associated with calcineurin inhibitor treatment, and moderate chronic graft-versus-host disease and IgM levels of immune response to TIV. These results indicate that a more effective approach is needed to induce a vaccine-specific immune response among long-term survivors of allo-HSCT who have low serum IgM levels.

  3. Priming by a novel universal influenza vaccine (Multimeric-001)-a gateway for improving immune response in the elderly population.

    Science.gov (United States)

    Atsmon, Jacob; Caraco, Yoseph; Ziv-Sefer, Sagit; Shaikevich, Dimitry; Abramov, Ester; Volokhov, Inna; Bruzil, Svetlana; Haima, Kirsten Y; Gottlieb, Tanya; Ben-Yedidia, Tamar

    2014-10-07

    A new vaccine, "Multimeric-001" (M-001) has been recently developed, containing conserved, common linear influenza epitopes that activate both cellular and humoral arms of the immune system against a wide variety of influenza A and B strains. Apart from its direct action, M-001 is an attractive candidate for priming immune responses to seasonal influenza vaccine for the elderly population. The current clinical study was designed to assess M-001's standalone and priming action in participants over 65 years old. Evaluation of standalone action is based on induction of cell mediated immunity (CMI), since M-001 alone does not induce hemagglutinin inhibition (HAI) antibodies. This was a two-center, randomized, placebo-controlled study. 120 participants were randomized 1:1:1:1 into four groups to receive either two sequential non-adjuvanted or a single non-adjuvanted or a single adjuvanted intramuscular injection of 500 mcg M-001 (treatment), or one placebo (saline) injection, before receiving the trivalent inactivated influenza vaccine (TIV). Due to visual differences between placebo and treatment the study was partially blinded. HAI was evaluated at baseline and 3 weeks after standard TIV vaccination as a measure of M-001's efficacy. CMI responses were evaluated in a subset (10/group) of the participants. Participants were monitored for safety throughout the study. Overall the treatment was well-tolerated and safe, though sample sizes allowed only limited statistical analysis. M-001 priming resulted in enhanced seroconversion towards all three TIV strains, compared to priming with placebo. Significant elevation of influenza-specific CMI was observed following immunization with M-001 alone. The standalone and priming actions of M-001 were demonstrated in elderly participants despite the limitations of small population size and pre-existing HAI antibody titers in some participants. As a standalone vaccine, M-001 induced significant CMI to multiple strains and as a primer

  4. Influenza vaccine effectiveness in adults 65 years and older, Denmark, 2015/16

    DEFF Research Database (Denmark)

    Emborg, H.; Krause, T. G.; Nielsen, L.

    2016-01-01

    In Denmark, both influenza A(H1N1)pdm09 and influenza B co-circulated in the 2015/16 season. We estimated the vaccine effectiveness (VE) of the trivalent influenza vaccine in patients 65 years and older using the test-negative case-control design. The adjusted VE against influenza A(H1N1)pdm09...... was 35.0% (95% confidence interval (CI): 11.1-52.4) and against influenza B 4.1% (95% CI: -22.0 to 24.7). The majority of influenza A(H1N1)pdm09 circulating in 2015/16 belonged to the new genetic subgroup subclade 6B.1....

  5. Incidence of influenza virus infections in children in Hong Kong in a 3-year randomized placebo-controlled vaccine study, 2009-2012.

    Science.gov (United States)

    Cowling, Benjamin J; Perera, Ranawaka A P M; Fang, Vicky J; Chan, Kwok-Hung; Wai, Winnie; So, Hau Chi; Chu, Daniel K W; Wong, Jessica Y; Shiu, Eunice Y; Ng, Sophia; Ip, Dennis K M; Peiris, J S Malik; Leung, Gabriel M

    2014-08-15

    School-aged children suffer high rates of influenza virus infections and associated illnesses each year, and are a major source of transmission in the community. However, information on the cumulative incidence of infection in specific epidemics is scarce, and there are limited studies with sufficient follow-up to identify the strength and duration of protection against reinfection. We randomly allocated children 5-17 years of age to receive trivalent inactivated influenza vaccine (TIV) or placebo from September 2009 through January 2010, and then conducted follow-up for 3 years including regular collection of sera, symptom diaries, and collection of nose and throat swabs during illness episodes in participants or their household members. Of 796 children initially randomized, 484 continued to participate for all 3 years. In unvaccinated children, cumulative incidence of infection was estimated to be 59% in the first wave of H1N1pdm09 in 2009-2010, and 7%, 14%, 20%, and 31% in subsequent epidemics of H3N2 (2010), H1N1pdm09 (2011), B (2012), and H3N2 (2012), respectively. Infection with H1N1pdm09 in 2009-2010 and H3N2 in 2010 was associated with protection against infection with subsequent epidemics of the same subtype in 2011 and 2012, respectively, but we found no evidence of heterotypic or heterosubtypic protection against infection. We identified substantial incidence of influenza virus infections in children in Hong Kong in 5 major epidemics over a 3-year period, and evidence of homosubtypic but not heterosubtypic protection following infection. NCT00792051. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  6. Inactivation Data.xlsx

    Data.gov (United States)

    U.S. Environmental Protection Agency — The data set is a spreadsheet that contains results of inactivation experiments that were conducted to to determine the effectiveness of chlorine in inactivating B....

  7. Meningitis - H. influenzae

    Science.gov (United States)

    H. influenzae meningitis; H. flu meningitis; Haemophilus influenzae type b meningitis ... H. influenzae meningitis is caused by Haemophilus influenzae type b bacteria. This illness is not the same as the flu ( influenza ), ...

  8. Kaempferol ameliorates H9N2 swine influenza virus-induced acute lung injury by inactivation of TLR4/MyD88-mediated NF-κB and MAPK signaling pathways.

    Science.gov (United States)

    Zhang, Ruihua; Ai, Xia; Duan, Yongjie; Xue, Man; He, Wenxiao; Wang, Cunlian; Xu, Tong; Xu, Mingju; Liu, Baojian; Li, Chunhong; Wang, Zhijun; Zhang, Ruihong; Wang, Guohua; Tian, Shufei; Liu, Huifeng

    2017-05-01

    Kaempferol, a very common type of dietary flavonoids, has been found to exert antioxidative and anti-inflammatory properties. The purpose of our investigation was designed to reveal the effect of kaempferol on H9N2 influenza virus-induced inflammation in vivo and in vitro. In vivo, BALB/C mice were infected intranasally with H9N2 influenza virus with or without kaempferol treatment to induce acute lung injury (ALI) model. In vitro, MH-S cells were infected with H9N2 influenza virus with or without kaempferol treatment. In vivo, kaempferol treatment attenuated pulmonary edema, the W/D mass ratio, pulmonary capillary permeability, myeloperoxidase (MPO) activity, and the numbers of inflammatory cells. Kaempferol reduced ROS and Malondialdehyde (MDA) production, and increased the superoxide dismutase (SOD) activity. Kaempferol also reduced overproduction of TNF-α, IL-1β and IL-6. In addition, kaempferol decreased the H9N2 viral titre. In vitro, ROS, MDA, TNF-α, IL-1β and IL-6 was also reduced by kaempferol. Moreover, our data showed that kaempferol significantly inhibited the upregulation of toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), phosphorylation level of IκBα and nuclear factor-κB (NF-κB) p65, NF-κB p65 DNA binding activity, and phosphorylation level of MAPKs, both in vivo and in vitro. These results suggest that kaempferol exhibits a protective effect on H9N2 virus-induced inflammation via suppression of TLR4/MyD88-mediated NF-κB and MAPKs pathways, and kaempferol may be considered as an effective drug for the potential treatment of influenza virus-induced ALI. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  9. Inactivation of Caliciviruses

    Directory of Open Access Journals (Sweden)

    Raymond Nims

    2013-03-01

    Full Text Available The Caliciviridae family of viruses contains clinically important human and animal pathogens, as well as vesivirus 2117, a known contaminant of biopharmaceutical manufacturing processes employing Chinese hamster cells. An extensive literature exists for inactivation of various animal caliciviruses, especially feline calicivirus and murine norovirus. The caliciviruses are susceptible to wet heat inactivation at temperatures in excess of 60 °C with contact times of 30 min or greater, to UV-C inactivation at fluence ≥30 mJ/cm2, to high pressure processing >200 MPa for >5 min at 4 °C, and to certain photodynamic inactivation approaches. The enteric caliciviruses (e.g.; noroviruses display resistance to inactivation by low pH, while the non-enteric species (e.g.; feline calicivirus are much more susceptible. The caliciviruses are inactivated by a variety of chemicals, including alcohols, oxidizing agents, aldehydes, and β-propiolactone. As with inactivation of viruses in general, inactivation of caliciviruses by the various approaches may be matrix-, temperature-, and/or contact time-dependent. The susceptibilities of the caliciviruses to the various physical and chemical inactivation approaches are generally similar to those displayed by other small, non-enveloped viruses, with the exception that the parvoviruses and circoviruses may require higher temperatures for inactivation, while these families appear to be more susceptible to UV-C inactivation than are the caliciviruses.

  10. Impact of Haemophilus influenzae type B (Hib) and viral influenza vaccinations in pregnancy for improving maternal, neonatal and infant health outcomes.

    Science.gov (United States)

    Salam, Rehana A; Das, Jai K; Dojo Soeandy, Chesarahmia; Lassi, Zohra S; Bhutta, Zulfiqar A

    2015-06-09

    ), intubation (RR 1.03, 95% CI 0.55 to 1.95, one study, 213 infants) and neonatal jaundice (RR 1.01, 95% CI 0.52 to 1.97, one study, 213 infants). We could not grade the evidence for quality due to lack of outcome data. Viral influenza vaccination during pregnancy versus placeboOne trial involving 2116 women and 2049 infants evaluating the impact of trivalent inactivated influenza vaccine (IIV3) during pregnancy was included under this comparison.There was no clear difference between the viral influenza and placebo control group in terms of most of this review's primary outcomes: maternal death (RR 4.96, 95% CI 0.24 to 103.24, moderate quality evidence), infant death up to 175 days after birth (RR 0.71, 95% CI 0.37 to 1.37, moderate quality evidence), perinatal death (stillbirth and death in the first week of life) (RR 1.32, 95% CI 0.73 to 2.38, moderate quality evidence), influenza-like illness in women (RR 0.96, 95% CI 0.79 to 1.16) or their babies (RR 1.02, 95% CI 0.94 to 1.09), any respiratory illness in women (RR 0.97, 95% CI 0.91 to 1.04, high quality evidence) or their babies (RR 1.01, 95% CI 0.95 to 1.07, high quality evidence). There were also no clear differences between vaccination and placebo control groups in terms of maternal hospitalisation for any infection (RR 2.27, 95% CI 0.94 to 5.49; 2116 women, moderate quality evidence), and neonatal hospitalisation for sepsis (RR 1.60, 95% CI 0.73 to 3.50; 2049 infants, moderate quality evidence). However, viral influenza vaccination during pregnancy was associated with a reduction in reverse-transcriptase-polymerase-chain-reaction (RT-PCR) confirmed influenza among infants (RR 0.51, 95% CI 0.30 to 0.88, one study, 2049 infants) and women (RR 0.50, 95% CI 0.29 to 0.86, one study, 2116 women).In terms of this review's secondary outcomes, there were no clear differences in terms of the impact on pregnancy outcomes (miscarriage, preterm labour and stillbirth), hospitalisation for respiratory infection among women and infants

  11. Advancing the scientific basis of trivalent actinide-lanthanide separations

    Energy Technology Data Exchange (ETDEWEB)

    Nash, K.L. [Washington State University, Department of Chemistry, PO Box 644630, Pullman, WA 99164-4630 (United States)

    2013-07-01

    For advanced fuel cycles designed to support transmutation of transplutonium actinides, several options have been demonstrated for process-scale aqueous separations for U, Np, Pu management and for partitioning of trivalent actinides and fission product lanthanides away from other fission products. The more difficult mutual separation of Am/Cm from La-Tb remains the subject of considerable fundamental and applied research. The chemical separations literature teaches that the most productive alternatives to pursue are those based on ligand donor atoms less electronegative than O, specifically N- and S-containing complexants and chloride ion (Cl{sup -}). These 'soft-donor' atoms have exhibited usable selectivity in their bonding interactions with trivalent actinides relative to lanthanides. In this report, selected features of soft donor reagent design, characterization and application development will be discussed. The roles of thiocyanate, aminopoly-carboxylic acids and lactate in separation processes are detailed. (authors)

  12. Trivalent Cation Induced Bundle Formation of Filamentous fd Phages.

    Science.gov (United States)

    Korkmaz Zirpel, Nuriye; Park, Eun Jin

    2015-09-01

    Bacteriophages are filamentous polyelectrolyte viral rods infecting only bacteria. In this study, we investigate the bundle formation of fd phages with trivalent cations having different ionic radii (Al(3+) , La(3+) and Y(3+) ) at various phage and counterion concentrations, and at varying bundling times. Aggregated phage bundles were detected at relatively low trivalent counterion concentrations (1 mM). Although 10 mM and 100 mM Y(3+) and La(3+) treatments formed larger and more intertwined phage bundles, Al(3+) and Fe(3+) treatments lead to the formation of networking filaments. Energy dispersive X-ray spectroscopy (EDX) analyses confirmed the presence of C, N and O peaks on densely packed phage bundles. Immunofluorescence labelling and ELISA analyses with anti-p8 antibodies showed the presence of phage filaments after bundling. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Advancing the scientific basis of trivalent actinide-lanthanide separations

    International Nuclear Information System (INIS)

    Nash, K.L.

    2013-01-01

    For advanced fuel cycles designed to support transmutation of transplutonium actinides, several options have been demonstrated for process-scale aqueous separations for U, Np, Pu management and for partitioning of trivalent actinides and fission product lanthanides away from other fission products. The more difficult mutual separation of Am/Cm from La-Tb remains the subject of considerable fundamental and applied research. The chemical separations literature teaches that the most productive alternatives to pursue are those based on ligand donor atoms less electronegative than O, specifically N- and S-containing complexants and chloride ion (Cl - ). These 'soft-donor' atoms have exhibited usable selectivity in their bonding interactions with trivalent actinides relative to lanthanides. In this report, selected features of soft donor reagent design, characterization and application development will be discussed. The roles of thiocyanate, aminopoly-carboxylic acids and lactate in separation processes are detailed. (authors)

  14. Study on thermostabilizers for trivalent oral poliomyelitis vaccine

    Directory of Open Access Journals (Sweden)

    M. L. F. Leal

    1990-09-01

    Full Text Available Different formulations of trivalent oral poliomyelitis vaccine were tested, in order to obtain better thermostability, reduce corrosion of machinery and improve production costs. Magnesium chloride, sucrose, arginine and 199-Hank's medium were used in the formulations. The most appropriate formulation was a mixture of MgCl2 and arginine, which was highly thermostable, and had low production costs. The low corrosive formulation was rejected, due to low thermostability on storage.

  15. PREFERENTIAL SEGREGATION OF CHROMOSOMES FROM A TRIVALENT IN HAPLOPAPPUS GRACILIS.

    Science.gov (United States)

    JACKSON, R C

    1964-07-31

    Crosses between plants of Haplopappus gracilis (n = 2) and a race with three pairs of chromosomes (tribivalens) gave a highly fertile five-chromosome hybrid. In both races the chromosomes with the satellites appear homologous, but the other two tribivalens chromosomes pair with the A chromosome (without a satellite) of H. gracilis. Disjunction from the resulting trivalent is preferential: the A chromosome goes to one pole and the two tribivalens chromosomes to the other.

  16. Traditional and New Influenza Vaccines

    Science.gov (United States)

    Wong, Sook-San

    2013-01-01

    SUMMARY The challenges in successful vaccination against influenza using conventional approaches lie in their variable efficacy in different age populations, the antigenic variability of the circulating virus, and the production and manufacturing limitations to ensure safe, timely, and adequate supply of vaccine. The conventional influenza vaccine platform is based on stimulating immunity against the major neutralizing antibody target, hemagglutinin (HA), by virus attenuation or inactivation. Improvements to this conventional system have focused primarily on improving production and immunogenicity. Cell culture, reverse genetics, and baculovirus expression technology allow for safe and scalable production, while adjuvants, dose variation, and alternate routes of delivery aim to improve vaccine immunogenicity. Fundamentally different approaches that are currently under development hope to signal new generations of influenza vaccines. Such approaches target nonvariable regions of antigenic proteins, with the idea of stimulating cross-protective antibodies and thus creating a “universal” influenza vaccine. While such approaches have obvious benefits, there are many hurdles yet to clear. Here, we discuss the process and challenges of the current influenza vaccine platform as well as new approaches that are being investigated based on the same antigenic target and newer technologies based on different antigenic targets. PMID:23824369

  17. Efficacy of a Trivalent Hand, Foot, and Mouth Disease Vaccine against Enterovirus 71 and Coxsackieviruses A16 and A6 in Mice.

    Science.gov (United States)

    Caine, Elizabeth A; Fuchs, Jeremy; Das, Subash C; Partidos, Charalambos D; Osorio, Jorge E

    2015-11-17

    Hand, foot, and mouth disease (HFMD) has recently emerged as a major public health concern across the Asian-Pacific region. Enterovirus 71 (EV71) and Coxsackievirus A16 (CVA16) are the primary causative agents of HFMD, but other members of the Enterovirus A species, including Coxsackievirus A6 (CVA6), can cause disease. The lack of small animal models for these viruses have hampered the development of a licensed HFMD vaccine or antivirals. We have previously reported on the development of a mouse model for EV71 and demonstrated the protective efficacy of an inactivated EV71 vaccine candidate. Here, mouse-adapted strains of CVA16 and CVA6 were produced by sequential passage of the viruses through mice deficient in interferon (IFN) α/β (A129) and α/β and γ (AG129) receptors. Adapted viruses were capable of infecting 3 week-old A129 (CVA6) and 12 week-old AG129 (CVA16) mice. Accordingly, these models were used in active and passive immunization studies to test the efficacy of a trivalent vaccine candidate containing inactivated EV71, CVA16, and CVA6. Full protection from lethal challenge against EV71 and CVA16 was observed in trivalent vaccinated groups. In contrast, monovalent vaccinated groups with non-homologous challenges failed to cross protect. Protection from CVA6 challenge was accomplished through a passive transfer study involving serum raised against the trivalent vaccine. These animal models will be useful for future studies on HFMD related pathogenesis and the efficacy of vaccine candidates.

  18. Efficacy of a Trivalent Hand, Foot, and Mouth Disease Vaccine against Enterovirus 71 and Coxsackieviruses A16 and A6 in Mice

    Directory of Open Access Journals (Sweden)

    Elizabeth A. Caine

    2015-11-01

    Full Text Available Hand, foot, and mouth disease (HFMD has recently emerged as a major public health concern across the Asian-Pacific region. Enterovirus 71 (EV71 and Coxsackievirus A16 (CVA16 are the primary causative agents of HFMD, but other members of the Enterovirus A species, including Coxsackievirus A6 (CVA6, can cause disease. The lack of small animal models for these viruses have hampered the development of a licensed HFMD vaccine or antivirals. We have previously reported on the development of a mouse model for EV71 and demonstrated the protective efficacy of an inactivated EV71 vaccine candidate. Here, mouse-adapted strains of CVA16 and CVA6 were produced by sequential passage of the viruses through mice deficient in interferon (IFN α/β (A129 and α/β and γ (AG129 receptors. Adapted viruses were capable of infecting 3 week-old A129 (CVA6 and 12 week-old AG129 (CVA16 mice. Accordingly, these models were used in active and passive immunization studies to test the efficacy of a trivalent vaccine candidate containing inactivated EV71, CVA16, and CVA6. Full protection from lethal challenge against EV71 and CVA16 was observed in trivalent vaccinated groups. In contrast, monovalent vaccinated groups with non-homologous challenges failed to cross protect. Protection from CVA6 challenge was accomplished through a passive transfer study involving serum raised against the trivalent vaccine. These animal models will be useful for future studies on HFMD related pathogenesis and the efficacy of vaccine candidates.

  19. Cold-adapted live attenuated influenza vaccines developed in Russia: Can they contribute to meeting the needs for influenza control in other countries?

    International Nuclear Information System (INIS)

    Kendal, Alan P.

    1997-01-01

    It is now more than 30 years since the first cold-adapted influenza viruses were developed in Russia as potential live, attenuated vaccines. In the past 15-20 years considerable experience has been gained from Russian and joint Russian-US laboratory and clinical studies with type A monovalent and bivalent vaccines prepared with genetic reassortant viruses derived from one of these cold-adapted viruses in particular, A/Leningrad/134/57. More recent experiences include use of trivalent cold-adapted vaccines with a type B component. The overall high level of safety of individual and combined vaccines in pre-school and school-aged children, with illness reductions in open field trials equivalent to that seen with inactivated vaccines, is such as to suggest that practical measures might now be justified to facilitate expansion of the use of these vaccines to other countries. It is proposed that further experimentation with the Russian cold-adapted live attenuated vaccines should be focused on issues that will relate to the public health perspective, i.e. selection of the single best candidate type A and B vaccines for intense study using as criteria their potential for meeting licensing requirements outside Russia, and documenting the clinical protective efficacy of a single vaccine dose compared to two doses as studied until now. Resolution of these issues is important to ensure that costs for future live vaccine production, control, and utilization will be kept at lowest levels so that expanded use of live vaccines will have maximum cost-benefit and affordability. To guide those interested in these issues, examples are given of populations for whom a licensed live cold-adapted vaccine might be considered, together with indications of extra data needed to fully validate each suggested use

  20. Influenza vaccine effectiveness in adults 65 years and older, Denmark, 2015/16 - a rapid epidemiological and virological assessment

    DEFF Research Database (Denmark)

    Emborg, Hanne Dorthe; Krause, Tyra Grove; Nielsen, Lene

    2016-01-01

    In Denmark, both influenza A(H1N1)pdm09 and influenza B co-circulated in the 2015/16 season. We estimated the vaccine effectiveness (VE) of the trivalent influenza vaccine in patients 65 years and older using the test-negative case-control design. The adjusted VE against influenza A(H1N1)pdm09...... was 35.0% (95% confidence interval (CI): 11.1-52.4) and against influenza B 4.1% (95% CI: -22.0 to 24.7). The majority of influenza A(H1N1)pdm09 circulating in 2015/16 belonged to the new genetic subgroup subclade 6B.1....

  1. An Adjuvant for the Induction of Potent, Protective Humoral Responses to an H5N1 Influenza Virus Vaccine with Antigen-Sparing Effect in Mice ▿ †

    OpenAIRE

    Lau, Yuk-Fai; Tang, Lay-Hoon; McCall, Amber W.; Ooi, Eng-Eong; Subbarao, Kanta

    2010-01-01

    Intramuscular administration of inactivated influenza virus vaccine is the main vaccine platform used for the prevention of seasonal influenza virus infection. In clinical trials, inactivated H5N1 vaccines have been shown to be safe and capable of eliciting immune correlates of protection. However, the H5N1 vaccines are poorly immunogenic compared to seasonal influenza virus vaccines. Needle-free vaccination would be more efficient and economical in a pandemic, and the development of an effec...

  2. Prevención y control de la influenza

    Directory of Open Access Journals (Sweden)

    2002-01-01

    Full Text Available This piece summarizes a report that updates the recommendations of the Advisory Committee on Immunization Practices of the United States of America with regard to the use of the influenza vaccine and of specific antiviral agents for influenza. The recommended 2002-2003 trivalent vaccine virus strains are A/Moscow/10/99 (H3N2-like, A/New Caledonia/20/99 (H1N1-like, and B/Hong Kong/330/2001-like. The piece defines the groups who should be vaccinated and the persons who should not be, as well as adverse reactions to the vaccine. Influenza antivirals are a complement to--but not a replacement for--the vaccine in preventing and controlling the disease. The piece also analyzes for the antiviral agents the indications for their use, dosage, routes of administration, pharmacokinetic characteristics, interactions, and side effects.

  3. Influenza virus vaccine live intranasal--MedImmune vaccines: CAIV-T, influenza vaccine live intranasal.

    Science.gov (United States)

    2003-01-01

    that it should be able to provide these data without conducting further clinical trials. In January 2002, Aviron submitted additional clinical and manufacturing data on FluMist to the US FDA. MedImmune received a second Complete Response Letter from the US FDA on 10 July 2002, requesting clarification and additional data relating to previously submitted information. One of the most significant issues raised by the US FDA was the exacerbated rate of asthma and wheezing in 18-35-month-old patients using FluMist. MedImmune is considering two options to address this issue; to either exclude patients with asthma and wheezing from the label, or to exclude 18- to 30-month-old patients from the proposed indication. On 26 August 2002, MedImmune reported that it had completed the submission of information requested by the US FDA for FluMist. On 17 December 2002, the US FDA's Vaccination and Related Biologicals Products Advisory Committee (VRBPAC) recommended that the FDA approve FluMist to prevent influenza in healthy children, adolescents and adults (ages 5-49 years). Even though the VRBPAC voted in favour of the product's safety in the 50- to 64-year age group, they believed that the data set on efficacy for this age group was insufficient. The committee has also recommended that head-to-head studies should be conducted comparing FluMist to the marketed trivalent inactivated vaccine. Additional clinical trials suggested by the VRBPAC were shedding studies to more clearly define the probability of transmitting the influenza vaccine virus to a high-risk patient and annual revaccination studies. On 30 January 2003, MedImmune announced that it had received a Complete Response Letter from the US FDA requesting clarification and additional information relating to data previously submitted. No additional clinical trials were requested. The company responded to the five questions contained in the letter on 7 February 2003. (ABSTRACT TRUNCATED)

  4. 76 FR 79203 - Prospective Grant of Exclusive License: Avian Influenza Vaccines for Domesticated Poultry/Wild...

    Science.gov (United States)

    2011-12-21

    ... Veterinary Influenza Vaccines. Sustained outbreaks of highly pathogenic influenza in animals increase the... advantages: (a) More efficient and versatile than the conventional inactivated whole-virus vaccines; (b) Can... vaccinated animals to be differentiated from naturally infected animals, key if governments mandate...

  5. Immunogenicity and safety of an AS03-adjuvanted H5N1 pandemic influenza vaccine in Korean adults: a phase IV, randomized, open-label, controlled study.

