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Sample records for inactivated virus vaccines

  1. 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...

  2. 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.

  3. 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

  4. Field trials of an inactivated virus vaccine against porcine parvovirus.

    Science.gov (United States)

    Castro, J M; del Pozo, M; Simarro, I

    1992-07-01

    Serological response and reproductive performance were estimated in field trials of an inactivated virus vaccine against porcine parvovirus. Experiments were carried out in 10 selected pig breeding herds. A total of 277 seronegative gilts were used. Two hundred and twenty animals were vaccinated twice before mating, fourteen days apart and revaccinated after farrowing. Blood samples were obtained from both vaccinated and non-vaccinated (57 animal) control gilts, one week after the 2nd dose of vaccination, at farrowing time and one week after revaccination. Although there were considerable variations among the herds, the number of returns to oestrus in all herds was higher in vaccinated gilts (11.81%) than in the controls (10.52%). This difference, however, was not statistically significant. The reproductive performance results revealed the absence of an increase in the total born, as pooled values, in vaccinated gilts compared to controls. However, when these results are interpreted in relation to serological data, many control gilts were already seropositive before mating, or remained seronegative at farrowing. According to our results, the duration of immunity with this vaccine is apparently short, as there is a clear decrease in the titres between the 1st and the 2nd sampling times (2.35 +/- 0.14 and 1.97 +/- 0.08, respectively).

  5. 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...

  6. Vaccination of harbour seals (Phoca vitulina) against phocid distemper with two different inactivated canine distemper virus (CDV) vaccines.

    NARCIS (Netherlands)

    I.K.G. Visser (Ilona); M.W.G. van de Bildt (Marco); H.N. Brugge; P.J.H. Reijnders; E.J. Vedder (Lies); J. Kuiper; P. de Vries (Petra); J. Groen (Jan); H.C. Walvoort; F.G.C.M. Uytdehaag (Fons); A.D.M.E. Osterhaus (Albert)

    1989-01-01

    textabstractTwo inactivated canine distemper virus (CDV) vaccines--an adjuvanted whole inactivated virus and a subunit ISCOM preparation--were tested for their ability to induce protective immunity in harbour seals (Phoca vitulina) against phocid distemper, a disease that recently killed greater

  7. The assessment of efficacy of porcine reproductive respiratory syndrome virus inactivated vaccine based on the viral quantity and inactivation methods

    Directory of Open Access Journals (Sweden)

    Lee Byeongchun

    2011-06-01

    Full Text Available Abstract Background There have been many efforts to develop efficient vaccines for the control of porcine reproductive and respiratory syndrome virus (PRRSV. Although inactivated PRRSV vaccines are preferred for their safety, they are weak at inducing humoral immune responses and controlling field PRRSV infection, especially when heterologous viruses are involved. Results In all groups, the sample to positive (S/P ratio of IDEXX ELISA and the virus neutralization (VN titer remained negative until challenge. While viremia did not reduce in the vaccinated groups, the IDEXX-ELISA-specific immunoglobulin G increased more rapidly and to significantly greater levels 7 days after the challenge in all the vaccinated groups compared to the non-vaccinated groups (p 6 PFU/mL PRRSV vaccine-inoculated and binary ethylenimine (BEI-inactivated groups 22 days after challenge (p Conclusions The inactivated vaccine failed to show the humoral immunity, but it showed different immune response after the challenge compared to mock group. Although the 106 PFU/mL-vaccinated and BEI-inactivated groups showed significantly greater VN titers 22 days after challenge, all the groups were already negative for viremia.

  8. 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.

  9. 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

  10. Humoral response to 2 inactivated bluetongue virus serotype-8 vaccines in South American camelids.

    Science.gov (United States)

    Zanolari, P; Bruckner, L; Fricker, R; Kaufmann, C; Mudry, M; Griot, C; Meylan, M

    2010-01-01

    Bluetongue virus serotype 8 (BTV-8) has caused disease in domestic ruminants in several countries of northern Europe since 2006. In 2008 a mass-vaccination program was launched in most affected countries using whole virus inactivated vaccines. To evaluate 2 inactivated vaccines (Bovilis BTV 8; BTVPUR AlSap8) for immunogenicity and safety against BTV-8 in South American camelids (SAC) in a field trial. Forty-two SAC (25 Alpacas, 17 Llamas) aged between 1 and 16 years. The animals were vaccinated twice at intervals of 21 days. They were observed clinically for adverse local, systemic, or both reactions throughout the trial. Blood samples collected on days 0, 14, 21, 43, and 156 after vaccination were tested for the presence of BTV-8 virus by real time-polymerase chain reaction and of specific antibodies by competitive ELISA and a serum neutralization test. All vaccinated animals developed antibodies to BTV-8 after the 2nd administration of the vaccine. No adverse effects were observed except for moderate local swellings at the injection site, which disappeared within 21 days. Slightly increased body temperatures were only observed in the first 2 days after vaccination. The BTV was not detected in any of the samples analyzed. The administration of the 2 inactivated commercial vaccines was safe and induced seroconversion against BTV-8 in all vaccinated animals. The results of this study suggest that 2 doses injected 3 weeks apart is a suitable vaccination regimen for SAC.

  11. 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),...

  12. 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...

  13. Preclinical Development of Inactivated Rabies Virus-Based Polyvalent Vaccine Against Rabies and Filoviruses.

    Science.gov (United States)

    Willet, Mallory; Kurup, Drishya; Papaneri, Amy; Wirblich, Christoph; Hooper, Jay W; Kwilas, Steve A; Keshwara, Rohan; Hudacek, Andrew; Beilfuss, Stefanie; Rudolph, Grit; Pommerening, Elke; Vos, Adriaan; Neubert, Andreas; Jahrling, Peter; Blaney, Joseph E; Johnson, Reed F; Schnell, Matthias J

    2015-10-01

    We previously described the generation of a novel Ebola virus (EBOV) vaccine based on inactivated rabies virus (RABV) containing EBOV glycoprotein (GP) incorporated in the RABV virion. Our results demonstrated safety, immunogenicity, and protective efficacy in mice and nonhuman primates (NHPs). Protection against viral challenge depended largely on the quality of the humoral immune response against EBOV GP.Here we present the extension and improvement of this vaccine by increasing the amount of GP incorporation into virions via GP codon-optimization as well as the addition of Sudan virus (SUDV) and Marburg virus (MARV) GP containing virions. Immunogenicity studies in mice indicate similar immune responses for both SUDV GP and MARV GP compared to EBOV GP. Immunizing mice with multiple antigens resulted in immune responses similar to immunization with a single antigen. Moreover, immunization of NHP with the new inactivated RABV EBOV vaccine resulted in high titer neutralizing antibody levels and 100% protection against lethal EBOV challenge when applied with adjuvant.Our results indicate that an inactivated polyvalent vaccine against RABV filoviruses is achievable. Finally, the novel vaccines are produced on approved VERO cells and a clinical grade RABV/EBOV vaccine for human trials has been produced. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  14. Rabies virus pathogenesis in relationship to intervention with inactivated and attenuated rabies vaccines.

    Science.gov (United States)

    Franka, Richard; Wu, Xianfu; Jackson, Felix R; Velasco-Villa, Andres; Palmer, Dustyn P; Henderson, Heather; Hayat, Wajid; Green, Douglas B; Blanton, Jesse D; Greenberg, Lauren; Rupprecht, Charles E