    Science.gov (United States)

    Izurieta, Patricia; Kim, Woo Joo; Wie, Seong-Heon; Lee, Jacob; Lee, Jin-Soo; Dramé, Mamadou; Vaughn, David W; Schuind, Anne

    2015-06-04

    AS03-adjuvanted H5N1 pandemic influenza vaccines have been assessed in an extensive clinical development program conducted in North America, Europe, and Asia including children from 6 months of age, adults, and elderly adults. We evaluated AS03-H5N1 in Korean adults 18 through 60 years of age. This Phase IV, randomized, study was conducted to assess the immunogenicity, reactogenicity, and safety of two doses (3.75μg of hemagglutinin antigen) of A/Indonesia/5/2005 (H5N1) adjuvanted with AS03 given 21 days apart in Korean adults. Antibody responses were assessed using hemagglutination-inhibition (HI) assays against the vaccine strain and a vaccine-heterologous strain (A/Vietnam/1194/2004) 21 days after the second dose. A control group (safety) received a licensed seasonal inactivated trivalent influenza vaccine (TIV). Reactogenicity was assessed for 7 days after each vaccination, and unsolicited adverse events were assessed for 182 days following vaccination in both study groups (NCT01730378). AS03-H5N1 was immunogenic and elicited robust HI antibody responses with seroconversion rates of 100% for the vaccine strain and 69.1% for the heterologous strain (N=81). HI antibody responses fulfilled the European licensure criteria for immunogenicity (primary endpoint). The incidence of local and systemic solicited adverse events (reactogenicity) was higher with AS03-H5N1 than TIV. There was no apparent difference in the rate of unsolicited adverse events in the AS03-H5N1 and TIV groups. The results indicate that AS03-H5N1 vaccine is immunogenic with reactogenicity and safety findings that are consistent with the established profile of AS03-H5N1 vaccine. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  6. Squeezing clathrate cages to host trivalent rare-earth guests

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jian [Iowa State Univ., Ames, IA (United States). Department of Chemistry; Ames Lab., Ames, IA (United States); He, Yuping [Sandia National Lab. (SNL-CA), Livermore, CA (United States); Mordvinova, Natalia E. [Laboratoire CRISMAT, ENSICAEN, CNRS UMR (France); Lebedev, Oleg [Laboratoire CRISMAT, ENSICAEN, CNRS UMR (France); Kovnir, Kirill [Iowa State Univ., Ames, IA (United States). Department of Chemistry; Ames Lab., Ames, IA (United States)

    2017-11-01

    Strike difference of the trivalent rare-earth cations from their alkali and alkaline-earth peers is in the presence of localized 4f-electrons and strong spin-orbit coupling. Placing trivalent rare-earth cations inside the fullerene molecules or in between the blocks of itinerant magnetic intermetallics gave rise to plethora of fascinating properties and materials. A long-time missing but hardly desired piece is the semiconducting or metallic compound where rare-earth cations are situated inside the oversized polyhedral cages of three-dimensional framework. In this work we present a synthesis of such compounds, rare-earth containing clathrates Ba8-xRxCu16P30. The unambiguous proofs of their composition and crystal structure were achieved by a combination of synchrotron powder diffraction, time-of-flight neutron powder diffraction, scanning-transmission electron microscopy, and electron energy-loss spectroscopy. Our quantum-mechanical calculations and experimental characterizations show that the incorporation of the rare-earth cations significantly enhances the hole mobility and concentration which results in the drastic increase in the thermoelectric performance.

  7. Liquid structure and melting of trivalent metal chlorides

    International Nuclear Information System (INIS)

    Tosi, M.P.; Pastore, G.; Saboungi, M.L.; Price, D.L.

    1991-03-01

    Many divalent and trivalent metal ions in stoichiometric liquid mixtures of their halides with alkali halides are fourfold or sixfold coordinated by halogens into relatively long-lived ''complexes''. The stability of these local coordination states and the connectivity that arises between them in the approach to the pure polyvalent metal halide melt determines the character of its short-range and possible intermediate-range order. The available evidence on local coordination in some 140 mixtures has been successfully classified by a structure sorting method based on Pettifor's chemical scale of the elements. Within the general phenomenological frame provided by structure sorting, main attention is given in this work to the liquid structure and melting mechanisms of trivalent metal chlorides. The liquid structure of YCl 3 is first discussed on the basis of neutron diffraction measurements and of calculations within a simple ionic model, and the melting mechanisms of YCl 3 and AlCl 3 , which are structurally isomorphous in the crystalline state, are contrasted. By appeal to macroscopic melting parameters and transport coefficients and to liquid structure data on SbCl 3 , it is proposed that the melting mechanisms of these salts may be classified into three main types in correlation with the character of the chemical bond. (author). 31 refs, 1 fig., 3 tabs

  8. Influenza (Flu)

    Science.gov (United States)

    ... develop influenza. Weakened immune system. Cancer treatments, anti-rejection drugs, corticosteroids and HIV/AIDS can weaken your ... for Disease Control and Prevention recommends annual flu vaccination for everyone over the age of 6 months. ...

  9. Intradermal and virosomal influenza vaccines for preventing influenza hospitalization in the elderly during the 2011-2012 influenza season: a comparative effectiveness study using the Valencia health care information system.

    Science.gov (United States)

    Puig-Barberà, J; Natividad-Sancho, A; Calabuig-Pérez, J; Lluch-Rodrigo, J A; Pastor-Villalba, E; Martínez-Úbeda, S; Díez-Domingo, J

    2014-09-22

    The use of intradermal vaccination or virosomal vaccines could increase protection against influenza among the vulnerable population of older adults. Studies assessing the comparative effectiveness of these two influenza vaccine types in this age group are lacking. We conducted a retrospective cohort study to estimate the comparative effectiveness of intradermal seasonal trivalent-influenza vaccine (TIV) delivered by a microneedle injection system and a virosomal-TIV intramuscularly delivered for prevention of influenza hospitalization in non-institutionalized adults aged ≥65 years. We obtained administrative data on immunization status and influenza hospitalization for the 2011-2012 influenza season, and used Cox regression models to assess comparative effectiveness. We estimated crude and adjusted (age, sex, comorbidity, pharmaceutical claims, recent pneumococcal vaccination and number of hospitalizations for all causes other than influenza between the previous and current influenza seasons) hazard ratios (HR). Overall, 164,021 vaccinated subjects were evaluated. There were 127 hospitalizations for influenza among 62,058 subjects, contributing 914,740 person-weeks at risk in the virosomal-TIV group, and 133 hospitalizations for influenza among 101,963 subjects, contributing 1,504,570 person-weeks at risk in the intradermal-TIV group. The crude HR of intradermal-TIV relative to virosomal-TIV was 0.64 (95% confidence interval (CI): 0.50-0.81), and the adjusted Cox estimated HR was 0.67 (95% CI: 0.52-0.85). During the 2011-2012 influenza season the risk of hospitalization for influenza was reduced by 33% in non-institutionalized elderly adults who were vaccinated with intradermal-TIV compared with virosomal-TIV. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  10. Response to 2009 pandemic influenza A (H1N1 vaccine in HIV-infected patients and the influence of prior seasonal influenza vaccination.

    Directory of Open Access Journals (Sweden)

    Darius Soonawala

    2011-01-01

    Full Text Available The immunogenicity of 2009 pandemic influenza A(H1N1 (pH1N1 vaccines and the effect of previous influenza vaccination is a matter of current interest and debate. We measured the immune response to pH1N1 vaccine in HIV-infected patients and in healthy controls. In addition we tested whether recent vaccination with seasonal trivalent inactivated vaccine (TIV induced cross-reactive antibodies to pH1N1. (clinicaltrials.gov Identifier:NCT01066169.In this single-center prospective cohort study MF59-adjuvanted pH1N1 vaccine (Focetria®, Novartis was administered twice to 58 adult HIV-infected patients and 44 healthy controls in November 2009 (day 0 and day 21. Antibody responses were measured at baseline, day 21 and day 56 with hemagglutination-inhibition (HI assay. The seroprotection rate (defined as HI titers ≥ 1 : 40 for HIV-infected patients was 88% after the first and 91% after the second vaccination. These rates were comparable to those in healthy controls. Post-vaccination GMT, a sensitive marker of the immune competence of a group, was lower in HIV-infected patients. We found a high seroprotection rate at baseline (31%. Seroprotective titers at baseline were much more common in those who had received 2009-2010 seasonal TIV three weeks prior to the first dose of pH1N1 vaccine. Using stored serum samples of 51 HIV-infected participants we measured the pH1N1 specific response to 2009-2010 seasonal TIV. The seroprotection rate to pH1N1 increased from 22% to 49% after vaccination with 2009-2010 seasonal TIV. Seasonal TIV induced higher levels of antibodies to pH1N1 in older than in younger subjects.In HIV-infected patients on combination antiretroviral therapy, with a median CD4+ T-lymphocyte count above 500 cells/mm(3, one dose of MF59-adjuvanted pH1N1 vaccine induced a high seroprotection rate comparable to that in healthy controls. A second dose had a modest additional effect. Furthermore, seasonal TIV induced cross-reactive antibodies to pH1N1

  11. The effectiveness of influenza vaccination in preventing hospitalizations in children in Hong Kong, 2009-2013.

    Science.gov (United States)

    Cowling, Benjamin J; Chan, Kwok-Hung; Feng, Shuo; Chan, Eunice L Y; Lo, Janice Y C; Peiris, J S Malik; Chiu, Susan S

    2014-09-15

    Influenza vaccination is widely recommended every year to protect individuals against influenza virus infection and illness. There are few published estimates of influenza vaccine effectiveness against hospitalization in children or from subtropical regions. We conducted a test-negative year-round study between October 2009 and September 2013, recruiting children 6 months to 17 years of age admitted to two hospitals in Hong Kong with a febrile acute respiratory infection. Cases were tested for influenza A and B and conditional logistic regression was used to estimate vaccine effectiveness comparing influenza vaccination history of the trivalent influenza vaccine (TIV) among patients testing positive versus negative for influenza, adjusting for age and sex and matching by calendar week of recruitment. Overall vaccine effectiveness against hospitalization with laboratory-confirmed influenza A and B was estimated to be 61.7% (95% CI: 43.0%, 74.2%). The estimated vaccine effectiveness against A(H3N2) was 36.6% (95% CI: -25.5%, 67.9%) compared to 71.5% (95% CI: 39.4%, 86.6%) for A(H1N1)pdm09 and 68.8% (95% CI: 41.6%, 83.3%) for B. Vaccine effectiveness against hospitalization in children varied from year to year, but was moderate to high overall even in an area with influenza activity throughout the year. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Trends of influenza B during the 2010-2016 seasons in 2 regions of north and south Italy: The impact of the vaccine mismatch on influenza immunisation strategy.

    Science.gov (United States)

    Orsi, Andrea; Colomba, Giuseppina Maria Elena; Pojero, Fanny; Calamusa, Giuseppe; Alicino, Cristiano; Trucchi, Cecilia; Canepa, Paola; Ansaldi, Filippo; Vitale, Francesco; Tramuto, Fabio

    2018-03-04

    Influenza A and B viruses are responsible for respiratory infections, representing globally seasonal threats to human health. The 2 viral types often co-circulate and influenza B plays an important role in the spread of infection. A 6-year retrospective surveillance study was conducted between 2010 and 2016 in 2 large administrative regions of Italy, located in the north (Liguria) and in the south (Sicily) of the country, to describe the burden and epidemiology of both B/Victoria and B/Yamagata lineages in different healthcare settings. Influenza B viruses were detected in 5 of 6 seasonal outbreaks, exceeding influenza A during the season 2012-2013. Most of influenza B infections were found in children aged ≤ 14 y and significant differences were observed in the age-groups infected by the different lineages. B/Victoria strains prevailed in younger population than B/Yamagata, but also were more frequently found in the community setting. Conversely, B/Yamagata viruses were prevalent among hospitalized cases suggesting their potential role in the development of more severe disease. The relative proportions of viral lineages varied from year to year, resulting in different lineage-level mismatch for the B component of trivalent influenza vaccine. Our findings confirmed the need for continuous virological surveillance of seasonal epidemics and bring attention to the adoption of universal influenza immunization program in the childhood. The use of tetravalent vaccine formulations may be useful to improve the prevention and control of the influenza burden in general population.

  13. Association between the 2008-09 seasonal influenza vaccine and pandemic H1N1 illness during Spring-Summer 2009: four observational studies from Canada.

    Directory of Open Access Journals (Sweden)

    Danuta M Skowronski

    2010-04-01

    Full Text Available In late spring 2009, concern was raised in Canada that prior vaccination with the 2008-09 trivalent inactivated influenza vaccine (TIV was associated with increased risk of pandemic influenza A (H1N1 (pH1N1 illness. Several epidemiologic investigations were conducted through the summer to assess this putative association.(1 test-negative case-control design based on Canada's sentinel vaccine effectiveness monitoring system in British Columbia, Alberta, Ontario, and Quebec; (2 conventional case-control design using population controls in Quebec; (3 test-negative case-control design in Ontario; and (4 prospective household transmission (cohort study in Quebec. Logistic regression was used to estimate odds ratios for TIV effect on community- or hospital-based laboratory-confirmed seasonal or pH1N1 influenza cases compared to controls with restriction, stratification, and adjustment for covariates including combinations of age, sex, comorbidity, timeliness of medical visit, prior physician visits, and/or health care worker (HCW status. For the prospective study risk ratios were computed. Based on the sentinel study of 672 cases and 857 controls, 2008-09 TIV was associated with statistically significant protection against seasonal influenza (odds ratio 0.44, 95% CI 0.33-0.59. In contrast, estimates from the sentinel and three other observational studies, involving a total of 1,226 laboratory-confirmed pH1N1 cases and 1,505 controls, indicated that prior receipt of 2008-09 TIV was associated with increased risk of medically attended pH1N1 illness during the spring-summer 2009, with estimated risk or odds ratios ranging from 1.4 to 2.5. Risk of pH1N1 hospitalization was not further increased among vaccinated people when comparing hospitalized to community cases.Prior receipt of 2008-09 TIV was associated with increased risk of medically attended pH1N1 illness during the spring-summer 2009 in Canada. The occurrence of bias (selection, information or

  14. Universal influenza vaccines: Shifting to better vaccines.

    Science.gov (United States)

    Berlanda Scorza, Francesco; Tsvetnitsky, Vadim; Donnelly, John J

    2016-06-03

    Influenza virus causes acute upper and lower respiratory infections and is the most likely, among known pathogens, to cause a large epidemic in humans. Influenza virus mutates rapidly, enabling it to evade natural and vaccine-induced immunity. Furthermore, influenza viruses can cross from animals to humans, generating novel, potentially pandemic strains. Currently available influenza vaccines induce a strain specific response and may be ineffective against new influenza viruses. The difficulty in predicting circulating strains has frequently resulted in mismatch between the annual vaccine and circulating viruses. Low-resource countries remain mostly unprotected against seasonal influenza and are particularly vulnerable to future pandemics, in part, because investments in vaccine manufacturing and stockpiling are concentrated in high-resource countries. Antibodies that target conserved sites in the hemagglutinin stalk have been isolated from humans and shown to confer protection in animal models, suggesting that broadly protective immunity may be possible. Several innovative influenza vaccine candidates are currently in preclinical or early clinical development. New technologies include adjuvants, synthetic peptides, virus-like particles (VLPs), DNA vectors, messenger RNA, viral vectors, and attenuated or inactivated influenza viruses. Other approaches target the conserved exposed epitope of the surface exposed membrane matrix protein M2e. Well-conserved influenza proteins, such as nucleoprotein and matrix protein, are mainly targeted for developing strong cross-protective T cell responses. With multiple vaccine candidates moving along the testing and development pipeline, the field is steadily moving toward a product that is more potent, durable, and broadly protective than previously licensed vaccines. Copyright © 2016 World Health Organization. Published by Elsevier Ltd.. All rights reserved.

  15. Immunogenicity and safety of an inactivated hepatitis A vaccine when coadministered with Diphtheria-tetanus-acellular pertussis and haemophilus influenzae type B vaccines in children 15 months of age.

    Science.gov (United States)

    Trofa, Andrew F; Klein, Nicola P; Paul, Ian M; Michaels, Marian G; Goessler, Mary; Chandrasekaran, Vijayalakshmi; Blatter, Mark

    2011-09-01

    This study (NCT00197236) evaluated the safety and immunogenicity of a hepatitis A virus (HAV) vaccine when coadministered with diphtheria-tetanus-acellular pertussis (DTaP) and Haemophilus influenzae type b (Hib) vaccines in children 15 months of age. This was an open-labeled, multicenter study with healthy subjects enrolled and randomized (1:1:1) into 3 treatment groups. A total of 394 subjects received the first study vaccinations at 15 months of age. Group HAV (N = 135) received 2 doses of HAV vaccine 6 to 9 months apart. Group HAV+DTaP+Hib (N = 127) received HAV vaccine coadministered with DTaP and Hib vaccines and the second dose of HAV vaccine, 6 to 9 months later. Group DTaP+Hib→HAV (N = 132) received the DTaP and Hib vaccines at 15 months of age, followed by HAV vaccine 30 days later and the second dose of HAV vaccine 7 to 10 months after the DTaP+Hib vaccines. Immune responses were evaluated before the first study vaccination and 30 days after each vaccine dose. Solicited, unsolicited, and serious adverse events were collected. After 2 doses of the HAV vaccine, all subjects in the 3 groups were seropositive. The geometric mean concentration of anti-HAV antibodies ranged between 1625.1 and 1904.4 mIU/mL. Coadministration of the 3 vaccines did not impact immunogenicity of the HAV, DTaP, or Hib vaccines. Vaccines were well tolerated in all groups. A 2-dose schedule of HAV vaccine was well tolerated and immunogenic when administered to children starting at 15 months of age. Immune responses to the DTaP or Hib vaccines were similar whether they were administered alone or were coadministered with the HAV vaccine.

  16. Bistable luminescence of trivalent rare-earth ions in crystals

    International Nuclear Information System (INIS)

    Sole, Jose Garcia; Ramirez O, Maria de la; Rodenas, Airan; Jaque, Daniel; Bausa, Luisa; Bettinelli, Marco; Speghini, Adolfo; Cavalli, Enrico; Ivleva, Lioudmila

    2006-01-01

    In this work, we have examined three new bistable systems based on the luminescence of three different crystals activated with trivalent rare earth ions. We have focussed our attention on Yb 3+ ions activators, for which the most relevant results are obtained. The first crystal, Sr 0.6 Ba 0.4 Nb 2 O 6 , is a ferroelectric material with a relatively low phase transition temperature (∼370 K), which provides bistability in the luminescence of Yb 3+ ions due to the thermal hysteresis associated with phase transition. The second crystal, LiNbO 3 , provides an intrinsic bistability in the luminescence of Yb 3+ ions, which is driven by changes in the excitation intensity. In the third crystal, NdPO 4 , a new mechanism of excitation intensity driven bistability is obtained when activated with Yb 3+ ions, due to a interplay between the Nd 3+ ↔Yb 3+ energy transfer and back transfer processes

  17. Atomistic Simulation of Intrinsic Defects and Trivalent and Tetravalent Ion Doping in Hydroxyapatite

    Directory of Open Access Journals (Sweden)

    Ricardo D. S. Santos

    2014-01-01

    Full Text Available Atomistic simulation techniques have been employed in order to investigate key issues related to intrinsic defects and a variety of dopants from trivalent and tetravalent ions. The most favorable intrinsic defect is determined to be a scheme involving calcium and hydroxyl vacancies. It is found that trivalent ions have an energetic preference for the Ca site, while tetravalent ions can enter P sites. Charge compensation is predicted to occur basically via three schemes. In general, the charge compensation via the formation of calcium vacancies is more favorable. Trivalent dopant ions are more stable than tetravalent dopants.

  18. An open-label randomized clinical trial of prophylactic paracetamol coadministered with 7-valent pneumococcal conjugate vaccine and hexavalent diphtheria toxoid, tetanus toxoid, 3-component acellular pertussis, hepatitis B, inactivated poliovirus, and Haemophilus influenzae type b vaccine.

    Science.gov (United States)

    Rose, Markus A; Juergens, Christine; Schmoele-Thoma, Beate; Gruber, William C; Baker, Sherryl; Zielen, Stefan

    2013-06-21

    In two clinical trials, low-grade fever was observed more frequently after coadministration than after separate administration of two recommended routine pediatric vaccines. Since fever is an important issue with vaccine tolerability, we performed this open-label study on the efficacy and safety of prophylactic use of paracetamol (acetaminophen, Benuron®) in children administered routine 7-valent pneumococcal conjugate vaccine (PCV-7) coadministered with hexavalent vaccine (diphtheria-tetanus-acellular pertussis-hepatitis B, poliovirus, Haemophilus influenzae type b vaccine [DTPa-HBV-IPV/Hib]) in Germany. Healthy infants (N = 301) who received a 3-dose infant series of PCV-7 and DTPa-HBV-IPV/Hib plus a toddler dose were randomly assigned 1:1 to prophylactic paracetamol (125 mg or 250 mg suppositories, based on body weight) at vaccination, and at 6-8 hour intervals thereafter, or a control group that received no paracetamol. Rectal temperature and local and other systemic reactions were measured for 4 days post vaccination; adverse events were collected throughout the study. In the intent-to-treat population, paracetamol reduced the incidence of fever ≥38°C, but this reduction was only significant for the infant series, with computed efficacy of 43.0% (95% confidence interval [CI]: 17.4, 61.2), and not significant after the toddler dose (efficacy 15.9%; 95% CI: -19.9, 41.3); results were similar in the per protocol (PP) population. Fever >39°C was rare during the infant series, such that there were too few cases for assessment. After the toddler dose, paracetamol effectively reduced fever >39°C, reaching statistical significance in the PP population only (efficacy 79%; 95% CI: 3.9, 97.7). Paracetamol also reduced reactogenicity, but there were few significant differences between groups after any dose. No vaccine-related serious adverse events were reported. Paracetamol effectively prevented fever and other reactions, mainly during the infant series

  19. Avian Influenza.

    Science.gov (United States)

    Zeitlin, Gary Adam; Maslow, Melanie Jane

    2005-05-01

    The current epidemic of H5N1 highly pathogenic avian influenza in Southeast Asia raises serious concerns that genetic reassortment will result in the next influenza pandemic. There have been 164 confirmed cases of human infection with avian influenza since 1996. In 2004, there were 45 cases of human H5N1 in Vietnam and Thailand, with a mortality rate more than 70%. In addition to the potential public health hazard, the current zoonotic epidemic has caused severe economic losses. Efforts must be concentrated on early detection of bird outbreaks with aggressive culling, quarantining, and disinfection. To prepare for and prevent an increase in human cases, it is essential to improve detection methods and stockpile effective antivirals. Novel therapeutic modalities, including short-interfering RNAs and new vaccine strategies that use plasmid-based genetic systems, offer promise should a pandemic occur.

  20. Immune responses after live attenuated influenza vaccination

    Science.gov (United States)

    Mohn, Kristin G.-I.; Smith, Ingrid; Sjursen, Haakon; Cox, Rebecca Jane

    2018-01-01

    ABSTRACT Since 2003 (US) and 2012 (Europe) the live attenuated influenza vaccine (LAIV) has been used as an alternative to the traditional inactivated influenza vaccines (IIV). The immune responses elicted by LAIV mimic natural infection and have been found to provide broader clinical protection in children compared to the IIVs. However, our knowledge of the detailed immunological mechanisims induced by LAIV remain to be fully elucidated, and despite 14 years on the global market, there exists no correlate of protection. Recently, matters are further complicated by differing efficacy data from the US and Europe which are not understood. Better understanding of the immune responses after LAIV may aid in achieving the ultimate goal of a future “universal influenza vaccine”. In this review we aim to cover the current understanding of the immune responses induced after LAIV. PMID:28933664

  1. Influenza vaccines: Evaluation of the safety profile

    Science.gov (United States)

    Trombetta, Claudia Maria; Gianchecchi, Elena; Montomoli, Emanuele

    2018-01-01

    ABSTRACT The safety of vaccines is a critical factor in maintaining public trust in national vaccination programs. Vaccines are recommended for children, adults and elderly subjects and have to meet higher safety standards, since they are administered to healthy subjects, mainly healthy children. Although vaccines are strictly monitored before authorization, the possibility of adverse events and/or rare adverse events cannot be totally eliminated. Two main types of influenza vaccines are currently available: parenteral inactivated influenza vaccines and intranasal live attenuated vaccines. Both display a good safety profile in adults and children. However, they can cause adverse events and/or rare adverse events, some of which are more prevalent in children, while others with a higher prevalence in adults. The aim of this review is to provide an overview of influenza vaccine safety according to target groups, vaccine types and production methods. PMID:29297746

  2. MF59-adjuvanted and virosomal influenza vaccines for preventing influenza hospitalization in older people: comparative effectiveness using the Valencia health care information system.

    Science.gov (United States)

    Puig-Barberà, J; Natividad-Sancho, A; Calabuig-Pérez, J; Lluch-Rodrigo, J A; Pastor-Villalba, E; Martínez-Úbeda, S; Pérez-Vilar, S; Díez-Domingo, J

    2013-08-20

    Adjuvanted influenza vaccines offer greater and broader immunogenicity to older adults than conventional vaccines. Studies assessing the comparative effectiveness of adjuvanted influenza vaccines in this age group are lacking. We conducted a retrospective cohort study to estimate the comparative effectiveness of MF59-adjuvanted trivalent influenza vaccine (TIV) and virosomal-TIV for prevention of influenza hospitalization in adults aged ≥65 years. We obtained administrative data on immunization status and influenza hospitalization for the 2010-2011 influenza season. We used Cox regression models to assess comparative effectiveness; crude and adjusted by age, sex, comorbidity, deprivation, type of insurance, and travel time to hospital. We accounted for data clustering at the hospital level by using a multilevel random effects model. Overall, 373,798 vaccinated subjects were evaluated. There were 40 hospitalizations for influenza among 176,618 subjects, contributing 4,288,109 person-weeks at risk in the virosomal-TIV group, and 37 hospitalizations for influenza among 197,180 subjects, contributing 4,786,360 person-weeks at risk in the MF59-TIV group. The crude hazard ratio (HR) was 0.83 (0.53-1.30), and the adjusted Cox estimated HR of MF59-TIV relative to virosomal-TIV was 0.86 (0.55-1.35). After accounting for data clustering, the HR of influenza hospitalization associated with MF59-TIV relative to virosomal-TIV was 0.94 (0.37-2.38). During the 2010-2011 influenza season, we found no differences in the risk of influenza hospitalization in subjects aged ≥65 years vaccinated with MF59-TIV compared with those vaccinated with virosomal-TIV. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Avian influenza

    DEFF Research Database (Denmark)

    EFSA Panel on Animal Health and Welfare; More, Simon; Bicout, Dominique

    2017-01-01

    Previous introductions of highly pathogenic avian influenza virus (HPAIV) to the EU were most likely via migratory wild birds. A mathematical model has been developed which indicated that virus amplification and spread may take place when wild bird populations of sufficient size within EU become...... infected. Low pathogenic avian influenza virus (LPAIV) may reach similar maximum prevalence levels in wild bird populations to HPAIV but the risk of LPAIV infection of a poultry holding was estimated to be lower than that of HPAIV. Only few non-wild bird pathways were identified having a non...

  4. Prophage induction and inactivation by uv light

    International Nuclear Information System (INIS)

    Barnhart, B.J.; Cox, S.H.; Jett, J.H.

    1976-01-01

    Analysis of the induction curves for uv light-irradiated Haemophilus influenzae lysogens and the distribution of pyrimidine dimers in a repair-deficient lysogen suggests that one dimer per prophage-size segment of the host bacterial chromosome is necessary as a preinduction event. The close correlations obtained prompted a renewed consideration of the possibility that direct prophage induction occurs when one dimer is stabilized within the prophage genome. The host excision-repair system apparently functions to reduce the probability of stabilizing within the prophage those dimers that are necessary for induction and inactivation. The presence of the inducible defective prophage in strain Rd depresses the inducibility of prophage HP1c1

  5. Avian Influenza (Bird Flu)

    Science.gov (United States)

    ... in People Spread of Bird Flu Viruses Between Animals and People Examples of Human Infections with Avian Influenza A ... Subtypes Transmission of Avian Influenza A Viruses Between Animals and People Related Links Research Glossary of Influenza (Flu) Terms ...

  6. Molecular epidemiology of influenza B virus among hospitalized pediatric patients in Northern Italy during the 2015-16 season.

    Directory of Open Access Journals (Sweden)

    Antonio Piralla

    Full Text Available The influenza B viruses belong to two lineages distinguished by their genetic and antigenic characteristics, which are referred to as the Yamagata and Victoria lineages, designated after their original isolates, B/Yamagata/16/88 and B/Victoria/2/87. The primary aim of this study was to evaluate the molecular characteristics of influenza B viruses circulating in a region of Northern Italy, Lombardia, during the influenza season of 2015-2016.Influenza B virus was detected using a respiratory virus panel of assays and an influenza B-specific real-time polymerase chain reaction. The complete influenza B hemagglutinin (HA gene was amplified and sequenced directly from clinical specimens. Phylogenetic analysis was performed using nucleotide sequences.A total of 71 hospitalized pediatric patients were influenza B positive. Phylogenetic analysis showed that the great majority of influenza B strains (66/71, 93.0% belonged to the Victoria-lineage and were antigenically like vaccine strain (B/Brisbane/60/2008 included only in the quadrivalent vaccine. In the detected influenza B strains, a series of amino acid changes were observed in the antigenic regions: I117V, V124A, N129D, V146I, N197D, T199A, and A202T. However, only 2 amino acid changes were observed in the HA regions involved in receptor binding or in antibody recognition.All the influenza B strains identified in this study belonged to the influenza B Victoria lineage not included in the trivalent vaccine commonly used by the general population during the 2015-2016 influenza season in Italy. This indicates that protection against influenza B infection in the vaccinated population was in general very poor during the 2015-2016 influenza season.

  7. Trivalent europium speciation in a room-temperature ionic liquid

    International Nuclear Information System (INIS)

    Mekki, S.

    2006-10-01

    Since the nuclear industry is playing an important role in the power production field, a relevant number of problems have been revealed. Indeed, high-level radioactive long-lived nuclear wastes present a real difficulty for nuclear wastes management. Minor actinides, which compose most of these wastes, will be radioactive for several thousands of years. For eventual disposal deep underground, their reprocessing needs to be optimized. The extraction processes used industrially to separate actinides and lanthanides from other metal species characterizing the spent nuclear fuel produce, nevertheless, enormous quantities of contaminated liquid wastes directly issued from the liquid/liquid extraction step. During the last decade, some room-temperature ionic liquid have been studied and integrated into industrial processes. The interest on this class of solvent came out from their 'green' properties (non volatile, non flammable, recyclable, etc...), but also from the variability of their physico-chemical properties (stability, hydrophobicity, viscosity) as a function of the RTIL chemical composition. Indeed, it has been shown that classical chemical industrial processes could be transferred into those media, even more improved, while a certain number of difficulties arising from using traditional solvent can be avoided. In this respect, it could be promising to investigate the ability to use room-temperature ionic liquid into the spent nuclear fuel reprocessing field. The aim of this thesis is to test the ability of the specific ionic liquid bumimTf 2 N to allow trivalent europium extraction. The choice of this metal is based on the chemical analogy with trivalent minor actinides Curium and Americium which are contributing the greatest part of the long-lived high-level radioactive wastes. Handling these elements needs to be very cautious for the safety and radioprotection aspect. Moreover, europium is a very sensitive luminescent probe to its environment even at the

  8. Synthesis, characterization and luminescence spectroscopy of oxide nanopowders activated with trivalent lanthanide ions: The garnet family

    Science.gov (United States)

    Speghini, Adolfo; Piccinelli, Fabio; Bettinelli, Marco

    2011-01-01

    In this review, we deal with the preparation, structural investigation and especially optical spectroscopy of the garnet family of oxide materials activated with trivalent lanthanide ions, in the nanocrystalline form. In particular, attention is devoted here to the important garnet hosts; their synthesis, structure and luminescence spectroscopy are presented and discussed, with particular emphasis given to the possibility of obtaining efficient luminescence from trivalent lanthanide ions at the nanoscale, and to the potential and envisaged technological applications of this class of materials.

  9. Spectroscopic properties of trivalent Europium in various composites with an eulytin structure. Internship report

    International Nuclear Information System (INIS)

    Raynal, Francoise

    1975-01-01

    Eulytin is a bismuth orthosilicate and eulytin compounds revealed to be interesting matrix materials which can be used as medium gain laser materials. This research report is thus a contribution for a better knowledge of this material. Different eulytin compounds doped with lanthanide ions have been used to study the cationic polyhedron (by using structural probes such as the trivalent Europium in spectroscopy, or the trivalent gadolinium in electronic paramagnetic resonance) and the anionic polyhedron

  10. A DNA Vaccine-Encoded Nucleoprotein of Influenza Virus Fails To Induce Cellular Immune Responses in a Diabetic Mouse Model▿

    OpenAIRE

    Jamali, Abbas; Sabahi, Farzaneh; Bamdad, Taravat; Hashemi, Hamidreza; Mahboudi, Fereidoun; Kheiri, Masume Tavasoti

    2010-01-01

    International audience; Influenza virus infections cause yearly epidemics and are a major cause of lower respiratory tract illnesses in humans worldwide. Influenza virus has long been recognized to be associated with higher morbidity and mortality in diabetic patients. Vaccination is an effective tool to prevent influenza virus infection in this group of patients. Vaccines employing recombinant-DNA technologies are an alternative to inactivated virus and live attenuated virus vaccines. Intern...

  11. School-Located Influenza Vaccination Decreases Laboratory-Confirmed Influenza and Improves School Attendance

    Science.gov (United States)

    Pannaraj, Pia S.; Wang, Hai-Lin; Rivas, Hector; Wiryawan, Hilda; Smit, Michael; Green, Nicole; Aldrovandi, Grace M.; El Amin, Alvin Nelson; Mascola, Laurene

    2014-01-01

    Background. School-located influenza vaccination (SLV) programs can efficiently immunize large numbers of school-aged children. We evaluated the impact of SLV on laboratory-confirmed influenza and absenteeism. Methods. Active surveillance for influenza-like illness (ILI) was conducted on 4455 children in 4 SLV intervention and 4 control elementary schools (grades K–6) matched for sociodemographic characteristics during the 2010–2011 influenza season in Los Angeles County, California. Combined nose/throat swabs were collected from febrile children with ILI at presentation to the school nurse or during absenteeism. Results. In SLV schools, 26.9%–46.6% of enrolled students received at least 1 dose of either inactivated or live attenuated influenza vaccine compared with 0.8%–4.3% in control schools. Polymerase chain reaction for respiratory viruses (PCR) was performed on 1021 specimens obtained from 898 children. Specimens were positive for influenza in 217 (21.3%), including 2009 H1N1 (30.9%), H3 (9.2%), and B (59.9%). Children attending SLV schools, regardless of vaccination status, were 30.8% (95% confidence interval, 10.1%–46.8%) less likely to acquire influenza compared with children at control schools. Unvaccinated children were indirectly protected in the school with nearly 50% vaccination coverage compared with control schools (influenza rate, 27.1 vs 60.0 per 1000 children; P = .023). Unvaccinated children missed more school days than vaccinated children (4.3 vs 2.8 days per 100 school days; P school population resulted in decreased influenza rates and improved school attendance. Herd immunity for unvaccinated children may occur in schools with vaccination coverage approaching 50%. PMID:24829215

  12. Thermal Inactivation of Viruses

    Science.gov (United States)

    1977-10-01

    production. Proc. Soc. Exptl. Biol. Med. 116:174-177. Mayer, V. 1965. Study of the virulence of tick-borne encephalitis virus. IV. Thermosensitivity...inactivation of rabies and other rhabrtoviruses: stabilization of the chelating agent Ethylenediaminetetraacetic acid at physiological temperatures. Infec

  13. New insights into formation of trivalent actinides complexes with DTPA.

    Science.gov (United States)

    Leguay, Sébastien; Vercouter, Thomas; Topin, Sylvain; Aupiais, Jean; Guillaumont, Dominique; Miguirditchian, Manuel; Moisy, Philippe; Le Naour, Claire

    2012-12-03

    Complexation of trivalent actinides with DTPA (diethylenetriamine pentaacetic acid) was studied as a function of pcH and temperature in (Na,H)Cl medium of 0.1 M ionic strength. Formation constants of both complexes AnHDTPA(-) and AnDTPA(2-) (where An stands for Am, Cm, and Cf) were determined by TRLFS, CE-ICP-MS, spectrophotometry, and solvent extraction. The values of formation constants obtained from the different techniques are coherent and consistent with reinterpreted literature data, showing a higher stability of Cf complexes than Am and Cm complexes. The effect of temperature indicates that formation constants of protonated and nonprotonated complexes are exothermic with a high positive entropic contribution. DFT calculations were also performed on the An/DTPA system. Geometry optimizations were conducted on AnDTPA(2-) and AnHDTPA(-) considering all possible protonation sites. For both complexes, one and two water molecules in the first coordination sphere of curium were also considered. DFT calculations indicate that the lowest energy structures correspond to protonation on oxygen that is not involved in An-DTPA bonds and that the structures with two water molecules are not stable.

  14. Butyroyl-arginine as a potent virus inactivation agent.

    Science.gov (United States)

    Katsuyama, Yukiko; Yamasaki, Hisashi; Tsujimoto, Kazuko; Koyama, A Hajime; Ejima, Daisuke; Arakawa, Tsutomu

    2008-09-01

    Virus inactivation is a critical step in the manufacturing of recombinant therapeutic proteins, in particular antibodies, using mammalian expression systems. We have shown in the previous paper that arginine is effective in inactivation of herpes simplex virus type 1 (HSV-1) and influenza virus at low temperature under mildly acidic pH, i.e., above pH 4.0; above this pH, conformational changes of most antibodies are negligible. We have here extended virus inactivation study of arginine to other enveloped viruses, such as Sendai virus and Newcastle Disease Virus (NDV), and observed that arginine was ineffective against both viruses under the similar conditions, i.e., on ice and above pH 4.0. However, an arginine derivative, butyroyl-arginine, showed a strong virucidal potency against Sendai virus, leading to a 4log reduction in virus yield at pH 4.0, but not against NDV. In addition, although arginine and butyroyl-arginine were equally effective against influenza virus having a cleaved form of hemagglutinin spike proteins, only butyroyl-arginine was significantly effective against the same virus, but having an uncleaved hemagglutinin spike proteins. Furthermore, butyroyl-arginine was more effective than arginine against HSV-1 at pH 4.5; i.e., it has a broader pH spectrum than does arginine.

  15. Influenza vaccine effectiveness for hospital and community patients using control groups with and without non-influenza respiratory viruses detected, Auckland, New Zealand 2014.

    Science.gov (United States)

    Pierse, Nevil; Kelly, Heath; Thompson, Mark G; Bissielo, Ange; Radke, Sarah; Huang, Q Sue; Baker, Michael G; Turner, Nikki

    2016-01-20

    We aimed to estimate the protection afforded by inactivated influenza vaccine, in both community and hospital settings, in a well characterised urban population in Auckland during 2014. We used two different comparison groups, all patients who tested negative for influenza and only those patients who tested negative for influenza and had a non-influenza respiratory virus detected, to calculate the vaccine effectiveness in a test negative study design. Estimates were made separately for general practice outpatient consultations and hospitalised patients, stratified by age group and by influenza type and subtype. Vaccine status was confirmed by electronic record for general practice patients and all respiratory viruses were detected by real time polymerase chain reaction. 1039 hospitalised and 1154 general practice outpatient consultations met all the study inclusion criteria and had a respiratory sample tested for influenza and other respiratory viruses. Compared to general practice patients, hospitalised patients were more likely to be very young or very old, to be Māori or Pacific Islander, to have a low income and to suffer from chronic disease. Vaccine effectiveness (VE) adjusted for age and other participant characteristics using all influenza negative controls was 42% (95% CI: 16 to 60%) for hospitalised and 56% (95% CI: 35 to 70%) for general practice patients. The vaccine appeared to be most effective against the influenza A(H1N1)pdm09 strain with an adjusted VE of 62% (95% CI:38 to 77%) for hospitalised and 59% (95% CI:36 to 74%) for general practice patients, using influenza virus negative controls. Similar results found when patients testing positive for a non-influenza respiratory virus were used as the control group. This study contributes to validation of the test negative design and confirms that inactivated influenza vaccines continue to provide modest but significant protection against laboratory-confirmed influenza. Copyright © 2015 Elsevier Ltd

  16. Long-term stability of influenza vaccine in a dissolving microneedle patch.

    Science.gov (United States)

    Mistilis, Matthew J; Joyce, Jessica C; Esser, E Stein; Skountzou, Ioanna; Compans, Richard W; Bommarius, Andreas S; Prausnitz, Mark R

    2017-04-01

    This study tested the hypothesis that optimized microneedle patch formulations can stabilize trivalent subunit influenza vaccine during long-term storage outside the cold chain and when exposed to potential stresses found during manufacturing and storage. Formulations containing combinations of trehalose/sucrose, sucrose/arginine, and arginine/heptagluconate were successful at retaining most or all vaccine activity during storage at 25 °C for up to 24 months as determined by ELISA assay. The best formulation of microneedle patches contained arginine/heptagluconate, which showed no significant loss of vaccine activity during the study. To validate these in vitro findings, mice were immunized using trivalent influenza vaccine stored in microneedle patches for more than 1 year at 25 °C, which elicited antibody titers greater than or equal to fresh liquid vaccine delivered by intradermal injection, indicating the retention of immunogenicity during storage. Finally, influenza vaccine in microneedle patches lost no significant activity during exposure to 60 °C for 4 months, multiple freeze-thaw cycles, or electron beam irradiation. We conclude that optimally formulated microneedle patches can retain influenza vaccine activity during extended storage outside the cold chain and during other environmental stresses, which suggests the possibility of microneedle patch storage on pharmacy shelves without refrigeration.

  17. SAFETY OF CELL-DERIVED SUBUNIT ADJUVANTED INFLUENZA VACCINE FOR CHILDREN VACCINATION: DOUBLE-BLIND RANDOMIZED CLINICAL TRIAL

    Directory of Open Access Journals (Sweden)

    S.M. Kharit

    2010-01-01

    Full Text Available This article presents the safety data for cell-derived inactivated subunit adjuvanted influenza vaccine «Grippol Neo» in children 3–17 years old in comparison with reference egg-derived inactivated subunit vaccine «Grippol plus». Good test vaccine tolerability and high efficacy profile is demonstrated. Based on the results obtained vaccine «Grippol Neo» is recommended for mass influenza prophylaxis in pediatry, including National Immunization Schedule.Key words: children, influenza, vaccination, «Grippol Neo».(Voprosy sovremennoi pediatrii — Current Pediatrics. – 2010;9(4:44-49

  18. Effect of different culture systems on the production of foot and mouth disease trivalent vaccine

    Directory of Open Access Journals (Sweden)

    Amr Ismail Hassan

    2016-01-01

    Full Text Available Aim: This study aims to determine the effect of the stationary rawx, roller, and the suspension cell culture systems on the total virus yield infectivity and antigenicity. Materials and Methods: Three serotypes of foot and mouth disease virus (FMDV (serotype A, O and SAT-2 were inoculated separately into baby hamster kidney-21 cell line in rawx, roller, and suspension cultivation systems using multiplicity of infection (1:100. Samples were taken from the total virus yield from each system at 15, 18, 21, and 24 h post-inoculation. Testing the total virus yield infectivity through virus titration and antigenicity through estimation of complement fixing titer and 146S content and evaluation of the potency of the vaccine prepared from the different cultivation systems were done. Results: The results showed that the FMDV titer of serotype A, O, and SAT-2 obtained from the roller cultivation system showed the highest level followed by suspension cultivation system then the rawx cultivation system. The FMDV titer showed its highest level at 21 h post-inoculation in all the cultivation systems and then decline at 24 h post-inoculation. The antigenicity reached its highest value content at 18 h post-inoculation either by complement fixation test or by quantifying the 146S intact virion. Montanide ISA 206 oil inactivated trivalent vaccines were prepared from the tested serotypes (A Iran O5. O Panasia and SAT-2/EGY/2012 harvested at 18 h post-inoculation from the 3 culture systems. The results of tracing the antibody response showed that the mean antibody response from the roller cultivation system start its protective antibody titer earlier at 2 weeks post-vaccination (WPV than the vaccine prepared from the other two cultivation system and the immune protection period lasts longer for 36 WPV for the roller cultivation system vaccine than the other two cultivation systems. Conclusion: The best cultivation system used for the production of FMD vaccine

  19. Comparison of the efficacy of a commercial inactivated influenza A/H1N1/pdm09 virus (pH1N1 vaccine and two experimental M2e-based vaccines against pH1N1 challenge in the growing pig model.

    Directory of Open Access Journals (Sweden)

    Tanja Opriessnig

    Full Text Available Swine influenza A viruses (IAV-S found in North American pigs are diverse and the lack of cross-protection among heterologous strains is a concern. The objective of this study was to compare a commercial inactivated A/H1N1/pdm09 (pH1N1 vaccine and two novel subunit vaccines, using IAV M2 ectodomain (M2e epitopes as antigens, in a growing pig model. Thirty-nine 2-week-old IAV negative pigs were randomly assigned to five groups and rooms. At 3 weeks of age and again at 5 weeks of age, pigs were vaccinated intranasally with an experimental subunit particle vaccine (NvParticle/M2e or a subunit complex-based vaccine (NvComplex/M2e or intramuscularly with a commercial inactivated vaccine (Inact/pH1N1. At 7 weeks of age, the pigs were challenged with pH1N1 virus or sham-inoculated. Necropsy was conducted 5 days post pH1N1 challenge (dpc. At the time of challenge one of the Inact/pH1N1 pigs had seroconverted based on IAV nucleoprotein-based ELISA, Inact/pH1N1 pigs had significantly higher pdm09H1N1 hemagglutination inhibition (HI titers compared to all other groups, and M2e-specific IgG responses were detected in the NvParticle/M2e and the NvComplex/M2e pigs with significantly higher group means in the NvComplex/M2e group compared to SHAMVAC-NEG pigs. After challenge, nasal IAV RNA shedding was significantly reduced in Inact/pH1N1 pigs compared to all other pH1N1 infected groups and this group also had reduced IAV RNA in oral fluids. The macroscopic lung lesions were characterized by mild-to-severe, multifocal-to-diffuse, cranioventral dark purple consolidated areas typical of IAV infection and were similar for NvParticle/M2e, NvComplex/M2e and SHAMVAC-IAV pigs. Lesions were significantly less severe in the SHAMVAC-NEG and the Inact/pH1N1pigs. Under the conditions of this study, a commercial Inact/pH1N1 specific vaccine effectively protected pigs against homologous challenge as evidenced by reduced clinical signs, virus shedding in nasal secretions and

  20. A combined Haemophilus influenzae type B Neisseria meningitidis serogroup C tetanus toxoid conjugate vaccine is immunogenic and well-tolerated when coadministered with diphtheria, tetanus, acellular pertussis hepatitis B-inactivated poliovirus at 3, 5 and 11 months of age: results of an open, randomized, controlled study.

    Science.gov (United States)

    Vesikari, Timo; Forstén, Aino; Desole, Maria Guiseppina; Ferrera, Giuseppe; Caubet, Magalie; Mesaros, Narcisa; Boutriau, Dominique

    2013-05-01

    This study evaluated the immunogenicity, reactogenicity and safety of the combined Haemophilus influenzae type B Neisseria meningitidis serogroup C tetanus toxoid conjugate vaccine (Hib-MenC-TT) coadministered with diphtheria, tetanus, acellular pertussis hepatitis B-inactivated poliovirus (DTPa-HBV-IPV) as 2 primary and 1 booster doses at 3, 5 and 11 months of age. In this phase III open study (NCT00327184), 709 infants were randomized in 2 parallel groups (1:1) to receive either Hib-MenC-TT coadministered with DTPa-HBV-IPV or control vaccines (MenC-TT coadministered with DTPa-HBV-IPV/Hib). Serum bactericidal activity for MenC (rSBA-MenC) and antibody concentrations against polyribosylribitol phosphate from Hib (anti-PRP) and hepatitis B (anti-HBs) were measured at 1 month after dose 2, before booster and 1 month after booster dose. Solicited (local/general) and unsolicited symptoms were assessed up to 4 and 31 days, respectively, after each vaccination. Serious adverse events were recorded throughout the study. One month after dose 2, high percentages of infants in both groups had rSBA-MenC titers ≥ 8 (≥ 99.1%), anti-PRP concentrations ≥ 0.15 μg/mL (≥ 96.5%) and anti-HBs concentrations ≥ 10 mIU/mL (≥ 95.3%), which persisted up to the booster vaccination (≥ 94.5%, ≥ 86.1%, ≥ 94.2%) and increased again after the booster dose (100%, 100%, ≥ 99%). Exploratory analyses indicated that rSBA-MenC geometric mean titers were lower and anti-PRP geometric mean concentrations were higher in the infants vaccinated with Hib-MenC-TT compared with the control vaccines at all time points. The safety profiles of the coadministered vaccines were similar in both groups. The Hib-MenC-TT and DTPa-HBV-IPV vaccines are immunogenic with a clinically acceptable safety profile when coadministered as 2 primary doses during infancy and 1 booster dose at 11 months of age.

  1. Establishment of pandemic influenza vaccine production capacity at Bio Farma, Indonesia.

    Science.gov (United States)

    Suhardono, Mahendra; Ugiyadi, Dori; Nurnaeni, Ida; Emelia, Imelda

    2011-07-01

    In Indonesia, avian influenza A(H5N1) virus started to spread in humans in June 2005, with an alarming case-fatality rate of more than 80%. Considering that global influenza vaccine production capacity would barely have covered 10% of the world's pandemic vaccine needs, and that countries with no production facilities or prearranged contracts would be without access to a vaccine, the Government of Indonesia embarked on a programme to increase its readiness for a future influenza pandemic. This included the domestic production of influenza vaccine, which was entrusted to Bio Farma. This health security strategy consists of developing trivalent influenza vaccine production capacity in order to be able to convert immediately to monovalent production of up to 20 million pandemic doses for the Indonesian market upon receipt of the seed strain from the World Health Organization (WHO). For this purpose, a dedicated production facility is being constructed within the Bio Farma premises in Bandung. As an initial stage of influenza vaccine development, imported seasonal influenza bulk has been formulated and filled in the Bio Farma facility. Following three consecutive batches and successful clinical trials, the product was licensed by the Indonesian National Regulatory Authority and distributed commercially for the Hajj programme in 2009. With continued support from its technology transfer partners, Bio Farma is now advancing with the development of upstream processes to produce its own bulk for seasonal and pandemic use. Copyright © 2011 Elsevier Ltd. All rights reserved.

  2. Development of Live-Attenuated Influenza Vaccines against Outbreaks of H5N1 Influenza

    Directory of Open Access Journals (Sweden)

    Yinglei Yi

    2012-12-01

    Full Text Available Several global outbreaks of highly pathogenic avian influenza (HPAI H5N1 virus have increased the urgency of developing effective and safe vaccines against H5N1. Compared with H5N1 inactivated vaccines used widely, H5N1 live-attenuated influenza vaccines (LAIVs have advantages in vaccine efficacy, dose-saving formula, long-lasting effect, ease of administration and some cross-protective immunity. Furthermore, H5N1 LAIVs induce both humoral and cellular immune responses, especially including improved IgA production at the mucosa. The current trend of H5N1 LAIVs development is toward cold-adapted, temperature-sensitive or replication-defective vaccines, and moreover, H5N1 LAIVs plus mucosal adjuvants are promising candidates. This review provides an update on the advantages and development of H5N1 live-attenuated influenza vaccines.

  3. Avian influenza

    Directory of Open Access Journals (Sweden)

    Tjandra Y. Aditama

    2006-06-01

    Full Text Available Avian influenza, or “bird flu”, is a contagious disease of animals which crossed the species barrier to infect humans and gave a quite impact on public health in the world since 2004, especially due to the threat of pandemic situation. Until 1st March 2006, laboratory-confirmed human cases have been reported in seven countries: Cambodia, Indonesia, Thailand, Viet Nam, China, Iraq and Turkey with a total of 174 cases and 94 dead (54.02%. Indonesia has 27 cases, 20 were dead (74.07%. AI cases in Indonesia are more in male (62.5% and all have a symptom of fever. An influenza pandemic is a rare but recurrent event. An influenza pandemic happens when a new subtype emerges that has not previously circulated in humans. For this reason, avian H5N1 is a strain with pandemic potential, since it might ultimately adapt into a strain that is contagious among humans. Impact of the pandemic could include high rates of illness and worker absenteeism are expected, and these will contribute to social and economic disruption. Historically, the number of deaths during a pandemic has varied greatly. Death rates are largely determined by four factors: the number of people who become infected, the virulence of the virus, the underlying characteristics and vulnerability of affected populations, and the effectiveness of preventive measures. Accurate predictions of mortality cannot be made before the pandemic virus emerges and begins to spread. (Med J Indones 2006; 15:125-8Keywords: Avian Influenza, Pandemic

  4. ADULT INFLUENZA VACCINATION GUIDELINE

    African Journals Online (AJOL)

    immunisation, and successful influenza vaccines are available each year for the predominant serotypes of the virus. 2. THE VIRUS2.6-9. The influenza viruses are enveloped viruses with a segmented. RNA genome. There are three types, influenza A, B and C based on antigenic differences. Both influenza A and B viruses.