    2009-11-27

    Despite progress in vaccine development in the past century the mechanisms behind immune responses elicited by rabies biologics or via natural infection remain largely unknown. In this study, we compared protection elicited by standard, early, or delayed prophylaxis with a reduced number of vaccine doses using inactivated and live-attenuated vaccines. Two-month-old Syrian hamsters, 4-week-old ICR mice or adult rhesus macaques were inoculated with canine rabies virus variants. Thereafter, prophylaxis was initiated 6h, 1, 2, 3, 4, 5, 6 or 7 days post-exposure (p.e.). One or several doses of inactivated (HDCV), or reverse genetically attenuated (live), or gamma-irradiated (inactivated)-ERAG333 vaccines were administered intramuscularly. The dynamics of virus spread were measured over time in the rodent models. Rabies virus reached the spinal cord at day 4 and brain at day 6 p.e. All hamsters succumbed in groups in which live ERAG333 was delayed until days 5 and 6 p.e. However, 78%, 44%, 56% and 22% of hamsters survived when one dose of live ERAG333 was administered 6h, 1, 2, 3, and 4 days p.e., respectively. Similarly, 67% survived when inactivated ERAG333 was administered at 24h p.e. All hamsters succumbed when standard prophylaxis (the Essen regimen) was delayed until days 3-6, but 67% and 33% of hamsters survived when PEP began 1 or 2 days p.e., respectively. Macaques were protected by one dose of attenuated ERAG333 at 24h p.e. The highly attenuated (live) and inactivated ERAG333 vaccines elicited potent protective immune responses, even when prophylaxis initiation was delayed. When 2-5 doses of commercial vaccine and HRIG were administered according to the Essen scheme, 89-100% of the animals survived. Reduced vaccine schedules provided efficacious intervention, regardless of the total number of vaccine doses administered.

  15. 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...

  16. A double-inactivated whole virus candidate SARS coronavirus vaccine stimulates neutralising and protective antibody responses.

    Science.gov (United States)

    Spruth, Martin; Kistner, Otfried; Savidis-Dacho, Helga; Hitter, Elisabeth; Crowe, Brian; Gerencer, Marijan; Brühl, Peter; Grillberger, Leopold; Reiter, Manfred; Tauer, Christa; Mundt, Wolfgang; Barrett, P Noel

    2006-01-30

    A double-inactivated, candidate whole virus vaccine against severe acute respiratory syndrome associated coronavirus (SARS-CoV) was developed and manufactured at large scale using fermenter cultures of serum protein free Vero cells. A two step inactivation procedure involving sequential formaldehyde and U.V. inactivation was utilised in order to ensure an extremely high safety margin with respect to residual infectivity. The immunogenicity of this double-inactivated vaccine was characterised in the mouse model. Mice that were immunised twice with the candidate SARS-CoV vaccine developed high antibody titres against the SARS-CoV spike protein and high levels of neutralising antibodies. The use of the adjuvant Al(OH)3 had only a minor effect on the immunogenicity of the vaccine. In addition, cell mediated immunity as measured by interferon-gamma and interleukin-4 stimulation, was elicited by vaccination. Moreover, the vaccine confers protective immunity as demonstrated by prevention of SARS-CoV replication in the respiratory tract of mice after intranasal challenge with SARS-CoV. Protection of mice was correlated to antibody titre against the SARS-CoV S protein and neutralising antibody titre.

  17. A purified inactivated Japanese encephalitis virus vaccine made in Vero cells.

    Science.gov (United States)

    Srivastava, A K; Putnak, J R; Lee, S H; Hong, S P; Moon, S B; Barvir, D A; Zhao, B; Olson, R A; Kim, S O; Yoo, W D; Towle, A C; Vaughn, D W; Innis, B L; Eckels, K H

    2001-08-14

    A second generation, purified, inactivated vaccine (PIV) against Japanese encephalitis (JE) virus was produced and tested in mice where it was found to be highly immunogenic and protective. The JE-PIV was made from an attenuated strain of JE virus propagated in certified Vero cells, purified, and inactivated with formalin. Its manufacture followed current GMP guidelines for the production of biologicals. The manufacturing process was efficient in generating a high yield of virus, essentially free of contaminating host cell proteins and nucleic acids. The PIV was formulated with aluminum hydroxide and administered to mice by subcutaneous inoculation. Vaccinated animals developed high-titered JE virus neutralizing antibodies in a dose dependent fashion after two injections. The vaccine protected mice against morbidity and mortality after challenge with live, virulent, JE virus. Compared with the existing licensed mouse brain-derived vaccine, JE-Vax, the Vero cell-derived JE-PIV was more immunogenic and as effective as preventing encephalitis in mice. The JE-PIV is currently being tested for safety and immunogenicity in volunteers.