  5. Baseline levels of influenza-specific CD4 memory T-cells affect T-cell responses to influenza vaccines.

    Science.gov (United States)

    He, Xiao-Song; Holmes, Tyson H; Sasaki, Sanae; Jaimes, Maria C; Kemble, George W; Dekker, Cornelia L; Arvin, Ann M; Greenberg, Harry B

    2008-07-02

    Factors affecting immune responses to influenza vaccines have not been studied systematically. We hypothesized that T-cell and antibody responses to the vaccines are functions of pre-existing host immunity against influenza antigens. During the 2004 and 2005 influenza seasons, we have collected data on cellular and humoral immune reactivity to influenza virus in blood samples collected before and after immunization with inactivated or live attenuated influenza vaccines in healthy children and adults. We first used cross-validated lasso regression on the 2004 dataset to identify a group of candidate baseline correlates with T-cell and antibody responses to vaccines, defined as fold-increase in influenza-specific T-cells and serum HAI titer after vaccination. The following baseline parameters were examined: percentages of influenza-reactive IFN-gamma(+) cells in T and NK cell subsets, percentages of influenza-specific memory B-cells, HAI titer, age, and type of vaccine. The candidate baseline correlates were then tested with the independent 2005 dataset. Baseline percentage of influenza-specific IFN-gamma(+) CD4 T-cells was identified as a significant correlate of CD4 and CD8 T-cell responses, with lower baseline levels associated with larger T-cell responses. Baseline HAI titer and vaccine type were identified as significant correlates for HAI response, with lower baseline levels and the inactivated vaccine associated with larger HAI responses. Previously we reported that baseline levels of CD56(dim) NK reactivity against influenza virus inversely correlated with the immediate T-cell response to vaccination, and that NK reactivity induced by influenza virus depended on IL-2 produced by influenza-specific memory T-cells. Taken together these results suggest a novel mechanism for the homeostasis of virus-specific T-cells, which involves interaction between memory helper T-cells, CD56(dim) NK and DC. These results demonstrate that assessment of baseline biomarkers may

  6. Baseline levels of influenza-specific CD4 memory T-cells affect T-cell responses to influenza vaccines.

    Directory of Open Access Journals (Sweden)

    Xiao-Song He

    Full Text Available BACKGROUND: Factors affecting immune responses to influenza vaccines have not been studied systematically. We hypothesized that T-cell and antibody responses to the vaccines are functions of pre-existing host immunity against influenza antigens. METHODOLOGY/PRINCIPAL FINDINGS: During the 2004 and 2005 influenza seasons, we have collected data on cellular and humoral immune reactivity to influenza virus in blood samples collected before and after immunization with inactivated or live attenuated influenza vaccines in healthy children and adults. We first used cross-validated lasso regression on the 2004 dataset to identify a group of candidate baseline correlates with T-cell and antibody responses to vaccines, defined as fold-increase in influenza-specific T-cells and serum HAI titer after vaccination. The following baseline parameters were examined: percentages of influenza-reactive IFN-gamma(+ cells in T and NK cell subsets, percentages of influenza-specific memory B-cells, HAI titer, age, and type of vaccine. The candidate baseline correlates were then tested with the independent 2005 dataset. Baseline percentage of influenza-specific IFN-gamma(+ CD4 T-cells was identified as a significant correlate of CD4 and CD8 T-cell responses, with lower baseline levels associated with larger T-cell responses. Baseline HAI titer and vaccine type were identified as significant correlates for HAI response, with lower baseline levels and the inactivated vaccine associated with larger HAI responses. Previously we reported that baseline levels of CD56(dim NK reactivity against influenza virus inversely correlated with the immediate T-cell response to vaccination, and that NK reactivity induced by influenza virus depended on IL-2 produced by influenza-specific memory T-cells. Taken together these results suggest a novel mechanism for the homeostasis of virus-specific T-cells, which involves interaction between memory helper T-cells, CD56(dim NK and DC

  7. School-located influenza vaccination decreases laboratory-confirmed influenza and improves school attendance.

    Science.gov (United States)

    Pannaraj, Pia S; Wang, Hai-Lin; Rivas, Hector; Wiryawan, Hilda; Smit, Michael; Green, Nicole; Aldrovandi, Grace M; El Amin, Alvin Nelson; Mascola, Laurene

    2014-08-01

    School-located influenza vaccination (SLV) programs can efficiently immunize large numbers of school-aged children. We evaluated the impact of SLV on laboratory-confirmed influenza and absenteeism. Active surveillance for influenza-like illness (ILI) was conducted on 4455 children in 4 SLV intervention and 4 control elementary schools (grades K-6) matched for sociodemographic characteristics during the 2010-2011 influenza season in Los Angeles County, California. Combined nose/throat swabs were collected from febrile children with ILI at presentation to the school nurse or during absenteeism. In SLV schools, 26.9%-46.6% of enrolled students received at least 1 dose of either inactivated or live attenuated influenza vaccine compared with 0.8%-4.3% in control schools. Polymerase chain reaction for respiratory viruses (PCR) was performed on 1021 specimens obtained from 898 children. Specimens were positive for influenza in 217 (21.3%), including 2009 H1N1 (30.9%), H3 (9.2%), and B (59.9%). Children attending SLV schools, regardless of vaccination status, were 30.8% (95% confidence interval, 10.1%-46.8%) less likely to acquire influenza compared with children at control schools. Unvaccinated children were indirectly protected in the school with nearly 50% vaccination coverage compared with control schools (influenza rate, 27.1 vs 60.0 per 1000 children; P = .023). Unvaccinated children missed more school days than vaccinated children (4.3 vs 2.8 days per 100 school days; P attendance. Herd immunity for unvaccinated children may occur in schools with vaccination coverage approaching 50%. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  8. Exceptional influenza morbidity in summer season of 2017 in Israel may predict the vaccine efficiency in the coming winter.

    Science.gov (United States)

    Pando, Rakefet; Sharabi, Sivan; Mandelboim, Michal

    2018-03-07

    Influenza infections are the leading cause of respiratory viral infections worldwide, and are mostly common in the winter season. The seasonal influenza vaccine is currently the most effective preventive modality against influenza infection. Immediately following each winter season the World Health Organization (WHO) announces the vaccine composition for the following winter. Unexpectedly, during the summer of 2017, in Israel, we observed in hospitalized patients, an exceptionally high numbers of Influenza positive cases. The majority of the influenza B infections were caused by influenza B/Yamagata lineage, which did not circulate in Israel in the previous winter, and most of the influenza A infections were caused by influenza A/H3N2, a strain similar to the strain that circulated in Israel in the previous winter. We therefore predict that these two viruses will circulate in the coming winter of 2017/18 and that the trivalent vaccine, which includes antigenically different viruses will be inefficient. Copyright © 2018 Elsevier Ltd. All rights reserved.

  9. MPLEx: a method for simultaneous pathogen inactivation and extraction of samples for multi-omics profiling

    Energy Technology Data Exchange (ETDEWEB)

    Burnum-Johnson, Kristin E.; Kyle, Jennifer E.; Eisfeld, Amie J.; Casey, Cameron P.; Stratton, Kelly G.; Gonzalez, Juan F.; Habyarimana, Fabien; Negretti, Nicholas M.; Sims, Amy C.; Chauhan, Sadhana; Thackray, Larissa B.; Halfmann, Peter J.; Walters, Kevin B.; Kim, Young-Mo; Zink, Erika M.; Nicora, Carrie D.; Weitz, Karl K.; Webb-Robertson, Bobbie-Jo M.; Nakayasu, Ernesto S.; Ahmer, Brian; Konkel, Michael E.; Motin, Vladimir; Baric, Ralph S.; Diamond, Michael S.; Kawaoka, Yoshihiro; Waters, Katrina M.; Smith, Richard D.; Metz, Thomas O.

    2017-01-01

    The continued emergence and spread of infectious agents is of increasing concern due to increased population growth and the associated increased livestock production to meet food demands, increased urbanization and land-use changes, and greater travel. A systems biology approach to infectious disease research can significantly advance our understanding of host-pathogen relationships and facilitate the development of new therapies and vaccines. Molecular characterization of infectious samples outside of appropriate biosafety containment can only take place subsequent to pathogen inactivation. Herein, we describe a modified Folch extraction using chloroform/methanol that facilitates the molecular characterization of infectious samples by enabling simultaneous pathogen inactivation and extraction of proteins, metabolites, and lipids for subsequent mass spectrometry-based multi-omics measurements. This metabolite, protein and lipid extraction (MPLEx) method resulted in complete inactivation of bacterial and viral pathogens with exposed lipid membranes, including Yersinia pestis, Salmonella Typhimurium, and Campylobacter jejuni in pure culture, and Yersinia pestis, Campylobacter jejuni, West Nile, MERS-CoV, Ebola, and influenza H7N9 viruses in infection studies. Partial inactivation was observed for pathogens without exposed lipid membranes including 99.99% inactivation of community-associated methicillin-resistant Staphylococcus aureus, 99.6% and >99% inactivation of Clostridium difficile spores and vegetative cells, respectively, and 50% inactivation of adenovirus type 5. To demonstrate that MPLEx yields biomaterial of sufficient quality for subsequent multi-omics analyses, we highlight select proteomics, metabolomics and lipidomics data from human epithelial lung cells infected with wild-type and mutant forms of influenza H7N9. We believe that MPLEx will facilitate systems biology studies of infectious samples by enabling simultaneous pathogen inactivation and multi

  10. Fever following immunization with influenza A (H1N1) vaccine in children : a survey-based study in the Netherlands

    NARCIS (Netherlands)

    Broos, Nancy; van Puijenbroek, Eugène P; van Grootheest, Kees

    2010-01-01

    BACKGROUND: In November 2009, all children in the Netherlands from 6 months up to 4 years of age were indicated to receive the Influenza A (H1N1) vaccine. Fever is a common adverse event following immunization in children. Pandemrix®, an inactivated, split-virus influenza A (H1N1) vaccine, was used

  11. First-Principles Modeling of ThO2 Solid Solutions with Oxides of Trivalent Cations

    Science.gov (United States)

    Alexandrov, Vitaly; Asta, Mark; Gronbech-Jensen, Niels

    2010-03-01

    Solid solutions formed by doping ThO2 with oxides of trivalent cations, such as Y2O3 and La2O3, are suitable for solid electrolyte applications, similar to doped zirconia and ceria. ThO2 has also been gaining much attention as an alternative to UO2 in nuclear energy applications, the aforementioned trivalent cations being important fission products. In both cases the mixing energetics and short-range ordering/clustering are key to understanding structural and transport properties. Using first-principles atomistic calculations, we address intra- and intersublattice interactions for both cation and anion sublattices in ThO2-based fluorite-type solid solutions and compare the results with similar modeling studies for related trivalent-doped zirconia systems.

  12. 2015/16 I-MOVE/I-MOVE+ multicentre case-control study in Europe: Moderate vaccine effectiveness estimates against influenza A(H1N1)pdm09 and low estimates against lineage-mismatched influenza B among children.

    Science.gov (United States)

    Kissling, Esther; Valenciano, Marta; Pozo, Francisco; Vilcu, Ana-Maria; Reuss, Annicka; Rizzo, Caterina; Larrauri, Amparo; Horváth, Judit Krisztina; Brytting, Mia; Domegan, Lisa; Korczyńska, Monika; Meijer, Adam; Machado, Ausenda; Ivanciuc, Alina; Višekruna Vučina, Vesna; van der Werf, Sylvie; Schweiger, Brunhilde; Bella, Antonino; Gherasim, Alin; Ferenczi, Annamária; Zakikhany, Katherina; O Donnell, Joan; Paradowska-Stankiewicz, Iwona; Dijkstra, Frederika; Guiomar, Raquel; Lazar, Mihaela; Kurečić Filipović, Sanja; Johansen, Kari; Moren, Alain

    2017-11-10

    During the 2015/16 influenza season in Europe, the cocirculating influenza viruses were A(H1N1)pdm09 and B/Victoria, which was antigenically distinct from the B/Yamagata component in the trivalent influenza vaccine. We used the test-negative design in a multicentre case-control study in twelve European countries to measure 2015/16 influenza vaccine effectiveness (VE) against medically attended influenza-like illness (ILI) laboratory-confirmed as influenza. General practitioners swabbed a systematic sample of consulting ILI patients and a random sample of influenza-positive swabs was sequenced. We calculated adjusted VE against influenza A(H1N1)pdm09, A(H1N1)pdm09 genetic group 6B.1 and influenza B overall and by age group. We included 11 430 ILI patients, of which 2272 were influenza A(H1N1)pdm09 and 2901 were influenza B cases. Overall VE against influenza A(H1N1)pdm09 was 32.9% (95% CI: 15.5-46.7). Among those aged 0-14, 15-64 and ≥65 years, VE against A(H1N1)pdm09 was 31.9% (95% CI: -32.3 to 65.0), 41.4% (95% CI: 20.5-56.7) and 13.2% (95% CI: -38.0 to 45.3), respectively. Overall VE against influenza A(H1N1)pdm09 genetic group 6B.1 was 32.8% (95% CI: -4.1 to 56.7). Among those aged 0-14, 15-64 and ≥65 years, VE against influenza B was -47.6% (95% CI: -124.9 to 3.1), 27.3% (95% CI: -4.6 to 49.4) and 9.3% (95% CI: -44.1 to 42.9), respectively. Vaccine effectiveness (VE) against influenza A(H1N1)pdm09 and its genetic group 6B.1 was moderate in children and adults, and low among individuals ≥65 years. Vaccine effectiveness (VE) against influenza B was low and heterogeneous among age groups. More information on effects of previous vaccination and previous infection is needed to understand the VE results against influenza B in the context of a mismatched vaccine. © 2017 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

  13. Vaccines for preventing influenza in healthy adults.

    Science.gov (United States)

    Demicheli, Vittorio; Jefferson, Tom; Ferroni, Eliana; Rivetti, Alessandro; Di Pietrantonj, Carlo

    2018-02-01

    The consequences of influenza in adults are mainly time off work. Vaccination of pregnant women is recommended internationally. This is an update of a review published in 2014. Future updates of this review will be made only when new trials or vaccines become available. Observational data included in previous versions of the review have been retained for historical reasons but have not been updated due to their lack of influence on the review conclusions. To assess the effects (efficacy, effectiveness, and harm) of vaccines against influenza in healthy adults, including pregnant women. We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 12), MEDLINE (January 1966 to 31 December 2016), Embase (1990 to 31 December 2016), the WHO International Clinical Trials Registry Platform (ICTRP; 1 July 2017), and ClinicalTrials.gov (1 July 2017), as well as checking the bibliographies of retrieved articles. Randomised controlled trials (RCTs) or quasi-RCTs comparing influenza vaccines with placebo or no intervention in naturally occurring influenza in healthy individuals aged 16 to 65 years. Previous versions of this review included observational comparative studies assessing serious and rare harms cohort and case-control studies. Due to the uncertain quality of observational (i.e. non-randomised) studies and their lack of influence on the review conclusions, we decided to update only randomised evidence. The searches for observational comparative studies are no longer updated. Two review authors independently assessed trial quality and extracted data. We rated certainty of evidence for key outcomes (influenza, influenza-like illness (ILI), hospitalisation, and adverse effects) using GRADE. We included 52 clinical trials of over 80,000 people assessing the safety and effectiveness of influenza vaccines. We have presented findings from 25 studies comparing inactivated parenteral influenza vaccine against placebo or do-nothing control groups as the

  14. [Influenza vaccination. Effectiveness of current vaccines and future challenges].

    Science.gov (United States)

    Ortiz de Lejarazu, Raúl; Tamames, Sonia

    2015-01-01

    Seasonal influenza is an annual challenge for health-care systems, due to factors such as co-circulation of 2 influenza A subtypes jointly with 2 influenza B lineages; the antigenic drift of these virus, which eludes natural immunity, as well as immunity conferred by vaccination; together with influenza impact in terms of morbidity and mortality. Influenza vaccines have been available for more than 70 years and they have progressed in formulation, production and delivery route. Recommendations on vaccination are focused on those with a higher probability of severe disease, and have a progressively wider coverage, and classically based on inactivated vaccines, but with an increasing importance of attenuated live vaccines. More inactivated vaccines are becoming available, from adyuvanted and virosomal vaccines to intradermal delivery, cell-culture or quadrivalent. Overall vaccine effectiveness is about 65%, but varies depending on characteristics of vaccines, virus, population and the outcomes to be prevented, and ranges from less than 10% to almost 90%. Future challenges are formulations that confer more extensive and lasting protection, as well as increased vaccination coverage, especially in groups such as pregnant women and health-care professionals, as well as being extended to paediatrics. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  15. Interactions between alpha-latrotoxin and trivalent cations in rat striatal synaptosomal preparations

    Energy Technology Data Exchange (ETDEWEB)

    Scheer, H.W.

    1989-05-01

    The interactions between alpha-latrotoxin (alpha-LTx), a neurosecretagogue purified from the venom of the black widow spider, and the trivalent cations Al3+, Y3+, La3+, Gd3+, and Yb3+ were investigated in rat striatal synaptosomal preparations. All trivalent cations tested were inhibitors of alpha-LTx-induced (/sup 3/H)dopamine ((/sup 3/H)DA) release (order of potency: Yb3+ greater than Gd3+ approximately Y3+ greater than La3+ greater than Al3+). Only with Al3+ could inhibition of (/sup 3/H)DA release be attributed to a block of /sup 125/I-alpha-LTx specific binding to synaptosomal preparations. The inhibitory effect of trivalent ions was reversible provided synaptosomes were washed with buffer containing EDTA. Trivalent ions also inhibited alpha-LTx-induced (/sup 3/H)DA release at times when alpha-LTx-stimulated release was already evident. alpha-LTx-induced synaptosomal membrane depolarization was blocked by La3+, but not affected by Gd3+, Y3+, and Yb3+. alpha-LTx-stimulated uptake of /sup 45/Ca/sup 2 +/ was inhibited by all trivalent cations tested. These results demonstrate that there exist at least three means by which trivalent cations can inhibit alpha-LTx action in rat striatal synaptosomal preparations: (1) inhibition of alpha-LTx binding (Al3+); (2) inhibition of alpha-LTx-induced depolarization (La3+); and (3) inhibition of alpha-LTx-induced /sup 45/Ca/sup 2 +/ uptake (Gd3+, Y3+, Yb3+, La3+).

  16. Sublingual vaccination with influenza virus protects mice against lethal viral infection

    Science.gov (United States)

    Song, Joo-Hye; Nguyen, Huan H.; Cuburu, Nicolas; Horimoto, Taisuke; Ko, Sung-Youl; Park, Se-Ho; Czerkinsky, Cecil; Kweon, Mi-Na

    2008-01-01

    We assessed whether the sublingual (s.l.) route would be an effective means of delivering vaccines against influenza virus in mice by using either formalin-inactivated or live influenza A/PR/8 virus (H1N1). Sublingual administration of inactivated influenza virus given on two occasions induced both systemic and mucosal antibody responses and conferred protection against a lethal intranasal (i.n.) challenge with influenza virus. Coadministration of a mucosal adjuvant (mCTA-LTB) enhanced these responses and resulted in complete protection against respiratory viral challenge. In addition, s.l. administration of formalin-inactivated A/PR/8 plus mCTA-LTB induced systemic expansion of IFN-γ-secreting T cells and virus-specific cytotoxic T lymphocyte responses. Importantly, a single s.l. administration of live A/PR/8 virus was not pathogenic and induced protection mediated by both acquired and innate immunity. Moreover, s.l. administration of live A/PR/8 virus conferred heterosubtypic protection against respiratory challenge with H3N2 virus. Unlike the i.n. route, the A/PR/8 virus, whether live or inactivated, did not migrate to or replicate in the CNS after s.l. administration. Based on these promising findings, we propose that the s.l. mucosal route offers an attractive alternative to mucosal routes for administering influenza vaccines. PMID:18227512

  17. Heterosybtypic T-cell immunity to influenza in humans: challenges for universal T-cell influenza vaccines

    Directory of Open Access Journals (Sweden)

    Saranya eSridhar

    2016-05-01

    Full Text Available Influenza A virus (IAV remains a significant global health issue causing annual epidemics, pandemics and sporadic human infections with highly pathogenic avian or swine influenza viruses. Current inactivated and live vaccines are the mainstay of the public health response to influenza although vaccine efficacy is lower against antigenically distinct viral strains. The first pandemic of the 21st century underlined the urgent need to develop new vaccines capable of protection against a broad range of influenza strains. Such universal influenza vaccines are based on the idea of heterosubtypic immunity wherein immune responses to epitopes conserved across IAV strains can confer protection against subsequent infection and disease. T-cells recognising conserved antigens are a key contributor to reducing viral load and limiting disease severity during heterosubtypic infection in animal models. Recent studies undertaken during the 2009 H1N1 pandemic provided key insights into the role of cross-reactive T-cells in mediating heterosubtypic protection in humans. This review focuses on human influenza to discuss the epidemiological observations that underpin cross-protective immunity, the role of T-cells as key players in mediating heterosubtypic immunity including recent data from natural history cohort studies and the ongoing clinical development of T-cell inducing universal influenza vaccines. The challenges and knowledge gaps for developing vaccines to generate long-lived protective T-cell responses is discussed.

  18. Efficacy of influenza vaccination and tamiflu® treatment--comparative studies with Eurasian Swine influenza viruses in pigs.

    Science.gov (United States)

    Duerrwald, Ralf; Schlegel, Michael; Bauer, Katja; Vissiennon, Théophile; Wutzler, Peter; Schmidtke, Michaela

    2013-01-01

    Recent epidemiological developments demonstrated that gene segments of swine influenza A viruses can account for antigenic changes as well as reduced drug susceptibility of pandemic influenza A viruses. This raises questions about the efficacy of preventive measures against swine influenza A viruses. Here, the protective effect of vaccination was compared with that of prophylactic Tamiflu® treatment against two Eurasian swine influenza A viruses. 11-week-old pigs were infected by aerosol nebulisation with high doses of influenza virus A/swine/Potsdam/15/1981 (H1N1/1981, heterologous challenge to H1N1 vaccine strain) and A/swine/Bakum/1832/2000 (H1N2/2000, homologous challenge to H1N2 vaccine strain) in two independent trials. In each trial (i) 10 pigs were vaccinated twice with a trivalent vaccine (RESPIPORC® FLU3; 28 and 7 days before infection), (ii) another 10 pigs received 150 mg/day of Tamiflu® for 5 days starting 12 h before infection, and (iii) 12 virus-infected pigs were left unvaccinated and untreated and served as controls. Both viruses replicated efficiently in porcine respiratory organs causing influenza with fever, dyspnoea, and pneumonia. Tamiflu® treatment as well as vaccination prevented clinical signs and significantly reduced virus shedding. Whereas after homologous challenge with H1N2/2000 no infectious virus in lung and hardly any lung inflammation were detected, the virus titre was not and the lung pathology was only partially reduced in H1N1/1981, heterologous challenged pigs. Tamiflu® application did not affect these study parameters. In conclusion, all tested preventive measures provided protection against disease. Vaccination additionally prevented virus replication and histopathological changes in the lung of homologous challenged pigs.

  19. Efficacy of Influenza Vaccination and Tamiflu® Treatment – Comparative Studies with Eurasian Swine Influenza Viruses in Pigs

    Science.gov (United States)

    Duerrwald, Ralf; Schlegel, Michael; Bauer, Katja; Vissiennon, Théophile; Wutzler, Peter; Schmidtke, Michaela

    2013-01-01

    Recent epidemiological developments demonstrated that gene segments of swine influenza A viruses can account for antigenic changes as well as reduced drug susceptibility of pandemic influenza A viruses. This raises questions about the efficacy of preventive measures against swine influenza A viruses. Here, the protective effect of vaccination was compared with that of prophylactic Tamiflu® treatment against two Eurasian swine influenza A viruses. 11-week-old pigs were infected by aerosol nebulisation with high doses of influenza virus A/swine/Potsdam/15/1981 (H1N1/1981, heterologous challenge to H1N1 vaccine strain) and A/swine/Bakum/1832/2000 (H1N2/2000, homologous challenge to H1N2 vaccine strain) in two independent trials. In each trial (i) 10 pigs were vaccinated twice with a trivalent vaccine (RESPIPORC® FLU3; 28 and 7 days before infection), (ii) another 10 pigs received 150 mg/day of Tamiflu® for 5 days starting 12 h before infection, and (iii) 12 virus-infected pigs were left unvaccinated and untreated and served as controls. Both viruses replicated efficiently in porcine respiratory organs causing influenza with fever, dyspnoea, and pneumonia. Tamiflu® treatment as well as vaccination prevented clinical signs and significantly reduced virus shedding. Whereas after homologous challenge with H1N2/2000 no infectious virus in lung and hardly any lung inflammation were detected, the virus titre was not and the lung pathology was only partially reduced in H1N1/1981, heterologous challenged pigs. Tamiflu® application did not affect these study parameters. In conclusion, all tested preventive measures provided protection against disease. Vaccination additionally prevented virus replication and histopathological changes in the lung of homologous challenged pigs. PMID:23630601

  20. Efficacy of influenza vaccination and tamiflu® treatment--comparative studies with Eurasian Swine influenza viruses in pigs.

    Directory of Open Access Journals (Sweden)

    Ralf Duerrwald

    Full Text Available Recent epidemiological developments demonstrated that gene segments of swine influenza A viruses can account for antigenic changes as well as reduced drug susceptibility of pandemic influenza A viruses. This raises questions about the efficacy of preventive measures against swine influenza A viruses. Here, the protective effect of vaccination was compared with that of prophylactic Tamiflu® treatment against two Eurasian swine influenza A viruses. 11-week-old pigs were infected by aerosol nebulisation with high doses of influenza virus A/swine/Potsdam/15/1981 (H1N1/1981, heterologous challenge to H1N1 vaccine strain and A/swine/Bakum/1832/2000 (H1N2/2000, homologous challenge to H1N2 vaccine strain in two independent trials. In each trial (i 10 pigs were vaccinated twice with a trivalent vaccine (RESPIPORC® FLU3; 28 and 7 days before infection, (ii another 10 pigs received 150 mg/day of Tamiflu® for 5 days starting 12 h before infection, and (iii 12 virus-infected pigs were left unvaccinated and untreated and served as controls. Both viruses replicated efficiently in porcine respiratory organs causing influenza with fever, dyspnoea, and pneumonia. Tamiflu® treatment as well as vaccination prevented clinical signs and significantly reduced virus shedding. Whereas after homologous challenge with H1N2/2000 no infectious virus in lung and hardly any lung inflammation were detected, the virus titre was not and the lung pathology was only partially reduced in H1N1/1981, heterologous challenged pigs. Tamiflu® application did not affect these study parameters. In conclusion, all tested preventive measures provided protection against disease. Vaccination additionally prevented virus replication and histopathological changes in the lung of homologous challenged pigs.

  1. Contribution of Vaccine-Induced Immunity toward either the HA or the NA Component of Influenza Viruses Limits Secondary Bacterial Complications▿

    OpenAIRE

    Huber, Victor C.; Peltola, Ville; Iverson, Amy R.; McCullers, Jonathan A.

    2010-01-01

    Secondary bacterial infections contribute to morbidity and mortality from influenza. Vaccine effectiveness is typically assessed using prevention of influenza, not secondary infections, as an endpoint. We vaccinated mice with formalin-inactivated influenza virus vaccine preparations containing disparate HA and NA proteins and demonstrated an ability to induce the appropriate anti-HA and anti-NA immune profiles. Protection from both primary viral and secondary bacterial infection was demonstra...

  2. Effectiveness of the 2013 and 2014 Southern Hemisphere Influenza Vaccines Against Laboratory-Confirmed Influenza in Young Children Using a Test-Negative Design, Bangkok, Thailand

    Science.gov (United States)

    Kittikraisak, Wanitchaya; Suntarattiwong, Piyarat; Ditsungnoen, Darunee; Klungthong, Chonticha; Fernandez, Stefan; Yoon, In-Kyu; Lindblade, Kim; Dawood, Fatimah S.; Olsen, Sonja J.; Chotpitayasunondh, Tawee

    2016-01-01

    Background The Thai Advisory Committee on Immunization Practices recommends annual influenza vaccination for children six months through two years of age, although older children may be vaccinated on request. We evaluated effectiveness of the 2013 and 2014 inactivated influenza vaccines to reduce medically-attended laboratory-confirmed influenza illness among Thai children aged 7–60 months. Methods From September 2013–May 2015, children with influenza-like illness (ILI) were screened with a rapid influenza diagnostic test. Enrolled children had nasal and throat swabs tested for influenza viruses using polymerase chain reaction (PCR). Cases and controls were subjects testing positive and negative, respectively, for influenza viruses by PCR. Vaccination status was ascertained from vaccination cards. Vaccine effectiveness (VE) was calculated as 100%*(1−odds ratio of vaccination among cases versus controls). Results Of 1,377 children enrolled, cases (n=490) and controls (n=887) were similar in demographic characteristics. Cases were less likely to receive influenza vaccine than controls in 2013 (6% vs. 14%; p=0.02), but not in 2014 (6% vs. 7%; p=0.57). Among cases, 126 (26%) were positive for influenza A(H1N1)pdm09 virus, 239 (49%) for influenza A(H3N2) and 124 (25%) for influenza B. One specimen was positive for both influenza A(H3N2) and B viruses. VE for full vaccination against all viruses was 64% (95% confidence interval [CI], 21%, 84%) in 2013 and 26% (95% CI, −47%, 63%) in 2014. Conclusions Influenza vaccination was low among Thai children in our study, and VE varied by year, highlighting the need for annual monitoring of VE to better understand vaccine program effectiveness. PMID:27307102

  3. Local innate and adaptive immune responses regulate inflammatory cell influx into the lungs after vaccination with formalin inactivated RSV

    NARCIS (Netherlands)

    Kruijsen, Debby; Schijf, Marcel A.; Lukens, Michaël V.; van Uden, Nathalie O.; Kimpen, Jan L.; Coenjaerts, Frank E.; van Bleek, Grada M.

    2011-01-01

    Inactivated respiratory syncytial virus (RSV) vaccines tend to predispose for immune mediated enhanced disease, characterized by Th2 responses and airway hypersensitivity reactions. We show in a C57BL/6 mouse model that the early innate response elicited by the challenge virus (RSV versus influenza

  4. Chalcogenides formed by trivalent rare earth elements with d-elements

    International Nuclear Information System (INIS)

    Flao, Zh.; Laruehl', P.; Olitro, R.

    1981-01-01

    Data on ternary compounds formed by trivalent rare earth elements with 3d-, 4d- and 5d-elements of the Periodic system is presented. Compounds of 3d-elements both in bivalent and trivalent states are considered. The main attention is paid to the structure of the compounds. Description of a great number of new structural types of compounds is given. In certain cases the structure has not been deciphered and, besides, structural investigations with monocrystals are not numerous. Attention is drawn to the existence of nonstoichiometric compounds. References to the works on investigation of thermal (melting temperature), magnetic, optical and electric properties as well as Moessbauer effect are presented

  5. Interim estimates of the effectiveness of influenza vaccination against influenza-associated hospitalization in children in Hong Kong, 2015-16.

    Science.gov (United States)

    Cowling, Benjamin J; Kwan, Mike Y W; Wong, Joshua S C; Feng, Shuo; Leung, Chi-Wai; Chan, Eunice L Y; Chan, Kwok-Hung; Ng, Tak-Keung; To, Wing-Kin; Peiris, Malik J S; Chiu, Susan S

    2017-01-01

    From 1 September 2015 through 31 January 2016, we enrolled 2068 children 6 months to 17 years of age admitted to hospital with a febrile acute respiratory infection in our test-negative study. Information on receipt of 2015-16 northern hemisphere inactivated influenza vaccination was elicited from parents or legal guardians. Using conditional logistic regression adjusting for age and matching on calendar time, we estimated influenza vaccine effectiveness against hospitalization with influenza A or B to be 79.2% (95% confidence interval: 42.0%-92.4%). Annual influenza vaccination should be more widely used in children in Hong Kong. © 2016 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

  6. Safety, immunogenicity and infectivity of new live attenuated influenza vaccines.

    Science.gov (United States)

    Isakova-Sivak, Irina; Rudenko, Larisa

    2015-01-01

    Live attenuated influenza vaccines (LAIVs) are believed to be immunologically superior to inactivated influenza vaccines, because they can induce a variety of adaptive immune responses, including serum antibodies, mucosal and cell-mediated immunity. In addition to the licensed cold-adapted LAIV backbones, a number of alternative LAIV approaches are currently being developed and evaluated in preclinical and clinical studies. This review summarizes recent progress in the development and evaluation of LAIVs, with special attention to their safety, immunogenicity and infectivity for humans, and discusses their perspectives for the future.

  7. Gamma-irradiated influenza A virus can prime for a cross-reactive and cross-protective immune response against influenza A viruses

    International Nuclear Information System (INIS)

    Mullbacher, A.; Ada, G.L.; Tha Hla, R.

    1988-01-01

    A-strain influenza virus A/JAP (H2N2) was tested for its ability to induce cytotoxic T cells (Tc) after being rendered non-infectious by either UV or gamma irradiation. Gamma-irradiated virus proved to be more efficient than UV-inactivated virus in priming for a memory Tc cell response or in boosting memory spleen cells in vitro. Most importantly, γ-inactivated, but not UV-inactivated, A/JAP immunized animals survived lethal challenge with heterologous (A/PC(H3N2), A/WSN(H1N1)) virus as effectively as mice primed with infectious virus

  8. Capture of cell culture-derived influenza virus by lectins: strain independent, but host cell dependent.

    Science.gov (United States)

    Opitz, Lars; Zimmermann, Anke; Lehmann, Sylvia; Genzel, Yvonne; Lübben, Holger; Reichl, Udo; Wolff, Michael W

    2008-12-01

    Strategies to control influenza outbreaks are focused mainly on prophylactic vaccination. Human influenza vaccines are trivalent blends of different virus subtypes. Therefore and due to frequent antigenic drifts, strain independent manufacturing processes are required for vaccine production. This study verifies the strain independency of a capture method based on Euonymus europaeus lectin-affinity chromatography (EEL-AC) for downstream processing of influenza viruses under various culture conditions propagated in MDCK cells. A comprehensive lectin binding screening was conducted for two influenza virus types from the season 2007/2008 (A/Wisconsin/67/2005, B/Malaysia/2506/2004) including a comparison of virus-lectin interaction by surface plasmon resonance technology. EEL-AC resulted in a reproducible high product recovery rate and a high degree of contaminant removal in the case of both MDCK cell-derived influenza virus types demonstrating clearly the general applicability of EEL-AC. In addition, host cell dependency of EEL-AC was studied with two industrial relevant cell lines: Vero and MDCK cells. However, the choice of the host cell lines is known to lead to different product glycosylation profiles. Hence, altered lectin specificities have been observed between the two cell lines, requiring process adaptations between different influenza vaccine production systems.

  9. The Possible Impact of Vaccination for Seasonal Influenza on Emergence of Pandemic Influenza via Reassortment.

    Directory of Open Access Journals (Sweden)

    Xu-Sheng Zhang

    Full Text Available One pathway through which pandemic influenza strains might emerge is reassortment from coinfection of different influenza A viruses. Seasonal influenza vaccines are designed to target the circulating strains, which intuitively decreases the prevalence of coinfection and the chance of pandemic emergence due to reassortment. However, individual-based analyses on 2009 pandemic influenza show that the previous seasonal vaccination may increase the risk of pandemic A(H1N1 pdm09 infection. In view of pandemic influenza preparedness, it is essential to understand the overall effect of seasonal vaccination on pandemic emergence via reassortment.In a previous study we applied a population dynamics approach to investigate the effect of infection-induced cross-immunity on reducing such a pandemic risk. Here the model was extended by incorporating vaccination for seasonal influenza to assess its potential role on the pandemic emergence via reassortment and its effect in protecting humans if a pandemic does emerge. The vaccination is assumed to protect against the target strains but only partially against other strains. We find that a universal seasonal vaccine that provides full-spectrum cross-immunity substantially reduces the opportunity of pandemic emergence. However, our results show that such effectiveness depends on the strength of infection-induced cross-immunity against any novel reassortant strain. If it is weak, the vaccine that induces cross-immunity strongly against non-target resident strains but weakly against novel reassortant strains, can further depress the pandemic emergence; if it is very strong, the same kind of vaccine increases the probability of pandemic emergence.Two types of vaccines are available: inactivated and live attenuated, only live attenuated vaccines can induce heterosubtypic immunity. Current vaccines are effective in controlling circulating strains; they cannot always help restrain pandemic emergence because of the

  10. Parental views on vaccine safety and future vaccinations of children who experienced an adverse event following routine or seasonal influenza vaccination in 2010.

    Science.gov (United States)

    Parrella, Adriana; Gold, Michael; Marshall, Helen; Braunack-Mayer, Annette; Watson, Maureen; Baghurst, Peter

    2012-05-01

    To assess parental vaccine safety views and future vaccination decisions after an adverse event following immunization (AEFI) experienced by their child. A cross-sectional telephone survey was conducted of parents of children aged 0-7 y, identified in AEFI reports submitted to the South Australian Immunization Section, Department Health. The reports included childhood National Immunization Program (NIP), seasonal or pandemic influenza vaccines. Interviews were conducted following a national suspension of the 2010 seasonal trivalent influenza (STIV) vaccine. Parental attitudes toward vaccine safety, reasons for reporting the AEFI and impact on future vaccination intent were assessed. Of 179 parents interviewed, 88% were confident in the safety of vaccines in general. Parents reporting an AEFI to the STIV were more likely to state the event had influenced future vaccination decisions than the NIP vaccine reporters (65% vs 14%, p vaccinate their children against influenza. Media reports of the 2010 STIV program suspension was the most common reason for reporting an AEFI for parents of children who received an influenza vaccination. The AEFI experience did not impact on parental decision to continue with routine childhood NIP schedules, regardless of whether children received influenza or NIP vaccines. In contrast, most parents whose child experienced an AEFI to the 2010 STIV stated decreased confidence in the safety of influenza vaccines, which is likely to have impacted on the uptake of seasonal influenza vaccination in 2011. Addressing influenza vaccine safety concerns to promote influenza vaccination in the community is required.

  11. Influenza (Flu) Viruses

    Science.gov (United States)

    ... and antigenic shift. Transmission of Influenza Viruses from Animals to People Influenza A viruses also are found in many different animals, including ducks, chickens, pigs, whales, horses and seals. ...

  12. Haemophilus Influenzae Type b

    Science.gov (United States)

    ... Text Size Email Print Share Haemophilus Influenzae type b Page Content Article Body If you’re like ... may have been unfamiliar with Haemophilus influenzae type b (Hib) infections until your pediatrician recommended a vaccine ...

  13. Metaphase I orientation of Robertsonian trivalents in the water-hyacinth grasshopper, Cornops aquaticum (Acrididae, Orthoptera

    Directory of Open Access Journals (Sweden)

    Pablo César Colombo

    2009-01-01

    Full Text Available Trivalents resulting from polymorphic Robertsonian rearrangements must have a regular orientation in metaphase I if the polymorphisms are to be maintained. It has been argued that redistribution of proximal and interstitial chiasmata to more distal positions is necessary for a convergent orientation, the only one that produces viable gametes. Cornops aquaticum is a South-American grasshopper that lives and feeds on water-hyacinths, and has three polymorphic Robertsonian rearrangements in its southernmost distribution area in Central Argentina and Uruguay. The orientation of trivalents in metaphase I, the formation of abnormal spermatids and the frequency and position of chiasmata in the trivalents, was analysed in a polymorphic population of C. aquaticus. In this study we observed a correlation between the number of trivalents with the frequency of abnormal spermatids; additionally, the number of chiasmata, especially proximal and interstitial ones, was strongly correlated with the frequency of the linear orientation. Therefore we confirmed our previous assumption, based on other evidence, that the chiasmata redistribution in fusion carriers is essential to the maintenance of the polymorphisms.

  14. Aging of trivalent metal hydroxide/oxide gels in divalent metal salt ...

    Indian Academy of Sciences (India)

    Unknown

    Aging of trivalent metal hydroxide/oxide gels in divalent metal salt solutions: Mechanism of formation of layered double hydroxides (LDHs). A V RADHA and P ..... This situation promotes coprecipitation of the two metal hydroxides, by virtue of which the titrations yield the. Zn–Al LDH. The LDHs isolated before and after ...

  15. METABOLISM AND TISSUE DOSIMETRY OF PENTAVALENT AND TRIVALENT MONOMETHYLATED ARSENIC AFTER ORAL

    Science.gov (United States)

    METABOLISM AND TISSUE DOSIMETRY OF PENTAVALENT AND TRIVALENT MONOMETHYLATED ARSENIC AFTER ORAL ADMINISTRATION IN MICEM F Hughes1, V Devesa2, B M Adair1, M Styblo2, E M Kenyon1, and D J Thomas1. 1US EPA, ORD, NHEERL, ETD, Research Triangle Park, NC; 2UNC-CH, CEMALB, Chapel Hi...

  16. Genotyping assay for differentiation of wild-type and vaccine viruses in subjects immunized with live attenuated influenza vaccine.

    Directory of Open Access Journals (Sweden)

    Victoria Matyushenko

    Full Text Available Live attenuated influenza vaccines (LAIVs are considered as safe and effective tool to control influenza in different age groups, especially in young children. An important part of the LAIV safety evaluation is the detection of vaccine virus replication in the nasopharynx of the vaccinees, with special attention to a potential virus transmission to the unvaccinated close contacts. Conducting LAIV clinical trials in some geographical regions with year-round circulation of influenza viruses warrants the development of robust and reliable tools for differentiating vaccine viruses from wild-type influenza viruses in nasal pharyngeal wash (NPW specimens of vaccinated subjects. Here we report the development of genotyping assay for the detection of wild-type and vaccine-type influenza virus genes in NPW specimens of young children immunized with Russian-backbone seasonal trivalent LAIV using Sanger sequencing from newly designed universal primers. The new primer set allowed amplification and sequencing of short fragments of viral genes in NPW specimens and appeared to be more sensitive than conventional real-time RT-PCR protocols routinely used for the detection and typing/subtyping of influenza virus in humans. Furthermore, the new assay is capable of defining the origin of wild-type influenza virus through BLAST search with the generated sequences of viral genes fragments.

  17. Avian Influenza in Birds

    Science.gov (United States)

    ... However, some ducks can be infected without any signs of illness. Top of Page Avian Influenza in Wild Birds Avian influenza A viruses have ... hours. Some ducks can be infected without any signs of illness. Avian influenza outbreaks are of concern in domesticated birds for ...

  18. Endocine™, N3OA and N3OASq; three mucosal adjuvants that enhance the immune response to nasal influenza vaccination.

    Directory of Open Access Journals (Sweden)

    Tina Falkeborn

    Full Text Available Annual outbreaks of seasonal influenza are controlled or prevented through vaccination in many countries. The seasonal vaccines used are either inactivated, currently administered parenterally, or live-attenuated given intranasally. In this study three mucosal adjuvants were examined for the influence on the humoral (mucosal and systemic and cellular influenza A-specific immune responses induced by a nasally administered vaccine. We investigated in detail how the anionic Endocine™ and the cationic adjuvants N3OA and N3OASq mixed with a split inactivated influenza vaccine induced influenza A-specific immune responses as compared to the vaccine alone after intranasal immunization. The study showed that nasal administration of a split virus vaccine together with Endocine™ or N3OA induced significantly higher humoral and cell-mediated immune responses than the non-adjuvanted vaccine. N3OASq only significantly increased the cell-mediated immune response. Furthermore, nasal administration of the influenza vaccine in combination with any of the adjuvants; Endocine™, N3OA or N3OASq, significantly enhanced the mucosal immunity against influenza HA protein. Thus the addition of these mucosal adjuvants leads to enhanced immunity in the most relevant tissues, the upper respiratory tract and the systemic circulation. Nasal influenza vaccination with an inactivated split vaccine can therefore provide an important mucosal immune response, which is often low or absent after traditional parenteral vaccination.

  19. Cross-protective immune responses elicited by live attenuated influenza vaccines.

    Science.gov (United States)

    Jang, Yo Han; Seong, Baik Lin

    2013-03-01

    The desired effect of vaccination is to elicit protective immune responses against infection with pathogenic agents. An inactivated influenza vaccine is able to induce the neutralizing antibodies directed primarily against two surface antigens, hemagglutinin and neuraminidase. These two antigens undergo frequent antigenic drift and hence necessitate the annual update of a new vaccine strain. Besides the antigenic drift, the unpredictable emergence of the pandemic influenza strain, as seen in the 2009 pandemic H1N1, underscores the development of a new influenza vaccine that elicits broadly protective immunity against the diverse influenza strains. Cold-adapted live attenuated influenza vaccines (CAIVs) are advocated as a more appropriate strategy for cross-protection than inactivated vaccines and extensive studies have been conducted to address the issues in animal models. Here, we briefly describe experimental and clinical evidence for cross-protection by the CAIVs against antigenically distant strains and discuss possible explanations for cross-protective immune responses afforded by CAIVs. Potential barriers to the achievement of a universal influenza vaccine are also discussed, which will provide useful guidelines for future research on designing an ideal influenza vaccine with broad protection without causing pathogenic effects such as autoimmunity or attrition of protective immunity against homologous infection.

  20. Vaccines for preventing influenza in people with asthma.

    Science.gov (United States)

    Cates, C J; Jefferson, T O; Rowe, B H

    2008-04-16

    exacerbations in the two weeks following influenza vaccination (Risk Difference 0.00; 95% confidence interval -0.02 to 0.02). Uncertainty remains about the degree of protection vaccination affords against asthma exacerbations that are related to influenza infection. Evidence from recently published trials indicates that there is no significant increase in asthma exacerbations immediately after vaccination (at least with inactivated influenza vaccination). There is concern regarding possible increased wheezing and hospital admissions in infants given live intranasal vaccination.

  1. Trivalent combination vaccine induces broad heterologous immune responses to norovirus and rotavirus in mice.

    Directory of Open Access Journals (Sweden)

    Kirsi Tamminen

    Full Text Available Rotavirus (RV and norovirus (NoV are the two major causes of viral gastroenteritis (GE in children worldwide. We have developed an injectable vaccine design to prevent infection or GE induced with these enteric viruses. The trivalent combination vaccine consists of NoV capsid (VP1 derived virus-like particles (VLPs of GI-3 and GII-4 representing the two major NoV genogroups and tubular RV recombinant VP6 (rVP6, the most conserved and abundant RV protein. Each component was produced in insect cells by a recombinant baculovirus expression system and combined in vitro. The vaccine components were administered intramuscularly to BALB/c mice either separately or in the trivalent combination. High levels of NoV and RV type specific serum IgGs with high avidity (>50% as well as intestinal IgGs were detected in the immunized mice. Cross-reactive IgG antibodies were also elicited against heterologous NoV VLPs not used for immunization (GII-4 NO, GII-12 and GI-1 VLPs and to different RVs from cell cultures. NoV-specific serum antibodies blocked binding of homologous and heterologous VLPs to the putative receptors, histo-blood group antigens, suggesting broad NoV neutralizing activity of the sera. Mucosal antibodies of mice immunized with the trivalent combination vaccine inhibited RV infection in vitro. In addition, cross-reactive T cell immune responses to NoV and RV-specific antigens were detected. All the responses were sustained for up to six months. No mutual inhibition of the components in the trivalent vaccine combination was observed. In conclusion, the NoV GI and GII VLPs combination induced broader cross-reactive and potentially neutralizing immune responses than either of the VLPs alone. Therefore, trivalent vaccine might induce protective immune responses to the vast majority of circulating NoV and RV genotypes.

  2. Do arsenosugars pose a risk to human health? The comparative toxicities of a trivalent and pentavalent arsenosugar.

    Science.gov (United States)

    Andrewes, Paul; Demarini, David M; Funasaka, Kunihiro; Wallace, Kathleen; Lai, Vivian W M; Sun, Hongsui; Cullen, William R; Kitchin, Kirk T

    2004-08-01

    Seafood frequently contains high concentrations of arsenic (approximately 10-100 mg/kg dry weight). In marine algae (seaweed), this arsenic occurs predominantly as ribose derivatives known collectively as arsenosugars. Although it is clear that arsenosugars are not acutely toxic, there is a possibility of arsenosugars having slight chronic toxicity. In general, trivalent arsenicals are more toxic than their pentavalent counterparts, so in this work we examine the hypothesis that trivalent arsenosugars might be significantly more toxic than pentavalent arsenosugars in vitro. We compared the in vitro toxicity of (R)-2,3-dihydroxypropyl-5-deoxy-5-dimethylarsinoyl-beta-D-riboside, a pentavalent arsenosugar, to that of its trivalent counterpart, (R)-2,3-dihydroxypropyl-5-deoxy-5-dimethylarsino-beta-D-riboside. The trivalent arsenosugar nicked plasmid DNA, whereas the pentavalent arsenosugar did not. The trivalent arsenosugar was more cytotoxic (IC50 = 200 microM, 48 h exposure) than its pentavalent counterpart (IC50 > 6000 microM, 48 h exposure) in normal human epidermal keratinocytes in vitro as determined via the neutral red uptake assay. However, both the trivalent and the pentavalent arsenosugars were significantly less toxic than MMA(III), DMA(III), and arsenate. Neither the pentavalent arsenosugar nor the trivalent arsenosugar were mutagenic in Salmonella TA104. The trivalent arsenosugar was readily formed by reaction of the pentavalent arsenosugar with thiol compounds, including, cysteine, glutathione, and dithioerythritol. This work suggests that the reduction of pentavalent arsenosugars to trivalent arsenosugars in biology might have environmental consequences, especially because seaweed consumption is a significant environmental source for human exposure to arsenicals.

  3. Immunogenicity and safety of a quadrivalent influenza vaccine in children and adolescents in Taiwan: A phase III open-label trial

    Directory of Open Access Journals (Sweden)

    Chun-Yi Lu

    2016-01-01

    Full Text Available Until recently, all seasonal influenza vaccines have been trivalent, containing strains A(H1N1, A(H3N2, and one of the two B strain lineages (Yamagata or Victoria, resulting in frequent mismatches between the circulating B strain lineage and that included in the vaccine. A quadrivalent, inactivated, split-virion influenza vaccine (IIV4 containing strains from both B lineages has been developed to address this. We performed an open-label phase III study to assess the immunogenicity and safety of the 2013–2014 Northern Hemisphere formulation of IIV4 in children and adolescents 9–17 years of age in Taiwan. Participants were vaccinated with one dose of IIV4 by intramuscular or deep subcutaneous injection. Hemagglutinin inhibition (HAI titers were measured before and 21 days after vaccination. Solicited injection-site and systemic reactions were assessed for up to 7 days after vaccination, and adverse events (AEs were recorded until day 21. One hundred participants were included. Despite relatively high pre-vaccination titers, post-vaccination HAI titers increased for all four strains, with geometric mean ratios (day 21/day 0 of 2.29 for A(H1N1, 2.05 for A(H3N2, 3.33 for B/Massachusetts (Yamagata lineage, and 4.59 for B/Brisbane (Victoria lineage. Post-vaccination seroprotection rates were 99% for A(H3N2 and 100% for A(H1N1, B/Massachusetts, and B/Brisbane. Due to high pre-vaccination titers, rates of seroconversion/significant increase of HAI titer were relatively low at 24% for A(H1N1, 20% for A(H3N2, 39% for B/Massachusetts, and 48% for B/Brisbane. Injection-site pain (56%, myalgia (45%, and malaise (15% were the most frequently reported solicited reactions, and most solicited reactions were mild or moderate. No treatment-related AEs, immediate unsolicited AEs, unsolicited non-serious injection-site AEs, grade 3 unsolicited AEs, or serious AEs were reported. In conclusion, this study showed that the 2013–2014 Northern Hemisphere

  4. Stabilization of influenza vaccine enhances protection by microneedle delivery in the mouse skin.

    Directory of Open Access Journals (Sweden)

    Fu-Shi Quan

    2009-09-01

    Full Text Available Simple and effective vaccine administration is particularly important for annually recommended influenza vaccination. We hypothesized that vaccine delivery to the skin using a patch containing vaccine-coated microneedles could be an attractive approach to improve influenza vaccination compliance and efficacy.Solid microneedle arrays coated with inactivated influenza vaccine were prepared for simple vaccine delivery to the skin. However, the stability of the influenza vaccine, as measured by hemagglutination activity, was found to be significantly damaged during microneedle coating. The addition of trehalose to the microneedle coating formulation retained hemagglutination activity, indicating stabilization of the coated influenza vaccine. For both intramuscular and microneedle skin immunization, delivery of un-stabilized vaccine yielded weaker protective immune responses including viral neutralizing antibodies, protective efficacies, and recall immune responses to influenza virus. Immunization using un-stabilized vaccine also shifted the pattern of antibody isotypes compared to the stabilized vaccine. Importantly, a single microneedle-based vaccination using stabilized influenza vaccine was found to be superior to intramuscular immunization in controlling virus replication as well as in inducing rapid recall immune responses post challenge.The functional integrity of hemagglutinin is associated with inducing improved protective immunity against influenza. Simple microneedle influenza vaccination in the skin produced superior protection compared to conventional intramuscular immunization. This approach is likely to be applicable to other vaccines too.

  5. CAF01 adjuvant increases the protection conferred by a commercially available influenza split vaccine in a ferret model

    DEFF Research Database (Denmark)

    Martel, Cyril; Jensen, Trine Hammer; Nielsen, Lars Peter

    The immunogenicity and efficacy of preventive vaccines against influenza are considered suboptimal and the development of novel influenza vaccination strategies is urgently needed. Commercially available trivalent split vaccines are known to elicit mainly a humoral immune response, whereas......, we compared the immune response in ferrets vaccinated with a commercial influenza split vaccine with the same vaccine mixed with the CAF01 adjuvant and furthermore used two recently circulating H1N1 viruses for the challenge of the animals. We investigated antibody levels in serum and nasal washes...... the induction of cell-mediated immune responses is negligible. Recently, a cationic liposomal adjuvant (dimethyldioctadecylammonium/trehalose 6,6’-dibehenate, CAF01) was developed, which was proven to enhance both humoral and cell-mediated immune responses of a number of vaccine candidates. In the current study...

  6. CAF01 adjuvant increases the protection conferred by a commercially available influenza split vaccine in a ferret model

    DEFF Research Database (Denmark)

    Martel, Cyril; Jensen, Trine Hammer; Nielsen, Lars Peter

    The immunogenicity and efficacy of preventive vaccines against influenza are considered suboptimal and the development of novel influenza vaccination strategies is urgently needed. Commercially available trivalent split vaccines are known to elicit mainly a humoral immune response, whereas...... the induction of cell-mediated immune responses is negligible. Recently, a cationic liposomal adjuvant (dimethyldioctadecylammonium/trehalose 6,6’-dibehenate, CAF01) was developed, which was proven to enhance both humoral and cell-mediated immune responses of a number of vaccine candidates. In the current study......, we compared the immune response in ferrets vaccinated with a commercial influenza split vaccine with the same vaccine mixed with the CAF01 adjuvant and furthermore used two recently circulating H1N1 viruses for the challenge of the animals. We investigated antibody levels in serum and nasal washes...