  18. Immunogenicity of commercial, formaldehyde and binary ethylenimine inactivated Newcastle disease virus vaccines in specific pathogen free chickens

    Directory of Open Access Journals (Sweden)

    Razmaraii, N.

    2012-06-01

    Full Text Available Newcastle disease (ND is one of the most important diseases that affect birds; the epizootic nature of the disease has caused severe economic losses in the poultry industry worldwide. In this experiment ND virus (NDV was inactivated by two different chemicals binary ethylenimine (BEI and formaldehyde. Formaldehyde was used at 0.1%, while BEI was used at concentrations of 1 to 4 mM. NDV inactivation with BEI was done in various incubation temperatures and periods and the best result (30 °C, 4 mM BEI and 21 hrs treatment used as an experimental vaccine. Prepared inactivated NDV vaccines and a commercial vaccine were tested for their efficiency in generating humoral immune response in different groups of specific pathogen free (SPF chicks. Test groups received 0.2 ml formaldehyde inactivated NDV (NDVF, BEI inactivated NDV (NDVEI and Razi institute produced NDV vaccine (NDVR subcutaneously respectively. HI Log 2 total mean titer of NDVEI group (8.42 ± 0.12 were significantly higher than NDVF (7.64 ± 0.16 and NDVR (7.86 ± 0.11 groups (p<0.05. BEI-inactivated vaccine gave higher antibody titers than formaldehyde-inactivated vaccine and preserves both structural integrity and antigenicity of the virus. Thus, it might be possible to use these compounds as an inactivator agent for commercial NDV inactivated vaccines in future.

  19. Improved immunogenicity of Newcastle disease virus inactivated vaccine following DNA vaccination using Newcastle disease virus hemagglutinin-neuraminidase and fusion protein genes.

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    Firouzamandi, Masoumeh; Moeini, Hassan; Hosseini, Davood; Bejo, Mohd Hair; Omar, Abdul Rahman; Mehrbod, Parvaneh; Ideris, Aini

    2016-03-01

    The present study describes the development of DNA vaccines using the hemagglutinin-neuraminidase (HN) and fusion (F) genes from AF2240 Newcastle disease virus strain, namely pIRES/HN, pIRES/F and pIRES-F/HN. Transient expression analysis of the constructs in Vero cells revealed the successful expression of gene inserts in vitro. Moreover, in vivo experiments showed that single vaccination with the constructed plasmid DNA (pDNA) followed by a boost with inactivated vaccine induced a significant difference in enzyme-linked immunosorbent assay antibody levels (p < 0.05) elicited by either pIRES/F, pIRES/F+ pIRES/HN or pIRES-F/HN at one week after the booster in specific pathogen free chickens when compared with the inactivated vaccine alone. Taken together, these results indicated that recombinant pDNA could be used to increase the efficacy of the inactivated vaccine immunization procedure.

  20. 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

  1. Characterization of immune responses induced by inactivated, live attenuated and DNA vaccines against Japanese encephalitis virus in mice.

    Science.gov (United States)

    Li, Jieqiong; Chen, Hui; Wu, Na; Fan, Dongying; Liang, Guodong; Gao, Na; An, Jing

    2013-08-28

    Vaccination is the most effective countermeasure for protecting individuals from Japanese encephalitis virus (JEV) infection. There are two types of JEV vaccines currently used in China: the Vero cell-derived inactivated vaccine and the live attenuated vaccine. In this study, we characterized the immune response and protective efficacy induced in mice by the inactivated vaccine, live attenuated vaccine and the DNA vaccine candidate pCAG-JME, which expresses JEV prM-E proteins. We found that the live attenuated vaccine conferred 100% protection and resulted in the generation of high levels of specific anti-JEV antibodies and cytokines. The pCAG-JME vaccine induced protective immunity as well as the live attenuated vaccine. Unexpectedly, immunization with the inactivated vaccine only induced a limited immune response and partial protection, which may be due to the decreased activity of dendritic cells and the expansion of CD4+CD25+Foxp3+ regulatory T cells observed in these mice. Altogether, our results suggest that the live attenuated vaccine is more effective in providing protection against JEV infection than the inactivated vaccine and that pCAG-JME will be a potential JEV vaccine candidate. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. 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