  7. False-positive result when a diphenylcarbazide spot test is used on trivalent chromium-passivated zinc surfaces

    DEFF Research Database (Denmark)

    Reveko, Valeriia; Lampert, Felix; Din, Rameez Ud

    2018-01-01

    A colorimetric 1,5-diphenylcarbazide (DPC)-based spot test can be used to identify hexavalent chromium on various metallic and leather surfaces. DPC testing on trivalent chromium-passivated zinc surfaces has unexpectedly given positive results in some cases, apparently indicating the presence...... was used for the initial detection of hexavalent chromium on new and 1-year-aged trivalent chromium-passivated zinc surfaces. Then, X-ray photoelectron spectroscopy (XPS) was performed for all samples. Results The DPC spot test indicated the presence of hexavalent chromium in aged, but not new, trivalent...

  8. Inactivation of carotenoid-producing and albino strains of Neurospora crassa by visible light, blacklight, and ultraviolet radiation

    International Nuclear Information System (INIS)

    Blanc, P.L.; Tuveson, R.W.; Sargent, M.L.

    1976-01-01

    Suspensions of Neurospora crassa conidia were inactivated by blacklight (BL) radiation (300 to 425 nm) in the absence of exogenous photosensitizing compounds. Carotenoid-containing wild-type conidia were less sensitive to BL radiation than albino conidia, showing a dose enhancement factor (DEF) of 1.2 for dose levels resulting in less than 10 percent survival. The same strains were about equally sensitive to shortwave ultraviolet (uv) inactivation. The kinetics of BL inactivation are similar to those of photodynamic inactivation by visible light in the presence of a photosensitizing dye (methylene blue). Only limited inactivation by visible light in the absence of exogenous photosensitizers was observed. BL and UV inactivations are probably caused by different mechanisms since wild-type conidia are only slightly more resistant to BL radiation (DEF = 1.2 at 1.0 percent survival) than are conidia from a uv-sensitive strain (upr-1, uvs-3). The BL-induced lethal lesions are probably not cyclobutyl pyrimidine dimers since BL-inactivated Haemophilus influenzae transforming deoxyribonucleic acid is not photoreactivated by N. crassa wild-type enzyme extracts, whereas uv-inactivated transforming deoxyribonucleic acid is photoreactivable with this treatment

  9. A dual vaccine against influenza & Alzheimer's disease failed to enhance anti-β-amyloid antibody responses in mice with pre-existing virus specific memory.

    Science.gov (United States)

    Davtyan, Hayk; Ghochikyan, Anahit; Hovakimyan, Armine; Davtyan, Arpine; Cadagan, Richard; Marleau, Annette M; Albrecht, Randy A; García-Sastre, Adolfo; Agadjanyan, Michael G

    2014-12-15

    Novel dual vaccine, WSN-Aβ(1-10), based on the recombinant influenza virus, expressing immunodominant B-cell epitope of β-amyloid, simultaneously induced therapeutically potent anti-Aβ and anti-influenza antibodies. In this study we showed that boosting of WSN-WT primed mice with WSN-Aβ(1-10) enhances anti-viral, but fails to induce anti-Aβ antibody responses. This inhibition is associated with expression of Aβ(1-10) within the context of an inactivated influenza virus vaccine. These results demonstrate that the use of an inactivated influenza virus as a carrier for AD vaccine may not be applicable due to the possible inhibition of anti-Aβ antibody response in individuals previously vaccinated or infected with influenza. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Efficacy of an influenza hemagglutinin-diphtheria toxoid conjugate vaccine in elderly nursing home subjects during an influenza outbreak.

    Science.gov (United States)

    Gravenstein, S; Drinka, P; Duthie, E H; Miller, B A; Brown, C S; Hensley, M; Circo, R; Langer, E; Ershler, W B

    1994-03-01

    To compare the efficacy of an influenza hemagglutinin-diphtheria toxoid conjugate vaccine with the commercially available influenza hemagglutinin-subunit vaccine in preventing influenza in older adults living in a nursing home. A prospective, randomized, double-blind vaccine trial with 5 months of follow-up after vaccination. Fourteen Wisconsin nursing homes. Nursing home residents at least 65 years old who were able to give informed consent and were free of malignancy and not receiving immunosuppressive therapy. Participants received, by intramuscular injection, 0.5 mL of a trivalent influenza vaccine containing 15 micrograms each of A/Leningrad/360/86 (H3N2), A/Taiwan/1/86 (H1N1), and B/Ann Arbor/1/86 (HA) or 0.5 mL of an influenza vaccine containing the same antigens conjugated to diphtheria toxoid (HA-D). Blood was obtained pre- and 1 month post-vaccination to assess for any vaccine-induced antibody titer change. Clinical surveillance for respiratory illness was performed twice weekly for 5 months. A record was kept of all signs and symptoms of new respiratory illness, and a viral culture and acute and convalescent sera were obtained. 204 participants received HA and 204 received HA-D. Both groups had similar baseline antibody levels to all influenza antigens. HA-D recipients seroconverted more frequently based on serum neutralizing activity (P < 0.05), had a greater increase in geometric mean titer (GMT), and sustained the increase in antibody titer longer than HA recipients. Vaccine hemagglutinin recall was greater in a subset of HA-D recipients as measured by lymphocyte proliferative assays (P < 0.05). During an outbreak of influenza A (H3N2 A/Shanghai/11/87-like and A/Victoria/7/87-like), fewer HA-D (29/195) than HA (43/204) recipients had laboratory-confirmed infection (P = 0.053), and, of these, fewer HA-D-treated subjects had lower respiratory tract involvement (5/29 HA-D and 17/43 HA) (P = 0.022). HA-D was more immunogenic in institutionalized elderly

  11. Silent spread of highly pathogenic Avian Influenza H5N1 virus amongst vaccinated commercial layers

    NARCIS (Netherlands)

    Poetri, O.N.; Boven, M.; Claassen, I.J.T.M.; Koch, G.; Wibawan, I.W.; Stegeman, A.; Broek, van den J.; Bouma, A.

    2014-01-01

    The aim of this study was to determine whether a single vaccination of commercial layer type chickens with an inactivated vaccine containing highly pathogenic avian influenza virus strain H5N1 A/chicken/Legok/2003, carried out on the farm, was sufficient to protect against infection with the

  12. 76 FR 79203 - Prospective Grant of Exclusive License: Veterinary Biological Products for Swine Influenza Vaccines

    Science.gov (United States)

    2011-12-21

    .... Sustained outbreaks of highly pathogenic influenza in animals increase the risk of reassortment and adaption... efficient and versatile than the conventional inactivated whole-virus vaccines; (b) Can be precisely...) Because they do not contain other viral proteins, a diagnostic test will enable vaccinated animals to be...

  13. Recombinant viral-vectored vaccines for the control of avian influenza in poultry

    Science.gov (United States)

    Vaccination is a commonly used tool for the control of both low pathogenic and highly pathogenic avian influenza viruses. Traditionally inactivated adjuvanted vaccines made from a low pathogenic field strain has been used for vaccination, but advances in molecular biology has allowed a number of di...

  14. Kinetics of lung lesion development and pro-inflammatory cytokine response in pigs with vaccine-associated enhanced respiratory disease induced by challenge with pandemic (2009) A/H1N1 influenza virus

    Science.gov (United States)

    The objective of this report was to characterize the enhanced clinical disease and lung lesions observed in pigs vaccinated with inactivated H1N2 swine delta-cluster influenza A virus and challenged with pandemic 2009 A/H1N1 human influenza virus. Eighty-four, six-week-old, crossbred pigs were rand...

  15. Flublok Seasonal Influenza (Flu) Vaccination

    Science.gov (United States)

    ... Vaccine Safety and Pregnant Women Febrile Seizures Following Vaccination Flu Vaccine and People with Egg Allergies Guillain- ... Flu Vaccines Quadrivalent Influenza Vaccine Intradermal Influenza (Flu) Vaccination Fluzone High-Dose Seasonal Influenza Vaccine Cell-Based ...

  16. Intranasal vaccination promotes detrimental Th17-mediated immunity against influenza infection.

    Directory of Open Access Journals (Sweden)

    Asher Maroof

    2014-01-01

    Full Text Available Influenza disease is a global health issue that causes significant morbidity and mortality through seasonal epidemics. Currently, inactivated influenza virus vaccines given intramuscularly or live attenuated influenza virus vaccines administered intranasally are the only approved options for vaccination against influenza virus in humans. We evaluated the efficacy of a synthetic toll-like receptor 4 agonist CRX-601 as an adjuvant for enhancing vaccine-induced protection against influenza infection. Intranasal administration of CRX-601 adjuvant combined with detergent split-influenza antigen (A/Uruguay/716/2007 (H3N2 generated strong local and systemic immunity against co-administered influenza antigens while exhibiting high efficacy against two heterotypic influenza challenges. Intranasal vaccination with CRX-601 adjuvanted vaccines promoted antigen-specific IgG and IgA antibody responses and the generation of polyfunctional antigen-specific Th17 cells (CD4(+IL-17A(+TNFα(+. Following challenge with influenza virus, vaccinated mice transiently exhibited increased weight loss and morbidity during early stages of disease but eventually controlled infection. This disease exacerbation following influenza infection in vaccinated mice was dependent on both the route of vaccination and the addition of the adjuvant. Neutralization of IL-17A confirmed a detrimental role for this cytokine during influenza infection. The expansion of vaccine-primed Th17 cells during influenza infection was also accompanied by an augmented lung neutrophilic response, which was partially responsible for mediating the increased morbidity. This discovery is of significance in the field of vaccinology, as it highlights the importance of both route of vaccination and adjuvant selection in vaccine development.

  17. Use of MgO doped with a divalent or trivalent metal cation for removing arsenic from water

    Science.gov (United States)

    Moore, Robert C; Holt-Larese, Kathleen C; Bontchev, Ranko

    2013-08-13

    Systems and methods for use of magnesium hydroxide, either directly or through one or more precursors, doped with a divalent or trivalent metal cation, for removing arsenic from drinking water, including water distribution systems. In one embodiment, magnesium hydroxide, Mg(OH).sub.2 (a strong adsorbent for arsenic) doped with a divalent or trivalent metal cation is used to adsorb arsenic. The complex consisting of arsenic adsorbed on Mg(OH).sub.2 doped with a divalent or trivalent metal cation is subsequently removed from the water by conventional means, including filtration, settling, skimming, vortexing, centrifugation, magnetic separation, or other well-known separation systems. In another embodiment, magnesium oxide, MgO, is employed, which reacts with water to form Mg(OH).sub.2. The resulting Mg(OH).sub.2 doped with a divalent or trivalent metal cation, then adsorbs arsenic, as set forth above. The method can also be used to treat human or animal poisoning with arsenic.

  18. Trivalent Chromium Process (TCP) as a Sealer for MIL-A-8625F Type II, IIB, and IC Anodic Coatings

    National Research Council Canada - National Science Library

    Matzdorf, Craig; Beck, Erin; Hilgeman, Amy; Prado, Ruben

    2008-01-01

    This report documents evaluations of trivalent chromium compositions (TCP) as sealers for MIL-A-8625F Type II, IIB, and IC anodic coatings conducted from March 2001 through December 2007 by Materials Engineering...

  19. Use of MgO doped with a divalent or trivalent metal cation for removing arsenic from water

    Energy Technology Data Exchange (ETDEWEB)

    Moore, Robert C.; Larese, Kathleen Caroline; Bontchev, Ranko Panayotov

    2017-05-30

    Systems and methods for use of magnesium hydroxide, either directly or through one or more precursors, doped with a divalent or trivalent metal cation, for removing arsenic from drinking water, including water distribution systems. In one embodiment, magnesium hydroxide, Mg(OH).sub.2 (a strong adsorbent for arsenic) doped with a divalent or trivalent metal cation is used to adsorb arsenic. The complex consisting of arsenic adsorbed on Mg(OH).sub.2 doped with a divalent or trivalent metal cation is subsequently removed from the water by conventional means, including filtration, settling, skimming, vortexing, centrifugation, magnetic separation, or other well-known separation systems. In another embodiment, magnesium oxide, MgO, is employed, which reacts with water to form Mg(OH).sub.2. The resulting Mg(OH).sub.2 doped with a divalent or trivalent metal cation, then adsorbs arsenic, as set forth above. The method can also be used to treat human or animal poisoning with arsenic.

  20. Live attenuated seasonal and pandemic influenza vaccine in school-age children: a randomized controlled trial.

    Science.gov (United States)

    Klick, Brendan; Durrani, Sunita; Chan, Kwok-Hung; Ip, Dennis K M; Chou, Erica S K; Kwok, Henry K H; Ng, Sophia; Chiu, Susan S; Peiris, J S Malik; Leung, Gabriel M; Cowling, Benjamin J

    2013-04-08

    The novel influenza A(H1N1pdm09) virus emerged in North America in early 2009 and rapidly spread worldwide. In this study we report the efficacy of the live attenuated monovalent H1N1pdm09 vaccine and 2009-10 seasonal influenza vaccine in a randomized double-blind placebo-controlled trial. We enrolled 703 children aged 7-11. Each child was randomly allocated in the ratio 3:2 to receive one dose of live attenuated monovalent H1N1pdm09 vaccine or saline placebo between November 2009 and January 2010, followed after 3-10 weeks by independent random allocation to one dose of live attenuated trivalent 2009-10 seasonal influenza vaccine or saline placebo in the same ratio. Children were followed up through September 2010 with biweekly telephone calls and symptom diaries. Seasonal and pandemic influenza infections were confirmed by virologic testing of nose and throat swabs collected during acute respiratory illnesses. Overall, 30 children had confirmed influenza including 3 (0.43%) H1N1pdm09, 10 (1.4%) seasonal A(H3N2), and 17 (2.4%) influenza B. There were no significant differences in incidence rates of H1N1pdm09 or A(H3N2) between the four study arms, but receipt of the seasonal influenza vaccine was associated with a significant reduction in risk of influenza B (pVaccine efficacy against confirmed H1N1pdm09 infection associated with receipt of the monovalent H1N1pdm09 vaccine was 65% (95% confidence interval, CI: -281%, 97%). Vaccine efficacies against confirmed seasonal influenza A(H3N2) and B infection associated with receipt of the seasonal influenza vaccine were 31% (95% CI: -138%, 80%) and 96% (95% CI: 67%, 99%) respectively. Vaccine efficacy was consistent with other studies of the monovalent H1N1pdm09 vaccine and seasonal influenza vaccines. Our study was underpowered to provide precise estimates of vaccine efficacy due to low incidence of influenza A viruses during the study period. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. Multi-Dimensional Measurement of Antibody-Mediated Heterosubtypic Immunity to Influenza.

    Directory of Open Access Journals (Sweden)

    Jiong Wang

    Full Text Available The human immune response to influenza vaccination depends in part on preexisting cross-reactive (heterosubtypic immunity from previous infection by, and/or vaccination with, influenza strains that share antigenic determinants with the vaccine strains. However, current methods for assessing heterosubtypic antibody responses against influenza, including the hemagglutination-inhibition (HAI assay and ELISA, are time and labor intensive, and require moderate amounts of serum and reagents. To address these issues we have developed a fluorescent multiplex assay, mPlex-Flu, that rapidly and simultaneously measures strain specific IgG, IgA, and IgM antibodies against influenza hemagglutinin (HA from multiple viral strains. We cloned, expressed and purified HA proteins from 12 influenza strains, and coupled them to multiplex beads. Assay validation showed that minimal sample volumes (<5 μl of serum were needed, and the assay had a linear response over a four Log10 range. The assay detected nanogram levels of anti-influenza specific antibodies, had high accuracy and reproducibility, with an average percentage coefficient of variation (%CV of 9.06 for intra-assay and 12.94 for inter-assay variability. Pre- and post-intramuscular trivalent influenza vaccination levels of virus specific Ig were consistent with HAI titer and ELISA measurements. A significant advantage of the mPLEX-Flu assay over the HAI assay is the ability to perform antigenic cartography, determining the antigenic distances between influenza HA's, without mathematical correction for HAI data issues. For validation we performed antigenic cartography on 14 different post-influenza infection ferret sera assayed against 12 different influenza HA's. Results were in good agreement with a phylogenetic tree generated from hierarchical clustering of the genomic HA sequences. This is the first report of the use of a multiplex method for antigenic cartography using ferret sera. Overall, the m

  2. Trivalent lanthanide/actinide separation in the spent nuclear fuel wastes' reprocessing

    International Nuclear Information System (INIS)

    Narbutt, J.; Krejzler, J.

    2006-01-01

    Separation of trivalent actinides, in particular americium and curium, from lanthanides is an important step in an advanced partitioning process for future reprocessing of spent nuclear fuels. Since the trivalent actinides and lanthanides have similar chemistries, it is rather difficult to separate them from each other. The aim of presented work was to study solvent extraction of Am(III) and Eu(III) in a system containing diethylhemi-BTP (6-(5,6-diethyl-1,2,4-triazin-3-yl)-2,2'-bipyridine) and COSAN (protonated bis(chlorodicarbollido)cobalt(III)). The system was chosen by several groups working in the integrated EC research Project EUROPART. Several physicochemical properties of the extraction system were analyzed and discussed

  3. A new incorporation mechanism for trivalent actinides into bioapatite: a TRLFS and EXAFS study.

    Science.gov (United States)

    Holliday, Kiel; Handley-Sidhu, Stephanie; Dardenne, Kathy; Renshaw, Joanna; Macaskie, Lynne; Walther, Clemens; Stumpf, Thorsten

    2012-02-28

    One of the most toxic byproducts of nuclear power and weapons production is the transuranics, which have a high radiotoxicity and long biological half-life due to their tendency to accumulate in the skeletal system. This accumulation is inhomogeneous and has been associated with the chemical properties and structure of the bone material rather than its location or function. This suggests a chemical driving force to incorporation and requires an atomic scale mechanistic understanding of the incorporation process. Here we propose a new incorporation mechanism for trivalent actinides and lanthanides into synthetic and biologically produced hydroxyapatite. Time-resolved laser fluorescence spectroscopy and extended X-ray absorption fine structure have been used to demonstrate that trivalent actinides and lanthanides incorporate into the amorphous grain boundaries of apatite. This incorporation site can be used to explain patterns in uptake and distribution of radionuclides in the mammalian skeletal system. © 2012 American Chemical Society

  4. Adsorption behaviors of trivalent actinides and lanthanides on pyridine resin in lithium chloride aqueous solution

    International Nuclear Information System (INIS)

    Tatsuya Suzuki

    2013-01-01

    The adsorption behaviors of trivalent actinides and lanthanides on pyridine resin in lithium chloride aqueous solution were investigated. The adsorbed amounts of lanthanides and the degree of mutual separation of lanthanides increased with an increase in the concentration of lithium chloride in aqueous solution. The group separation of the trivalent actinides and lanthanides was observed. This separation phenomenon is similar in a hydrochloric acid solution. However, the adsorption behavior of lanthanides in lithium chloride is different from their behavior in a hydrochloric acid solution. This fact shows that the adsorption mechanisms of lanthanides in a lithium chloride aqueous solution and in a hydrochloric acid solution are different; the adsorption mechanisms are attributed to the ion exchange in a hydrochloric acid solution, and to the complex formation with pyridine group in a lithium chloride solution. (author)

  5. Synergistic extraction of trivalent lanthanoids with 3-phenyl-4-benzoyl-5-isoxazolone and various sulphoxides

    International Nuclear Information System (INIS)

    Sahu, S.K.; Chakravortty, V.; Reddy, M.L.P.; Ramamohan, T.R.

    1999-01-01

    Synergistic extraction of trivalent lanthanoids Nd, Tb and Tm with mixtures of 3-phenyl-4-benzoyl-5-isoxazolone (HPBI) and dioctyl sulphoxide (DOSO), bis-2-ethylhexyl sulphoxide (B2EHSO) or diphenyl sulphoxide (DPhSO) in xylene from perchlorate solution was investigated. Lanthanoids were found to be extracted as Ln(PBI) 3 with HPBI alone. In the presence of sulphoxides, Nd(III) was found to be extracted as Nd(PBI) 3 . S and Nd(PBI) 3 . 2 S (where S = sulphoxide). On the other hand, Tb(III) and Tm(III) were extracted as Tb(PBI) 3 . S and Tm(PBI) 3 . S respectively. The equilibrium constants of the synergistic species were found to increase monotonically with decreasing ionic radii of these metal ions. The addition of a sulphoxide to the metal chelate system not only enhances the extraction efficiency but also improves the selectivities among these trivalent lanthanoids. (orig.)

  6. Solid bioneedle-delivered influenza vaccines are highly thermostable and induce both humoral and cellular immune responses.

    Directory of Open Access Journals (Sweden)

    Peter C Soema

    Full Text Available The potential of bioneedles to deliver influenza vaccines was investigated. Four influenza vaccine formulations were screened to determine the optimal formulation for use with bioneedles. The stability of the formulations after freeze-drying was checked to predict the stability of the influenza vaccines in the bioneedles. Subunit, split, virosomal and whole inactivated influenza (WIV vaccine were formulated and lyophilized in bioneedles, and subsequently administered to C57BL/6 mice. Humoral and cellular immune responses were assessed after vaccination. The thermostability of lyophilized vaccines was determined after one-month storage at elevated temperatures. Bioneedle influenza vaccines induced HI titers that are comparable to those induced by intramuscular WIV vaccination. Delivery by bioneedles did not alter the type of immune response induced by the influenza vaccines. Stability studies showed that lyophilized influenza vaccines have superior thermostability compared to conventional liquid vaccines, and remained stable after one-month storage at 60°C. Influenza vaccines delivered by bioneedles are a viable alternative to conventional liquid influenza vaccines. WIV was determined to be the most potent vaccine formulation for administration by bioneedles. Lyophilized influenza vaccines in bioneedles are independent of a cold-chain, due to their increased thermostability, which makes distribution and stockpiling easier.

  7. Tyrosinase inactivation in organic solvents.

    Science.gov (United States)

    Warrington, J C; Saville, B A

    1999-11-05

    The inactivation of the catecholase activity of mushroom tyrosinase was investigated under nonaqueous conditions. The enzyme was immobilized on glass beads, and assays were conducted in chloroform, toluene, amyl acetate, isopropyl ether, and butanol. The reaction components were pre-equilibrated for 2 weeks with a saturated salt solution at a water activity of 0.90. The initial reaction velocity varied between 1.3 x 10(3) mol product/((mol enzyme)(min)) in toluene and 8.7 x 10(3) mol product/((mol enzyme)(min)) in amyl acetate. The turnover number varied between 8.1 x 10(3) mol product/mol enzyme in toluene and 7.2 x 10(4) mol product/mol enzyme in amyl acetate. In each solvent, the tyrosinase reaction inactivation parameters were represented by a probabilistic model. Changes in the probability of inactivation were followed throughout the course of the reaction using a second model which relates the reaction velocity to the amount of product formed. These models reveal that the inactivation rate of tyrosinase decreases as the reaction progresses, and that the inactivation kinetics are independent of the quinone concentration in toluene, chloroform, butanol, and amyl acetate. Significant effects of quinone concentration were, however, observed in isopropyl ether. The likelihood of inactivation of the enzyme was found to be greatest toward the beginning of the reaction. In the latter phase of the reaction, inactivation probability was less and tended to remain constant until the completion of the reaction. Copyright 1999 John Wiley & Sons, Inc.

  8. Improved immunogenicity of individual influenza vaccine components delivered with a novel dissolving microneedle patch stable at room temperature.

    Science.gov (United States)

    Vassilieva, Elena V; Kalluri, Haripriya; McAllister, Devin; Taherbhai, Misha T; Esser, E Stein; Pewin, Winston P; Pulit-Penaloza, Joanna A; Prausnitz, Mark R; Compans, Richard W; Skountzou, Ioanna

    2015-08-01

    Prevention of seasonal influenza epidemics and pandemics relies on widespread vaccination coverage to induce protective immunity. In addition to a good antigenic match with the circulating viruses, the effectiveness of individual strains represented in the trivalent vaccines depends on their immunogenicity. In this study, we evaluated the immunogenicity of H1N1, H3N2, and B seasonal influenza virus vaccine strains delivered individually with a novel dissolving microneedle patch and the stability of this formulation during storage at 25 °C. Our data demonstrate that all strains retained their antigenic activity after incorporation in the dissolving patches as measured by single radial diffusion (SRID) assay and immune responses to vaccination in BALB/c mice. After a single immunization, all three antigens delivered with microneedle patches induced superior neutralizing antibody titers compared to intramuscular immunization. Cutaneous antigen delivery was especially beneficial for the less immunogenic B strain. Mice immunized with dissolving microneedle patches encapsulating influenza A/Brisbane/59/07 (H1N1) vaccine were fully protected against lethal challenge by homologous mouse-adapted influenza virus. All vaccine components retained activity during storage at room temperature for at least 3 months as measured in vitro by SRID assay and in vivo by mouse immunization studies. Our data demonstrate that dissolving microneedle patches are a promising advance for influenza cutaneous vaccination due to improved immune responses using less immunogenic influenza antigens and enhanced stability.

  9. Improved immunogenicity of individual influenza vaccine components delivered with a novel dissolving microneedle patch stable at room temperature

    Science.gov (United States)

    Vassilieva, Elena V.; Kalluri, Haripriya; McAllister, Devin; Taherbhai, Misha T.; Esser, E. Stein; Pewin, Winston P.; Pulit-Penaloza, Joanna A.; Prausnitz, Mark R.; Compans, Richard W.; Skountzou, Ioanna

    2015-01-01

    Prevention of seasonal influenza epidemics and pandemics relies on widespread vaccination coverage to induce protective immunity. In addition to a good antigenic match with the circulating viruses, the effectiveness of individual strains represented in the trivalent vaccines depends on their immunogenicity. In this study we evaluated the immunogenicity of H1N1, H3N2 and B seasonal influenza virus vaccine strains delivered individually with a novel dissolving microneedle patch and the stability of this formulation during storage at 25°C. Our data demonstrate that all strains retained their antigenic activity after incorporation in the dissolving patches as measured by SRID assay and immune responses to vaccination in BALB/c mice. After a single immunization all three antigens delivered with microneedle patches induced superior neutralizing antibody titers compared to intramuscular immunization. Cutaneous antigen delivery was especially beneficial for the less immunogenic B strain. Mice immunized with dissolving microneedle patches encapsulating influenza A/Brisbane/59/07 (H1N1) vaccine were fully protected against lethal challenge by homologous mouse-adapted influenza virus. All vaccine components retained activity during storage at room temperature for at least three months as measured in vitro by SRID assay and in vivo by mouse immunization studies. Our data demonstrate that dissolving microneedle patches are a promising advance for influenza cutaneous vaccination due to improved immune responses using less immunogenic influenza antigens and enhanced stability. PMID:25895053

  10. Studies on trivalent lanthanide complexes of bis-vanillin p-phenylenediamine

    International Nuclear Information System (INIS)

    Shahma, Abu; Ahmad, Naseer

    1983-01-01

    The coordination interaction of lanthanide(III) chlorides with bis-vanillin o-phenylenediamine was studied by Ansari and Ahmad (1977). It was thought fruitful to compare these with the complexes of trivalent lanthanide ions with bis-vanillin p-phenylenediamine. The newly synthesized complexes were subjected to elemental, thermogravimetric and differential thermal analyses and their melting points, magnetic susceptibilities, molar conductances determined and infrared and electronic spectra taken. (author)

  11. Factors Affecting the Adsorption of Trivalent Chromium Ions by Activated Carbon Prepared from Waste Rubber Tyres

    OpenAIRE

    Sylvia E. Benjamin; Muhammad Ashfaq Sajjid

    2017-01-01

    Economic gains are generally the outcome of industrialization and consequently urbanization. However, positive fiscal index generates a negative impact on natural environment sources heaving pollutant burden on soil, air and water. Industries throw tones of contaminated water into soil and water bodies without proper treatment and create a potential threat for both living and non-living species. Chromium in trivalent state (Cr3+) is added in water bodies and soil through waste water from tann...

  12. Geochemical Modeling of Trivalent Chromium Migration in Saline-Sodic Soil during Lasagna Process: Impact on Soil Physicochemical Properties

    Science.gov (United States)

    Bukhari, Alaadin; Al-Malack, Muhammad H.; Mu'azu, Nuhu D.; Essa, Mohammed H.

    2014-01-01

    Trivalent Cr is one of the heavy metals that are difficult to be removed from soil using electrokinetic study because of its geochemical properties. High buffering capacity soil is expected to reduce the mobility of the trivalent Cr and subsequently reduce the remedial efficiency thereby complicating the remediation process. In this study, geochemical modeling and migration of trivalent Cr in saline-sodic soil (high buffering capacity and alkaline) during integrated electrokinetics-adsorption remediation, called the Lasagna process, were investigated. The remedial efficiency of trivalent Cr in addition to the impacts of the Lasagna process on the physicochemical properties of the soil was studied. Box-Behnken design was used to study the interaction effects of voltage gradient, initial contaminant concentration, and polarity reversal rate on the soil pH, electroosmotic volume, soil electrical conductivity, current, and remedial efficiency of trivalent Cr in saline-sodic soil that was artificially spiked with Cr, Cu, Cd, Pb, Hg, phenol, and kerosene. Overall desirability of 0.715 was attained at the following optimal conditions: voltage gradient 0.36 V/cm; polarity reversal rate 17.63 hr; soil pH 10.0. Under these conditions, the expected trivalent Cr remedial efficiency is 64.75 %. PMID:25152905

  13. A trivalent Apx-fusion protein delivered by E. coli outer membrane vesicles induce protection against Actinobacillus pleuropneumoniae of serotype 1 and 7 challenge in a murine model.

    Science.gov (United States)

    Xu, Kui; Zhao, Qin; Wen, Xintian; Wu, Rui; Wen, Yiping; Huang, Xiaobo; Huang, Yong; Yan, Qigui; Han, Xinfeng; Ma, Xiaoping; Chang, Yung-Fu; Cao, Sanjie

    2018-01-01

    Actinobacillus pleuropneumoniae (APP) causes serious economic losses in the swine industry, and is the etiologic agent of porcine pleuropneumonia. In this study we have engineered a trivalent Apx fusion protein enclosed in outer membrane vesicles (Apxr-OMV) and studied its immunoprotective efficacy against APP serotypes 1 and 7 challenge in mice. The results showed that the IgG levels in the Apxr-OMVs immune group were significantly higher than those of the negative control (P < 0.05). Up-regulation of both Th1 (IFN-γ, IL-2) and Th2 (IL-4) cytokines were detected in splenocytes of Apxr-OMVs immune group. The survival rates 87.5% and 62.5% were observed against APP strain 1516 of serotype 7 and APP strain 2701 of serotype 1 in the groups of Apxr-OMVs immune group, respectively. Histopathological lesions of the pulmonary structure alveoli were found to be minimal in APX-OMV group challenged with APP serotypes 1 and 7. These results strongly indicated that engineered OMVs could effectively induce specific humoral or cellular immune responses. Moreover, Apxr-OMVs used as novel vaccine provides cross-protective immunity against different serotype 1 and 7 of APP infection in a mouse model. In contrast, the OMV-empty and PBS as negative controls or inactivated strain of APP-2701 and APP-1516 as positive controls for the animal study cannot provide protection or cross-protection.

  14. Swine Influenza/Variant Influenza Viruses

    Science.gov (United States)

    ... Humans Key Facts about Human Infections with Variant Viruses Interim Guidance for Clinicians on Human Infections Background, Risk Assessment & Reporting Reported Infections with Variant Influenza Viruses in the United States since 2005 Past Outbreaks ...

  15. Extraction characteristics of trivalent lanthanides and actinides in mixtures of dinonylnaphthalenesulfonic acid and carboxylic acids

    International Nuclear Information System (INIS)

    West, M.H.

    1983-03-01

    Dinonylnaphthalenesulfonic acid (HDNNS) has been shown to be an effective liquid cation exchanger for the extraction of metal ions. This extractant has proven to be successful in the extraction of trivalent lanthanides and actinides in the pH range of 2.0 to 3.0, although it shows little selectivity for individual ions because of its strong acid character. In an effort to improve the selectivity of HDNNS between trivalent lanthanides and actinides, carboxylic acids were added to the organic phase and the effects on the extraction characteristics of HDNNS were investigated. Three carboxylic acids - nonanoic, cyclohexanecarboxylic, and cyclohexanebutyric - were studied with the following metals: Am(III), Cm(III), Ce(III), Eu(III), and Tm(III). The distributions of the metal ions were studied holding the HDNNS concentration constant while varying the carboxylic acid concentrations over a range of 1.0 x 10 -5 M to 1.0 M. Results indicated that the greatest enhancement of the extraction occurred at a carboxylic acid concentration of 1.0 x 10 -2 M with negative effects occurring at 0.5 M and 1.0 M. The effects on the extraction of the trivalent lanthanides and actinides were interpreted in terms of the structural differences of the carboxylic acids, the effect of the carboxylic acids on the HDNNS extraction mechanism, and the ionic properties of the metals studied

  16. Linear free energy relationship applied to trivalent cations with lanthanum and actinium oxide and hydroxide structure

    International Nuclear Information System (INIS)

    Ragavan, Anpalaki J.

    2006-01-01

    Linear free energy relationships for trivalent cations with crystalline M 2 O 3 and, M(OH) 3 phases of lanthanides and actinides were developed from known thermodynamic properties of the aqueous trivalent cations, modifying the Sverjensky and Molling equation. The linear free energy relationship for trivalent cations is as ΔG f,MvX 0 =a MvX ΔG n,M 3+ 0 +b MvX +β MvX r M 3+ , where the coefficients a MvX , b MvX , and β MvX characterize a particular structural family of MvX, r M 3+ is the ionic radius of M 3+ cation, ΔG f,MvX 0 is the standard Gibbs free energy of formation of MvX and ΔG n,M 3+ 0 is the standard non-solvation free energy of the cation. The coefficients for the oxide family are: a MvX =0.2705, b MvX =-1984.75 (kJ/mol), and β MvX =197.24 (kJ/molnm). The coefficients for the hydroxide family are: a MvX =0.1587, b MvX =-1474.09 (kJ/mol), and β MvX =791.70 (kJ/molnm).

  17. Potential of Live Spirulina platensis on Biosorption of Hexavalent Chromium and Its Conversion to Trivalent Chromium.

    Science.gov (United States)

    Colla, Luciane Maria; Dal'Magro, Clinei; De Rossi, Andreia; Thomé, Antônio; Reinehr, Christian Oliveira; Bertolin, Telma Elita; Costa, Jorge Alberto Vieira

    2015-01-01

    Microalga biomass has been described worldwide according their capacity to realize biosorption of toxic metals. Chromium is one of the most toxic metals that could contaminate superficial and underground water. Considering the importance of Spirulina biomass in production of supplements for humans and for animal feed we assessed the biosorption of hexavalent chromium by living Spirulina platensis and its capacity to convert hexavalent chromium to trivalent chromium, less toxic, through its metabolism during growth. The active biomass was grown in Zarrouk medium diluted to 50% with distilled water, keeping the experiments under controlled conditions of aeration, temperature of 30°C and lighting of 1,800 lux. Hexavalent chromium was added using a potassium dichromate solution in fed-batch mode with the aim of evaluate the effect of several additions contaminant in the kinetic parameters of the culture. Cell growth was affected by the presence of chromium added at the beginning of cultures, and the best growth rates were obtained at lower metal concentrations in the medium. The biomass removed until 65.2% of hexavalent chromium added to the media, being 90.4% converted into trivalent chromium in the media and 9.6% retained in the biomass as trivalent chromium (0.931 mg.g(-1)).

  18. Transdermal influenza immunization with vaccine-coated microneedle arrays.

    Directory of Open Access Journals (Sweden)

    Dimitrios G Koutsonanos

    Full Text Available Influenza is a contagious disease caused by a pathogenic virus, with outbreaks all over the world and thousands of hospitalizations and deaths every year. Due to virus antigenic drift and short-lived immune responses, annual vaccination is required. However, vaccine coverage is incomplete, and improvement in immunization is needed. The objective of this study is to investigate a novel method for transdermal delivery using metal microneedle arrays (MN coated with inactivated influenza virus to determine whether this route is a simpler and safer approach than the conventional immunization, capable to induce robust immune responses and confer protection against lethal virus challenge.Inactivated A/Aichi/2/68 (H3N2 influenza virus was coated on metal microneedle arrays and applied to mice as a vaccine in the caudal dorsal skin area. Substantial antibody titers with hemagglutination inhibition activity were detected in sera collected two and four weeks after a single vaccine dose. Challenge studies in mice with 5 x LD(50 of mouse adapted Aichi virus demonstrated complete protection. Microneedle vaccination induced a broad spectrum of immune responses including CD4+ and CD8+ responses in the spleen and draining lymph node, a high frequency of antigen-secreting cells in the lung and induction of virus-specific memory B-cells. In addition, the use of MN showed a dose-sparing effect and a strong Th2 bias when compared to an intramuscular (IM reference immunization.The present results show that delivery of inactivated influenza virus through the skin using metal microneedle arrays induced strong humoral and cellular immune responses capable of conferring protection against virus challenge as efficiently as intramuscular immunization, which is the standard vaccination route. In view of the convenience of delivery and the potential for self-administration, vaccine-coated metal microneedles may provide a novel and highly effective immunization method.

  19. Human PIEZO1: removing inactivation.

    Science.gov (United States)

    Bae, Chilman; Gottlieb, Philip A; Sachs, Frederick

    2013-08-20

    PIEZO1 is an inactivating eukaryotic cation-selective mechanosensitive ion channel. Two sites have been located in the channel that when individually mutated lead to xerocytotic anemia by slowing inactivation. By introducing mutations at two sites, one associated with xerocytosis and the other artificial, we were able to remove inactivation. The double mutant (DhPIEZO1) has a substitution of arginine for methionine (M2225R) and lysine for arginine (R2456K). The loss of inactivation was accompanied by ∼30-mmHg shift of the activation curve to lower pressures and slower rates of deactivation. The slope sensitivity of gating was the same for wild-type and mutants, indicating that the dimensional changes between the closed and open state are unaffected by the mutations. The unitary channel conductance was unchanged by mutations, so these sites are not associated with pore. DhPIEZO1 was reversibly inhibited by the peptide GsMTx4 that acted as a gating modifier. The channel kinetics were solved using complex stimulus waveforms and the data fit to a three-state loop in detailed balance. The reaction had two pressure-dependent rates, closed to open and inactivated to closed. Pressure sensitivity of the opening rate with no sensitivity of the closing rate means that the energy barrier between them is located near the open state. Mutant cycle analysis of inactivation showed that the two sites interacted strongly, even though they are postulated to be on opposite sides of the membrane. Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  20. Pandemic influenza 1918 H1N1 and 1968 H3N2 DNA vaccines induce cross-reactive immunity in ferrets against infection with viruses drifted for decades

    DEFF Research Database (Denmark)

    Bragstad, Karoline; Martel, Cyril; Thomsen, Joakim S.

    2011-01-01

    Please cite this paper as: Bragstad et al. (2010) Pandemic influenza 1918 H1N1 and 1968 H3N2 DNA vaccines induce cross-reactive immunity in ferrets against infection with viruses drifted for decades. Influenza and Other Respiratory Viruses 5(1), 13-23. Background Alternative influenza vaccines...... and vaccine production forms are needed as the conventional protein vaccines do not induce broad cross-reactivity against drifted strains. Furthermore, fast vaccine production is especially important in a pandemic situation, and broader vaccine reactivity would diminish the need for frequent change...... in the vaccine formulations. Objective In this study, we compared the ability of pandemic influenza DNA vaccines to induce immunity against distantly related strains within a subtype with the immunity induced by conventional trivalent protein vaccines against homologous virus challenge. Methods Ferrets were...

  1. Influenza vaccines in immunosuppressed adults with cancer.

    Science.gov (United States)

    Bitterman, Roni; Eliakim-Raz, Noa; Vinograd, Inbal; Zalmanovici Trestioreanu, Anca; Leibovici, Leonard; Paul, Mical

    2018-02-01

    This is an update of the Cochrane review published in 2013, Issue 10.Immunosuppressed cancer patients are at increased risk of serious influenza-related complications. Guidelines, therefore, recommend influenza vaccination for these patients. However, data on vaccine effectiveness in this population are lacking, and the value of vaccination in this population remains unclear. To assess the effectiveness of influenza vaccine in immunosuppressed adults with malignancies. The primary review outcome is all-cause mortality, preferably at the end of the influenza season. Influenza-like illness (ILI, a clinical definition), confirmed influenza, pneumonia, any hospitalisations, influenza-related mortality and immunogenicity were defined as secondary outcomes. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and LILACS databases up to May 2017. We searched the following conference proceedings: ICAAC, ECCMID, IDSA (infectious disease conferences), ASH, ASBMT, EBMT (haematological), and ASCO (oncological) between the years 2006 to 2017. In addition, we scanned the references of all identified studies and pertinent reviews. We searched the websites of the manufacturers of influenza vaccine. Finally, we searched for ongoing or unpublished trials in clinical trial registry databases. Randomised controlled trials (RCTs), prospective and retrospective cohort studies and case-control studies were considered, comparing inactivated influenza vaccines versus placebo, no vaccination or a different vaccine, in adults (16 years and over) with cancer. We considered solid malignancies treated with chemotherapy, haematological cancer patients treated or not treated with chemotherapy, cancer patients post-autologous (up to six months after transplantation) or allogeneic (at any time) haematopoietic stem cell transplantation (HSCT). Two review authors independently assessed the risk of bias and extracted data from included studies adhering to Cochrane

  2. Influenza: prevention, prophylaxis and treatment

    African Journals Online (AJOL)

    Influenza A tends to cause moderate to severe illness in all age groups, and can infect humans and animals, including birds. Influenza B causes milder disease only in humans, primarily in children. Influenza C has rarely been reported to affect humans. The problem with the influenza virus is that it undergoes antigenic.

  3. Avian influenza virus

    Science.gov (United States)

    Avian influenza virus (AIV) is type A influenza that is adapted to avian host species. Although the virus can be isolated from numerous avian species, the natural host reservoir species are dabbling ducks, shorebirds and gulls. Domestic poultry species (poultry being defined as birds that are rais...

  4. Seasonal Influenza: An Overview

    Science.gov (United States)

    Li, Christina; Freedman, Marian

    2009-01-01

    Seasonal influenza is a major cause of morbidity and mortality in the United States. It also has major social and economic consequences in the form of high rates of absenteeism from school and work as well as significant treatment and hospitalization costs. In fact, annual influenza epidemics and the resulting deaths and lost days of productivity…

  5. Towards universal influenza vaccines?

    NARCIS (Netherlands)

    A.D.M.E. Osterhaus (Albert); R.A.M. Fouchier (Ron); G.F. Rimmelzwaan (Guus)

    2011-01-01

    textabstractVaccination is the most cost-effective way to reduce the considerable disease burden of seasonal influenza. Although seasonal influenza vaccines are effective, their performance in the elderly and immunocompromised individuals would benefit from improvement. Major problems related to the

  6. Combination Chemotherapy for Influenza

    Directory of Open Access Journals (Sweden)

    Robert G. Webster

    2010-07-01

    Full Text Available The emergence of pandemic H1N1 influenza viruses in April 2009 and the continuous evolution of highly pathogenic H5N1 influenza viruses underscore the urgency of novel approaches to chemotherapy for human influenza infection. Anti-influenza drugs are currently limited to the neuraminidase inhibitors (oseltamivir and zanamivir and to M2 ion channel blockers (amantadine and rimantadine, although resistance to the latter class develops rapidly. Potential targets for the development of new anti-influenza agents include the viral polymerase (and endonuclease, the hemagglutinin, and the non-structural protein NS1. The limitations of monotherapy and the emergence of drug-resistant variants make combination chemotherapy the logical therapeutic option. Here we review the experimental data on combination chemotherapy with currently available agents and the development of new agents and therapy targets.

  7. Conventional influenza vaccines influence the performance of a universal influenza vaccine in mice.

    Science.gov (United States)

    Rowell, Janelle; Lo, Chia-Yun; Price, Graeme E; Misplon, Julia A; Epstein, Suzanne L; Garcia, Mayra

    2018-02-08

    Universal influenza vaccines are designed to protect against diverse strains of influenza virus. Preclinical testing of new vaccine candidates is usually done in naïve animals, despite intended use in the human population with its varied immune history including responses to previous vaccinations. As an approach more relevant to human use, we tested a candidate universal influenza vaccine in mice with a history of conventional vaccination. Female BALB/c mice were given two intramuscular doses of inactivated influenza vaccine (IIV) or diphtheria and tetanus toxoids vaccine (DT), one month apart. Another group was given two intranasal doses of live attenuated influenza virus (LAIV). One month after the second dose, mice were given the universal influenza vaccine: recombinant adenoviruses expressing influenza A nucleoprotein (A/NP) and matrix 2 (M2) (A/NP + M2-rAd). Immune responses to universal vaccine antigens A/NP and M2 were assessed by ELISA and interferon-γ ELISPOT. Protection was tested by challenge with mouse-adapted A/FM/1/47 (H1N1) and monitoring for weight loss and survival. Universal vaccine performance was enhanced, inhibited or unaffected by particular prior vaccinations. Mice given Afluria IIV and LAIV had greater antibody and T-cell response to A/NP than mice without prior vaccination, providing examples of enhanced A/NP + M2-rAd performance. Though Fluvirin IIV partially inhibited, the universal vaccine still provided considerable protection unlike conventional vaccination. Fluzone IIV and DT had no effect on A/NP + M2-rAd performance. Thus our results demonstrate that universal vaccine candidate A/NP + M2-rAd was at least partially effective in mice with diverse prior histories. However, the degree of protection and nature of the immune responses may be affected by a history of conventional vaccination and suggests that performance in humans would be influenced by immune history. Published by Elsevier Ltd.

  8. Translating vaccine policy into action: a report from the Bill & Melinda Gates Foundation Consultation on the prevention of maternal and early infant influenza in resource-limited settings.

    Science.gov (United States)

    Ortiz, Justin R; Neuzil, Kathleen M; Ahonkhai, Vincent I; Gellin, Bruce G; Salisbury, David M; Read, Jennifer S; Adegbola, Richard A; Abramson, Jon S

    2012-11-26

    Immunization of pregnant women against influenza is a promising strategy to protect the mother, fetus, and young infant from influenza-related diseases. The burden of influenza during pregnancy, the vaccine immunogenicity during this period, and the robust influenza vaccine safety database underpin recommendations that all pregnant women receive the vaccine to decrease complications of influenza disease during their pregnancies. Recent data also support maternal immunization for the additional purpose of preventing disease in the infant during the first six months of life. In April 2012, the WHO Strategic Advisory Group of Experts (SAGE) on Immunization recommended revisions to the WHO position paper on influenza vaccines. For the first time, SAGE recommended pregnant women should be made the highest priority for inactivated seasonal influenza vaccination. However, the variable maternal influenza vaccination coverage in countries with pre-existing maternal influenza vaccine recommendations underscores the need to understand and to address the discrepancy between recommendations and implementation success. We present the outcome of a multi-stakeholder expert consultation on inactivated influenza vaccination in pregnancy. The creation and implementation of vaccine policies and regulations require substantial resources and capacity. As with all public health interventions, the existence of perceived and real risks of vaccination will necessitate effective and transparent risk communication. Potential risk allocation and sharing mechanisms should be addressed by governments, vaccine manufacturers, and other stakeholders. In resource-limited settings, vaccine-related issues concerning supply, formulation, regulation, evidence evaluation, distribution, cost-utility, and post-marketing safety surveillance need to be addressed. Lessons can be learned from the Maternal and Neonatal Tetanus Elimination Initiative as well as efforts to increase vaccine coverage among pregnant

  9. Inactivation of enveloped viruses by anthraquinones extracted from plants.

    Science.gov (United States)

    Sydiskis, R J; Owen, D G; Lohr, J L; Rosler, K H; Blomster, R N

    1991-01-01

    To determine the extent of antiviral activity present in a number of plant extracts, hot glycerin extracts were prepared from Rheum officinale, Aloe barbadensis, Rhamnus frangula, Rhamnus purshianus, and Cassia angustifolia and their virucidal effects were tested against herpes simplex virus type 1. All the plant extracts inactivated the virus. The active components in these plants were separated by thin-layer chromatography and identified as anthraquinones. A purified sample of aloe emodin was prepared from aloin, and its effects on the infectivity of herpes simplex virus type 1 and type 2, varicella-zoster virus, pseudorabies virus, influenza virus, adenovirus, and rhinovirus were tested by mixing virus with dilutions of aloe emodin for 15 min at 37 degrees C, immediately diluting the sample, and assaying the amount of infectious virus remaining in the sample. The results showed that aloe emodin inactivated all of the viruses tested except adenovirus and rhinovirus. Electron microscopic examination of anthraquinone-treated herpes simplex virus demonstrated that the envelopes were partially disrupted. These results show that anthraquinones extracted from a variety of plants are directly virucidal to enveloped viruses. PMID:1810179

  10. Immunologic evaluation of 10 different adjuvants for use in vaccines for chickens against highly pathogenic avian influenza virus

    Science.gov (United States)

    Avian influenza viruses (AIV) are a threat to poultry production worldwide. Vaccination is utilized as a component of control programs for both high pathogenicity (HP) and low pathogenicity (LP) AIV. Over 95% of all AIV vaccine used in poultry are inactivated, adjuvanted products. To identify the be...

  11. Factors affecting induction of peripheral IFN-gamma recall response to influenza A virus vaccination in pigs

    Science.gov (United States)

    While T cell contribution to IAV immunity is appreciated, data comparing methods to evaluate IFN-gamma production by IAV-specific T cells elicited following vaccination is limited. To understand the differential immunogenicity between live-attenuated influenza virus (LAIV) and whole-inactivated viru...

  12. Vaccine protection of poultry against H5 clade 2.3.4.4 highly pathogenic avian influenza

    Science.gov (United States)

    Following the 2014-2015 outbreaks of H5N2 and H5N8 (clade 2.3.4.4) highly pathogenic avian influenza (HPAI) in the U.S., studies were performed to identify vaccines with potential to be used as a control mechanism in the event of future outbreaks. We tested both inactivated and recombinant vaccine...

  13. Characterization of the sorption behavior of trivalent actinides on zirconium(IV) oxide

    Energy Technology Data Exchange (ETDEWEB)

    Eibl, Manuel; Huittinen, Nina [Helmholtz-Zentrum Dresden-Rossendorf e.V., Dresden (Germany). Surface Processes; Virtanen, S.; Merilaeinen, S.; Lehto, J. [Helsinki Univ. (Finland); Rabung, T. [Karlsruhe Institute of Technology (KIT), Karlsruhe (Germany). Inst. for Nuclear Waste Disposal

    2017-06-01

    The uptake of trivalent Eu and Cm on zirconium(IV) oxide was investigated in batch sorption and TRLFS studies, respectively. Sorption of Eu{sup 3+} was found to start at a pH-value of 4. Based on TRLFS results, sorption of Cm{sup 3+} was assigned to occur through innersphere complex formation at the zirconia surface. A deconvolution of the TRLFS emission spectra gave three different sorption species with strong red-shifts of the peak positions (600.3 nm, 604.3 nm and 608.2 nm) compared to similar systems.

  14. Origin of the fluorescence of trivalent europium inclusions in ZnS matrices

    International Nuclear Information System (INIS)

    Charreire, Yves; Loriers, Jean

    1977-01-01

    The red fluorescence of trivalent europium associated in zinc sulfide with another but optically inactive lanthanide ion (La, Gd) originates from rare earth oxysulfide inclusions, that are always formed during the preparation of the compounds. This interpretation results from the examination of the materials by X-ray diffraction, optical and electronic microscopy and from the study of their absorption, excitation and luminescence spectra. It allows one to understand some of the observed properties, which were left unexplained by the assumption that the Eu 3+ ions enter the ZnS crystal lattice [fr

  15. Methylated trivalent arsenicals are potent inhibitors of glucose stimulated insulin secretion by murine pancreatic islets

    Energy Technology Data Exchange (ETDEWEB)

    Douillet, Christelle [Department of Nutrition, Gillings School of Global Public Health, 2302 MHRC, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7461 (United States); Currier, Jenna [Curriculum in Toxicology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7461 (United States); Saunders, Jesse [Department of Nutrition, Gillings School of Global Public Health, 2302 MHRC, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7461 (United States); Bodnar, Wanda M. [Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7431 (United States); Matoušek, Tomáš [Institute of Analytical Chemistry of the ASCR, v.v.i., Veveří 97, 602 00 Brno (Czech Republic); Stýblo, Miroslav, E-mail: styblo@med.unc.edu [Department of Nutrition, Gillings School of Global Public Health, 2302 MHRC, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7461 (United States)

    2013-02-15

    Epidemiologic evidence has linked chronic exposure to inorganic arsenic (iAs) with an increased prevalence of diabetes mellitus. Laboratory studies have identified several mechanisms by which iAs can impair glucose homeostasis. We have previously shown that micromolar concentrations of arsenite (iAs{sup III}) or its methylated trivalent metabolites, methylarsonite (MAs{sup III}) and dimethylarsinite (DMAs{sup III}), inhibit the insulin-activated signal transduction pathway, resulting in insulin resistance in adipocytes. Our present study examined effects of the trivalent arsenicals on insulin secretion by intact pancreatic islets isolated from C57BL/6 mice. We found that 48-hour exposures to low subtoxic concentrations of iAs{sup III}, MAs{sup III} or DMAs{sup III} inhibited glucose-stimulated insulin secretion (GSIS), but not basal insulin secretion. MAs{sup III} and DMAs{sup III} were more potent than iAs{sup III} as GSIS inhibitors with estimated IC{sub 50} ≤ 0.1 μM. The exposures had little or no effects on insulin content of the islets or on insulin expression, suggesting that trivalent arsenicals interfere with mechanisms regulating packaging of the insulin transport vesicles or with translocation of these vesicles to the plasma membrane. Notably, the inhibition of GSIS by iAs{sup III}, MAs{sup III} or DMAs{sup III} could be reversed by a 24-hour incubation of the islets in arsenic-free medium. These results suggest that the insulin producing pancreatic β-cells are among the targets for iAs exposure and that the inhibition of GSIS by low concentrations of the methylated metabolites of iAs may be the key mechanism of iAs-induced diabetes. - Highlights: ► Trivalent arsenicals inhibit glucose stimulated insulin secretion by pancreatic islets. ► MAs{sup III} and DMAs{sup III} are more potent inhibitors than arsenite with IC{sub 50} ∼ 0.1 μM. ► The arsenicals have little or no effects on insulin expression in pancreatic islets. ► The inhibition of

  16. Synthesis and structural studies of some trivalent lanthanide complexes of isonicotinic acid hydrazide

    International Nuclear Information System (INIS)

    Rao, T.R.; Khan, I.A.; Aggarwal, R.C.