  3. A single vaccination with an inactivated bovine respiratory syncytial virus vaccine primes the cellular immune response in calves with maternal antibody

    Directory of Open Access Journals (Sweden)

    Makoschey Birgit

    2010-01-01

    Full Text Available Abstract Background The efficacy of a single dose of an inactivated bovine respiratory syncytial virus (BRSV - Parainfluenaza type 3 (PI3 - Mannheimia haemolytica (Mh combination vaccine, in calves positive for maternal antibodies, was established in a BRSV infection study. Results As expected the single vaccination did not have any effect on the decline of BRSV-specific neutralising or ELISA antibody. The cellular immune system was however primed by the vaccination. In the vaccinated group virus excretion with nasal discharge was reduced, less virus could be re-isolated from lung tissues and the lungs were less affected. Conclusions These results indicate that a single vaccination with an inactivated BRSV vaccine was able to break through the maternal immunity and induce partial protection in very young calves. It can be speculated that the level and duration of protection will improve after the second dose of vaccine is administered. A two-dose basic vaccination schedule is recommended under field conditions.

  4. Colostral immunity in piglets from sows vaccinated with inactivated Aujeszky disease virus vaccine.

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    Wittmann, G; Jakubik, J

    1979-01-01

    Neutralizing antibodies against ADV were transmitted from sows, vaccinated with inactivated ADV adjuvanted with DEAE dextran, to their offspring via colostrum. The suckling piglets were protected by colostral immunity against contact infection with ADV at week 1 p.p., however, they were not protected against i.n. infection (10(8) TCD50). At 2 and 3 weeks p.p. all the piglets were protected against both contact infection and i.n. infection. At 4 weeks p.p. 50 per cent of the litter were protected against i.n. infection, in spite of very low antibody titres (1:2--1:4). The colostral antibodies did not interfere with active antibody response when the piglets were vaccinated with the inactivated vaccine from 2 weeks p.p. onward. Lymphocytes from suckling piglets of a vaccinated sow showed in vitro reactivity (enhanced 3H-thymidine incorporation) against ADV and BHK antigen, both contained in the vaccine used for the immunization of the sow.

  5. 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.

  6. 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.

  7. Generation of a recombinant rabies Flury LEP virus carrying an additional G gene creates an improved seed virus for inactivated vaccine production.

    Science.gov (United States)

    Tao, Lihong; Ge, Jinying; Wang, Xijun; Wen, Zhiyuan; Zhai, Hongyue; Hua, Tao; Zhao, Bolin; Kong, Dongni; Yang, Chinglai; Bu, Zhigao

    2011-09-25

    The rabies Flury Low Egg Passage virus (LEP) has been widely used as a seed virus to generate inactive vaccine. Here, we established a reverse genetic system for LEP and generated a recombinant LEP virus (rLEP-G) that carries two identical G genes. This recombinant virus showed similar properties to those of LEP with respect to in vitro growth, neurotropism index, and virulence in mice. rLEP-G produced 4.3-fold more G protein than did LEP in BHK-21 cells. The inactivated vaccine generated from rLEP-G induced significantly higher virus neutralization titers in mice and dogs than those produced in response to LEP-derived vaccine. Our results suggest that rLEP-G is an improved seed virus candidate for inactivated rabies virus vaccine manufacture.

  8. Generation of a recombinant rabies Flury LEP virus carrying an additional G gene creates an improved seed virus for inactivated vaccine production

    Directory of Open Access Journals (Sweden)

    Kong Dongni

    2011-09-01

    Full Text Available Abstract The rabies Flury Low Egg Passage virus (LEP has been widely used as a seed virus to generate inactive vaccine. Here, we established a reverse genetic system for LEP and generated a recombinant LEP virus (rLEP-G that carries two identical G genes. This recombinant virus showed similar properties to those of LEP with respect to in vitro growth, neurotropism index, and virulence in mice. rLEP-G produced 4.3-fold more G protein than did LEP in BHK-21 cells. The inactivated vaccine generated from rLEP-G induced significantly higher virus neutralization titers in mice and dogs than those produced in response to LEP-derived vaccine. Our results suggest that rLEP-G is an improved seed virus candidate for inactivated rabies virus vaccine manufacture.

  9. Efficacy of an inactivated virus vaccine for prevention of porcine parvovirus-induced reproductive failure.

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    Mengeling, W L; Brown, T T; Paul, P S; Gutekunst, D E

    1979-02-01

    Gilts vaccinated IM either once (4 gilts) or twice (2 gilts) with an acetylethyleneimine-inactivated porcine parvovirus (PPV) vaccine before they were bred were subsequently exposed intranasally and orally to virulent PPV at about the 40th day of gestation (from 37 to 43 days). At 2 weeks after vaccination, all had hemagglutination-inhibiting (HI) titers for PPV (from 20 to 80) which decreased by the time the immunity was challenged with virulent virus (from 10 to 40), but increased thereafter (from 160 to 1,280). Titers of singly and doubly vaccinated gilts were similar throughout the experiment. The gilts were killed at about the 84th day of gestation (from 80 to 87 days), and their litters were examined. Litters were comprised of 68 live fetuses and 1 dead fetus (7 to 14 fetuses/litter). Neither viral antigen, PPV, nor homologous HI antibody was found in any of the fetuses. In addition, 4 gilts were kept in contact with the vaccinated gilts and were treated similarly except for vaccination. These 4 gilts remained free of HI antibody until after they were exposed to virulent PPV during gestation. At the time the gilts were killed the titers were 1,280 to 2,560. Their litters were comprised of 11 live fetuses and 26 dead fetuses (8 to 11 fetuses/litter). Virus was isolated from fetuses of all litters. Viral antigen was found in 24 of the dead fetuses and 10 of the live fetuses. All infected live fetuses also had HI antibody for PPV. The 2 boars used to breed vaccinated and nonvaccinated gilts (usually each gilt was bred to each of the 2 boars), but not exposed to virulent PPV, remained free of HI antibody for PPV.

  10. Inactivation of 10(15) chimpanzee-infectious doses of hepatitis B virus during preparation of a heat-inactivated hepatitis B vaccine

    NARCIS (Netherlands)

    Lelie, P. N.; Reesink, H. W.; Niessen, J.; Brotman, B.; Prince, A. M.

    1987-01-01

    The safety of a plasma-derived hepatitis-B vaccine inactivated by two heating steps (90 sec at 103 degrees C followed by 10 hr pasteurization at 65 degrees C) was validated in chimpanzees; 10(3) chimpanzee-infectious doses (CID50) of hepatitis-B virus (HBV), subjected to the purification steps

  11. 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

  12. 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.

  13. 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 ...

  14. A combination vaccine comprising of inactivated enterovirus 71 and coxsackievirus A16 elicits balanced protective immunity against both viruses.

    Science.gov (United States)

    Cai, Yicun; Ku, Zhiqiang; Liu, Qingwei; Leng, Qibin; Huang, Zhong

    2014-05-01

    Enterovirus 71 (EV71) and coxsackievirus A16 (CA16) are the two major causative agents of hand, foot and mouth disease (HFMD), which is an infectious disease frequently occurring in children. A bivalent vaccine against both EV71 and CA16 is highly desirable. In the present study, we compare monovalent inactivated EV71, monovalent inactivated CA16, and a combination vaccine candidate comprising of both inactivated EV71 and CA16, for their immunogenicity and in vivo protective efficacy. The two monovalent vaccines were found to elicit serum antibodies that potently neutralized the homologous virus but had no or weak neutralization activity against the heterologous one; in contrast, the bivalent vaccine immunized sera efficiently neutralized both EV71 and CA16. More importantly, passive immunization with the bivalent vaccine protected mice against either EV71 or CA16 lethal infections, whereas the monovalent vaccines only prevented the homologous but not the heterologous challenges. Together, our results demonstrate that the experimental bivalent vaccine comprising of inactivated EV71 and CA16 induces a balanced protective immunity against both EV71 and CA16, and thus provide proof-of-concept for further development of multivalent vaccines for broad protection against HFMD. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Safety and efficacy in geese of a PER.C6-based inactivated West Nile virus vaccine