    1985-01-01

    Trivalent lanthanides have been found to form complexes with isonicotinic acid hydrazide (INH) of the type M(INH) 3 X 3 [X=Cl, SCN; M=La(III), Pr(III), Nd(III), Sm(III) and Gd(III)]. The complexes have been characterized by elemental analysis, molar conductance, magnetic susceptibility, infrared and electronic spectral studies. The nephelauxetic ratio (β), covalency (δ) and bonding parameter (b 1/1 ) have been calculated from the electronic spectra. Infrared spectral studies reveal that INH acts as a neutral bidentate chelating ligand in all the complexes and that thiocyanate is N-bonded. (author)

  17. Pandemic influenza: certain uncertainties.

    Science.gov (United States)

    Morens, David M; Taubenberger, Jeffery K

    2011-09-01

    For at least five centuries, major epidemics and pandemics of influenza have occurred unexpectedly and at irregular intervals. Despite the modern notion that pandemic influenza is a distinct phenomenon obeying such constant (if incompletely understood) rules such as dramatic genetic change, cyclicity, "wave" patterning, virus replacement, and predictable epidemic behavior, much evidence suggests the opposite. Although there is much that we know about pandemic influenza, there appears to be much more that we do not know. Pandemics arise as a result of various genetic mechanisms, have no predictable patterns of mortality among different age groups, and vary greatly in how and when they arise and recur. Some are followed by new pandemics, whereas others fade gradually or abruptly into long-term endemicity. Human influenza pandemics have been caused by viruses that evolved singly or in co-circulation with other pandemic virus descendants and often have involved significant transmission between, or establishment of, viral reservoirs within other animal hosts. In recent decades, pandemic influenza has continued to produce numerous unanticipated events that expose fundamental gaps in scientific knowledge. Influenza pandemics appear to be not a single phenomenon but a heterogeneous collection of viral evolutionary events whose similarities are overshadowed by important differences, the determinants of which remain poorly understood. These uncertainties make it difficult to predict influenza pandemics and, therefore, to adequately plan to prevent them. Published 2011. This article is a US Government work and is in the public domain in the USA.

  18. Pandemic influenza: certain uncertainties

    Science.gov (United States)

    Morens, David M.; Taubenberger, Jeffery K.

    2011-01-01

    SUMMARY For at least five centuries, major epidemics and pandemics of influenza have occurred unexpectedly and at irregular intervals. Despite the modern notion that pandemic influenza is a distinct phenomenon obeying such constant (if incompletely understood) rules such as dramatic genetic change, cyclicity, “wave” patterning, virus replacement, and predictable epidemic behavior, much evidence suggests the opposite. Although there is much that we know about pandemic influenza, there appears to be much more that we do not know. Pandemics arise as a result of various genetic mechanisms, have no predictable patterns of mortality among different age groups, and vary greatly in how and when they arise and recur. Some are followed by new pandemics, whereas others fade gradually or abruptly into long-term endemicity. Human influenza pandemics have been caused by viruses that evolved singly or in co-circulation with other pandemic virus descendants and often have involved significant transmission between, or establishment of, viral reservoirs within other animal hosts. In recent decades, pandemic influenza has continued to produce numerous unanticipated events that expose fundamental gaps in scientific knowledge. Influenza pandemics appear to be not a single phenomenon but a heterogeneous collection of viral evolutionary events whose similarities are overshadowed by important differences, the determinants of which remain poorly understood. These uncertainties make it difficult to predict influenza pandemics and, therefore, to adequately plan to prevent them. PMID:21706672

  19. Cold adaptation improves the growth of seasonal influenza B vaccine viruses.

    Science.gov (United States)

    Kim, Hyunsuh; Schoofs, Peter; Anderson, David A; Tannock, Gregory A; Rockman, Steven P

    2014-05-01

    Gene reassortment has proved useful in improving yields of influenza A antigens of egg-based inactivated vaccines, but similar approaches have been difficult with influenza B antigens. Current regulations for influenza vaccine seed viruses limit the number of egg passages and as a result resultant yields from influenza B vaccine seed viruses are frequently inconsistent. Therefore, reliable approaches to enhance yields of influenza B vaccine seed viruses are required for efficient vaccine manufacture. In the present study three stable cold-adapted (ca) mutants, caF, caM and caB derived from seasonal epidemic strains, B/Florida/4/2006, B/Malaysia/2506/2004 and B/Brisbane/60/2008 were prepared, which produced high hemagglutinin antigen yields and also increased viral yields of reassortants possessing the desired 6:2 gene constellation. The results demonstrate that consistent improvements in yields of influenza B viruses can be obtained by cold adaptation following extended passage. Taken together, the three ca viruses were shown to have potential as donor viruses for the preparation of high-yielding influenza B vaccine viruses by reassortment. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Advancing new vaccines against pandemic influenza in low-resource countries.

    Science.gov (United States)

    Berlanda Scorza, Francesco

    2017-09-25

    With the support of the Biomedical Advanced Research and Development Authority (BARDA), PATH is working with governments and vaccine manufacturers to strengthen their influenza vaccine manufacturing capacity and improve their ability to respond to emerging pandemic influenza viruses. Vaccines directed against influenza A/H5N1 and A/H7N9 strains are a particular focus, given the potential for these viruses to acquire properties that may lead to a pandemic. This paper will review influenza vaccine development from a developing country perspective and PATH's support of this effort. Several vaccines are currently in preclinical and clinical development at our partners for seasonal and pandemic influenza in Vietnam (IVAC and VABIOTECH), Serbia (Torlak), China (BCHT), Brazil (Butantan), and India (SII). Products in development include split, whole-virus inactivated and live attenuated influenza vaccines (LAIVs). Additionally, while most manufacturers propagate the virus in eggs, PATH is supporting the development of cell-based processes that could substantially increase global manufacturing capacity and flexibility. We review recent data from clinical trials of pandemic influenza vaccines manufactured in developing countries. An important discussion is on the role of whole virion vaccines for H5N1, given the poor immunogenicity of split vaccines and the complexity involved in developing potent adjuvants. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Effect of 25-Hydroxyvitamin D Status on Serological Response to Influenza Vaccine in Prostate Cancer Patients

    Science.gov (United States)

    Chadha, Manpreet K.; Fakih, Marwan; Muindi, Josephia; Tian, Lili; Mashtare, Terry; Johnson, Candace S.; Trump, Donald

    2015-01-01

    BACKGROUND Epidemiologic data suggest that there is an association between vitamin D deficiency and influenza infection. We conducted a prospective influenza vaccination study to determine the influence of vitamin D status on serological response to influenza vaccine in prostate cancer (CaP) patients. METHODS During the 2006–2007 influenza season, CaP patients treated at Roswell Park Cancer Institute were offered vaccination with the trivalent influenza vaccine (Fluzone®, 2006–2007) and sera collected for hemagglutination inhibition (HI) assay titers before and 3 months after vaccination. Response to vaccination was defined as ≥1:40 titer ratio or a fourfold increase in titer at 3 months, against any of the three strains. Serum 25-hydroxyvitamin D (25-D3) levels were measured using DiaSorin 125I radioimmunoassay kits. RESULTS Thirty-five patients with CaP participated in the study. Median baseline 25-D3 level was 44.88 ng/ml (range: 9.16–71.98 ng/ml) Serological response against any of the three strains was noted in 80%. There was a significant effect of baseline 25-D3 level when tested as a continuous variable in relation to serological response (P = 0.0446). All patients in the upper quartile of 25-D3 level responded by mounting a serological response (P = 0.0344). None of the other baseline variables (age, race, chemotherapy status, or white cell count) had an effect on serological response. CONCLUSIONS In this study in CaP patients, a replete vitamin D status was associated with more frequent serological response to influenza vaccine. PMID:20812224

  2. Public health impact and economic benefits of quadrivalent influenza vaccine in Latin America.

    Science.gov (United States)

    Jamotte, Aurélien; Clay, Emilie; Macabeo, Bérengère; Caicedo, Andrès; Lopez, Juan Guillermo; Bricks, Lucia; Romero Prada, Martín; Marrugo, Rubén; Alfonso, Pamela; Moreno Arévalo, Brechla; Franco, Danilo; Garcia Diaz, Lourdes; Isaza de Molto, Yadira

    2017-04-03

    Annual trivalent influenza vaccines (TIV) containing 2 A strains and one B lineage have been recommended for the prevention of influenza in most of Latin American countries. However, the circulation of 2 B lineages (Victoria and Yamagata) and difficulties in predicting the predominating lineage have led to the development of quadrivalent influenza vaccines (QIV), including both B lineages. Thus, the objective was to estimate the public health impact and influenza-related costs if QIV would have been used instead of TIV in 3 Latin American countries. We used a static model over the seasons 2010-2014 in Brazil, 2007-2014 in Colombia and 2006-2014 in Panama, focusing on population groups targeted by local vaccination recommendations: young children, adults with risk factors and the elderly. In Brazil, between 2010 and 2014, using QIV instead of TIV would have avoided US$ 6,200 per 100,000 person-years in societal costs, based on 168 influenza cases, 89 consultations, 3.2 hospitalizations and 0.38 deaths per 100,000 person-years. In Colombia and Panama, these would have ranged from US$ 1,000 to 12,700 (based on 34 cases, 13-25 consultations, 0.6-8.9 hospitalizations and 0.04-1.74 deaths) and from US$ 3,000 to 33,700 (based on 113 cases, 55-82 consultations, 0.5-27.8 hospitalizations and 0.08-6.87 deaths) per 100,000 person-years, respectively. Overall, the broader protection offered by QIV would have reduced the influenza humanistic and economic burden in the 3 countries. Despite the lack of local data leading to several extrapolations, this study is the first to give quantitative estimates of the potential benefits of QIV in Latin America.

  3. Public health impact and economic benefits of quadrivalent influenza vaccine in Latin America

    Science.gov (United States)

    Jamotte, Aurélien; Clay, Emilie; Macabeo, Bérengère; Caicedo, Andrès; Lopez, Juan Guillermo; Bricks, Lucia; Romero Prada, Martín; Marrugo, Rubén; Alfonso, Pamela; Moreno Arévalo, Brechla; Franco, Danilo; Garcia Diaz, Lourdes; Isaza de Molto, Yadira

    2017-01-01

    ABSTRACT Annual trivalent influenza vaccines (TIV) containing 2 A strains and one B lineage have been recommended for the prevention of influenza in most of Latin American countries. However, the circulation of 2 B lineages (Victoria and Yamagata) and difficulties in predicting the predominating lineage have led to the development of quadrivalent influenza vaccines (QIV), including both B lineages. Thus, the objective was to estimate the public health impact and influenza-related costs if QIV would have been used instead of TIV in 3 Latin American countries. We used a static model over the seasons 2010–2014 in Brazil, 2007–2014 in Colombia and 2006–2014 in Panama, focusing on population groups targeted by local vaccination recommendations: young children, adults with risk factors and the elderly. In Brazil, between 2010 and 2014, using QIV instead of TIV would have avoided US$ 6,200 per 100,000 person-years in societal costs, based on 168 influenza cases, 89 consultations, 3.2 hospitalizations and 0.38 deaths per 100,000 person-years. In Colombia and Panama, these would have ranged from US$ 1,000 to 12,700 (based on 34 cases, 13–25 consultations, 0.6–8.9 hospitalizations and 0.04–1.74 deaths) and from US$ 3,000 to 33,700 (based on 113 cases, 55–82 consultations, 0.5–27.8 hospitalizations and 0.08–6.87 deaths) per 100,000 person-years, respectively. Overall, the broader protection offered by QIV would have reduced the influenza humanistic and economic burden in the 3 countries. Despite the lack of local data leading to several extrapolations, this study is the first to give quantitative estimates of the potential benefits of QIV in Latin America. PMID:28118092

  4. Development and introduction of inactivated poliovirus vaccines derived from Sabin strains in Japan.

    Science.gov (United States)

    Shimizu, Hiroyuki

    2016-04-07

    During the endgame of global polio eradication, the universal introduction of inactivated poliovirus vaccines is urgently required to reduce the risk of vaccine-associated paralytic poliomyelitis and polio outbreaks due to wild and vaccine-derived polioviruses. In particular, the development of inactivated poliovirus vaccines (IPVs) derived from the attenuated Sabin strains is considered to be a highly favorable option for the production of novel IPV that reduce the risk of facility-acquired transmission of poliovirus to the communities. In Japan, Sabin-derived IPVs (sIPVs) have been developed and introduced for routine immunization in November 2012. They are the first licensed sIPVs in the world. Consequently, trivalent oral poliovirus vaccine was used for polio control in Japan for more than half a century but has now been removed from the list of vaccines licensed for routine immunization. This paper reviews the development, introduction, characterization, and global status of IPV derived from attenuated Sabin strains. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. I-MOVE multi-centre case control study 2010-11: overall and stratified estimates of influenza vaccine effectiveness in Europe.

    Science.gov (United States)

    Kissling, Esther; Valenciano, Marta; Cohen, Jean Marie; Oroszi, Beatrix; Barret, Anne-Sophie; Rizzo, Caterina; Stefanoff, Pawel; Nunes, Baltazar; Pitigoi, Daniela; Larrauri, Amparo; Daviaud, Isabelle; Horvath, Judit Krisztina; O'Donnell, Joan; Seyler, Thomas; Paradowska-Stankiewicz, Iwona Anna; Pechirra, Pedro; Ivanciuc, Alina Elena; Jiménez-Jorge, Silvia; Savulescu, Camelia; Ciancio, Bruno Christian; Moren, Alain

    2011-01-01

    In the third season of I-MOVE (Influenza Monitoring Vaccine Effectiveness in Europe), we undertook a multicentre case-control study based on sentinel practitioner surveillance networks in eight European Union (EU) member states to estimate 2010/11 influenza vaccine effectiveness (VE) against medically-attended influenza-like illness (ILI) laboratory-confirmed as influenza. Using systematic sampling, practitioners swabbed ILI/ARI patients within seven days of symptom onset. We compared influenza-positive to influenza laboratory-negative patients among those meeting the EU ILI case definition. A valid vaccination corresponded to > 14 days between receiving a dose of vaccine and symptom onset. We used multiple imputation with chained equations to estimate missing values. Using logistic regression with study as fixed effect we calculated influenza VE adjusting for potential confounders. We estimated influenza VE overall, by influenza type, age group and among the target group for vaccination. We included 2019 cases and 2391 controls in the analysis. Adjusted VE was 52% (95% CI 30-67) overall (N = 4410), 55% (95% CI 29-72) against A(H1N1) and 50% (95% CI 14-71) against influenza B. Adjusted VE against all influenza subtypes was 66% (95% CI 15-86), 41% (95% CI -3-66) and 60% (95% CI 17-81) among those aged 0-14, 15-59 and ≥60 respectively. Among target groups for vaccination (N = 1004), VE was 56% (95% CI 34-71) overall, 59% (95% CI 32-75) against A(H1N1) and 63% (95% CI 31-81) against influenza B. Results suggest moderate protection from 2010-11 trivalent influenza vaccines against medically-attended ILI laboratory-confirmed as influenza across Europe. Adjusted and stratified influenza VE estimates are possible with the large sample size of this multi-centre case-control. I-MOVE shows how a network can provide precise summary VE measures across Europe.

  6. I-MOVE multi-centre case control study 2010-11: overall and stratified estimates of influenza vaccine effectiveness in Europe.

    Directory of Open Access Journals (Sweden)

    Esther Kissling

    Full Text Available BACKGROUND: In the third season of I-MOVE (Influenza Monitoring Vaccine Effectiveness in Europe, we undertook a multicentre case-control study based on sentinel practitioner surveillance networks in eight European Union (EU member states to estimate 2010/11 influenza vaccine effectiveness (VE against medically-attended influenza-like illness (ILI laboratory-confirmed as influenza. METHODS: Using systematic sampling, practitioners swabbed ILI/ARI patients within seven days of symptom onset. We compared influenza-positive to influenza laboratory-negative patients among those meeting the EU ILI case definition. A valid vaccination corresponded to > 14 days between receiving a dose of vaccine and symptom onset. We used multiple imputation with chained equations to estimate missing values. Using logistic regression with study as fixed effect we calculated influenza VE adjusting for potential confounders. We estimated influenza VE overall, by influenza type, age group and among the target group for vaccination. RESULTS: We included 2019 cases and 2391 controls in the analysis. Adjusted VE was 52% (95% CI 30-67 overall (N = 4410, 55% (95% CI 29-72 against A(H1N1 and 50% (95% CI 14-71 against influenza B. Adjusted VE against all influenza subtypes was 66% (95% CI 15-86, 41% (95% CI -3-66 and 60% (95% CI 17-81 among those aged 0-14, 15-59 and ≥60 respectively. Among target groups for vaccination (N = 1004, VE was 56% (95% CI 34-71 overall, 59% (95% CI 32-75 against A(H1N1 and 63% (95% CI 31-81 against influenza B. CONCLUSIONS: Results suggest moderate protection from 2010-11 trivalent influenza vaccines against medically-attended ILI laboratory-confirmed as influenza across Europe. Adjusted and stratified influenza VE estimates are possible with the large sample size of this multi-centre case-control. I-MOVE shows how a network can provide precise summary VE measures across Europe.

  7. Quadrivalent influenza vaccine: a new opportunity to reduce the influenza burden

    OpenAIRE

    Tisa, V.; Barberis, I.; Faccio, V.; Paganino, C.; Trucchi, C.; Martini, M.; Ansaldi, F.

    2016-01-01

    Summary Influenza illness is caused by influenza A and influenza B strains. Although influenza A viruses are perceived to carry greater risk because they account for the majority of influenza cases in most seasons and have been responsible for influenza pandemics, influenza B viruses also impose a substantial public health burden, particularly among children and at-risk subjects. Furthermore, since the 2001-2002 influenza season, both influenza B lineages, B/Victoria-like viruses and B/Yamaga...

  8. A trivalent subunit antigen glycoprotein vaccine as immunotherapy for genital herpes in the guinea pig genital infection model.

    Science.gov (United States)

    Awasthi, Sita; Hook, Lauren M; Shaw, Carolyn E; Friedman, Harvey M

    2017-12-02

    An estimated 417 million people worldwide ages 15 to 49 are infected with herpes simplex virus type 2 (HSV-2), the most common cause of genital ulcer disease. Some individuals experience frequent recurrences of genital lesions, while others only have subclinical infection, yet all risk transmitting infection to their intimate partners. A vaccine was developed that prevents shingles, which is a recurrent infection caused by varicella-zoster virus (VZV), a closely related member of the Herpesviridae family. The success of the VZV vaccine has stimulated renewed interest in a therapeutic vaccine for genital herpes. We have been evaluating a trivalent subunit antigen vaccine for prevention of genital herpes. Here, we assess the trivalent vaccine as immunotherapy in guinea pigs that were previously infected intravaginally with HSV-2. The trivalent vaccine contains HSV-2 glycoproteins C, D, and E (gC2, gD2, gE2) subunit antigens administered with CpG and alum as adjuvants. We previously demonstrated that antibodies to gD2 neutralize the virus while antibodies to gC2 and gE2 block their immune evasion activities, including evading complement attack and inhibiting activities mediated by the IgG Fc domain, respectively. Here, we demonstrate that the trivalent vaccine significantly boosts ELISA titers and neutralizing antibody titers. The trivalent vaccine reduces the frequency of recurrent genital lesions and vaginal shedding of HSV-2 DNA by approximately 50% and almost totally eliminates vaginal shedding of replication-competent virus, suggesting that the trivalent vaccine is a worthy candidate for immunotherapy of genital herpes.

  9. Inactivation of allergens and toxins.

    Science.gov (United States)

    Morandini, Piero

    2010-11-30

    Plants are replete with thousands of proteins and small molecules, many of which are species-specific, poisonous or dangerous. Over time humans have learned to avoid dangerous plants or inactivate many toxic components in food plants, but there is still room for ameliorating food crops (and plants in general) in terms of their allergens and toxins content, especially in their edible parts. Inactivation at the genetic rather than physical or chemical level has many advantages and classical genetic approaches have resulted in significant reduction of toxin content. The capacity, offered by genetic engineering, of turning off (inactivating) specific genes has opened up the possibility of altering the plant content in a far more precise manner than previously available. Different levels of intervention (genes coding for toxins/allergens or for enzymes, transporters or regulators involved in their metabolism) are possible and there are several tools for inactivating genes, both direct (using chemical and physical mutagens, insertion of transposons and other genetic elements) and indirect (antisense RNA, RNA interference, microRNA, eventually leading to gene silencing). Each level/strategy has specific advantages and disadvantages (speed, costs, selectivity, stability, reversibility, frequency of desired genotype and regulatory regime). Paradigmatic examples from classical and transgenic approaches are discussed to emphasize the need to revise the present regulatory process. Reducing the content of natural toxins is a trade-off process: the lesser the content of natural toxins, the higher the susceptibility of a plant to pests and therefore the stronger the need to protect plants. As a consequence, more specific pesticides like Bt are needed to substitute for general pesticides. Copyright © 2010 Elsevier B.V. All rights reserved.

  10. Analysis of trivalent cation complexation to functionalized mesoporous silica using solid-state NMR spectroscopy.

    Science.gov (United States)

    Shusterman, Jennifer; Mason, Harris; Bruchet, Anthony; Zavarin, Mavrik; Kersting, Annie B; Nitsche, Heino

    2014-11-28

    Functionalized mesoporous silica has applications in separations science, catalysis, and sensors. In this work, we studied the fundamental interactions of trivalent cations with functionalized mesoporous silica. We contacted trivalent cations of varying ionic radii with N-[5-(trimethoxysilyl)-2-aza-1-oxopentyl]caprolactam functionalized mesoporous silica with the aim of probing the binding mechanism of the metal to the surface of the solid. We studied the functionalized silica using solid-state nuclear magnetic resonance (NMR) spectroscopy before and after contact with the metals of interest. We collected NMR spectra of the various metals, as well as of (29)Si and (13)C to probe the silica substrate and the ligand properties, respectively. The NMR spectra indicate that the metals bind to the functionalized silica via two mechanisms. Aluminum sorbed to both the silica and the ligand, but with different coordination for each. Scandium also sorbed to both the silica and the ligand, and unlike the aluminum, had the same coordination number. Additionally, the functionalized silica was susceptible to acid hydrolysis and two primary mechanisms of degradation were observed: detachment from the silica surface and opening of the seven-membered ring in the ligand. Opening of the seven-membered ring may be beneficial in that it decreases steric hindrance of the molecule for binding.

  11. Identification of Pyridinoline Trivalent Collagen Cross-Links by Raman Microspectroscopy.

    Science.gov (United States)

    Gamsjaeger, Sonja; Robins, Simon P; Tatakis, Dimitris N; Klaushofer, Klaus; Paschalis, Eleftherios P

    2017-06-01

    Intermolecular cross-linking of bone collagen is intimately related to the way collagen molecules are arranged in a fibril, imparts certain mechanical properties to the fibril, and may be involved in the initiation of mineralization. Raman microspectroscopy allows the analysis of minimally processed bone blocks and provides simultaneous information on both the mineral and organic matrix (mainly type I collagen) components, with a spatial resolution of ~1 μm. The aim of the present study was to validate Raman spectroscopic parameters describing one of the major mineralizing type I trivalent cross-links, namely pyridinoline (PYD). To achieve this, a series of collagen cross-linked peptides with known PYD content (as determined by HPLC analysis), human bone, porcine skin, predentin and dentin animal model tissues were analyzed by Raman microspectroscopy. The results of the present study confirm that it is feasible to monitor PYD trivalent collagen cross-links by Raman spectroscopic analysis in mineralized tissues, exclusively through a Raman band ~1660 wavenumbers. This allows determination of the relative PYD content in undecalcified bone tissues with a spatial resolution of ~1 μm, thus enabling correlations with histologic and histomorphometric parameters.

  12. New trivalent ion conducting solid electrolyte with the NASICON type structure

    Energy Technology Data Exchange (ETDEWEB)

    Hasegawa, Y.; Tamura, S.; Imanaka, N.; Adachi, G

    2004-10-06

    New trivalent ion conducting solid electrolytes with NASICON type structure, [(Ce{sub 1-x}La{sub x}){sub 0.1}Zr{sub 0.9}]{sub 40/39}Nb(PO{sub 4}){sub 3}, were successfully developed and their ion conducting behaviors were investigated. Among the [(Ce{sub 1-x}La{sub x}){sub 0.1}Zr{sub 0.9}]{sub 40/39}Nb(PO{sub 4}){sub 3} series prepared, the highest ion conductivity was obtained for [(Ce{sub 1-x}La{sub x}){sub 0.1}Zr{sub 0.9}]{sub 40/39}Nb(PO{sub 4}){sub 3} (x=0.8). The trivalent ion conductivity was approximately four times higher than that of cerium (Ce{sup 3+}) ion conducting (Ce{sub 0.1}Zr{sub 0.9}){sub 40/39}Nb(PO{sub 4}){sub 3}, and the values exceeded the region of the representative divalent oxide anion conductors such as yttria stabilized zirconia (YSZ) and calcia stabilized zirconia (CSZ) at temperatures below 500 deg. C.

  13. Cu L 3 x-ray absorption of formally trivalent Cu compounds

    Science.gov (United States)

    Bianconi, A.; Budnick, J.; Demazeau, G.; Flank, A. M.; Fontaine, A.; Lagarde, P.; Jegoudez, J.; Revcolevski, A.; Marcelli, A.; Verdaguer, M.

    1988-06-01

    The Cu L 3 X-ray Absorption Spectra (XAS) of formally trivalent Cu compounds NaCuO 2, La 2Li 0.5Cu 0.5O 4, and KCu(III)(biuret) 2 have been measured. The spectra of trivalent systems exhibit two white lines. The low energy white line is found to be at about the same energy, between 930.9 eV and 931.2 eV on the contrary the high energy white line in the range b