    NARCIS (Netherlands)

    Samina, Itzchak; Havenga, Menzo; Koudstaal, Wouter; Khinich, Yevgeny; Koldijk, Martin; Malkinson, Mertyn; Simanov, Michael; Perl, Shmuel; Gijsbers, Linda; Weverling, Gerrit Jan; Uytdehaag, Fons; Goudsmit, Jaap

    2007-01-01

    Studies were performed with an inactivated vaccine against the mosquito-borne flavivirus, West Nile virus (WNV). The mammalian cell line, PER.C6, was selected as the platform for WNV growth since both the neurovirulent strains NY99 and ISR98 that cause epidemics in humans and high mortality in

  16. Preparation of mucosal nanoparticles and polymer-based inactivated vaccine for Newcastle disease and H9N2 AI viruses

    Directory of Open Access Journals (Sweden)

    Heba M. El Naggar

    2017-02-01

    Full Text Available Aim: To develop a mucosal inactivated vaccines for Newcastle disease (ND and H9N2 viruses to protect against these viruses at sites of infections through mucosal immunity. Materials and Methods: In this study, we prepared two new formulations for mucosal bivalent inactivated vaccine formulations for Newcastle and Avian Influenza (H9N2 based on the use of nanoparticles and polymer adjuvants. The prepared vaccines were delivered via intranasal and spray routes of administration in specific pathogen-free chickens. Cell-mediated and humoral immune response was measured as well as challenge trial was carried out. In addition, ISA71 water in oil was also evaluated. Results: Our results showed that the use of spray route as vaccination delivery method of polymer and nanoparticles MontanideTM adjuvants revealed that it enhanced the cell mediated immune response as indicated by phagocytic activity, gamma interferon and interleukin 6 responses and induced protection against challenge with Newcastle and Avian Influenza (H9N2 viruses. Conclusion: The results of this study demonstrate the potentiality of polymer compared to nanoparticles adjuvantes when used via spray route. Mass application of such vaccines will add value to improve the vaccination strategies against ND virus and Avian influenza viruses.

  17. 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.

  18. 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).

  19. 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.

  20. Effect of Booster Vaccination with Inactivated Porcine Epidemic Diarrhea Virus on Neutralizing Antibody Response in Mammary Secretions.

    Science.gov (United States)

    Gillespie, Thomas; Song, Qinye; Inskeep, Megan; Stone, Suzanne; Murtaugh, Michael P

    Porcine epidemic diarrhea virus (PEDV) causes acute diarrhea, dehydration in pigs, and high mortality rates in piglets gilts through a feedback program before introduction into the sow herd. Since neutralizing antibodies in the gut are critical for protection against enteric viral infections such as PEDV, we evaluated the effect of a conditionally licensed, adjuvanted inactivated PEDV vaccine on neutralizing antibody levels in milk and colostrum in both naive and previously naturally exposed sow herds. The results illustrate that intramuscular vaccination increased neutralizing antibody titers, and anti-PEDV IgA and IgG in milk and colostrum of sows that were previously infected. Thus, inactivated PEDV vaccines may provide increased protection to piglets nursing on previously infected sows against exposure to PEDV through increased delivery of lactogenic neutralizing antibodies to the enteric site of infection.

  1. 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.

  2. 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.

    Science.gov (United States)

    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

  3. Protection of horses from West Nile virus Lineage 2 challenge following immunization with a whole, inactivated WNV lineage 1 vaccine.

    Science.gov (United States)

    Bowen, Richard A; Bosco-Lauth, Angela; Syvrud, Kevin; Thomas, Anne; Meinert, Todd R; Ludlow, Deborah R; Cook, Corey; Salt, Jeremy; Ons, Ellen

    2014-09-22

    Over the last years West Nile virus (WNV) lineage 2 has spread from the African to the European continent. This study was conducted to demonstrate efficacy of an inactivated, lineage 1-based, WNV vaccine (Equip WNV) against intrathecal challenge of horses with a recent isolate of lineage 2 WNV. Twenty horses, sero-negative for WNV, were enrolled and were randomly allocated to one of two treatment groups: an unvaccinated control group (T01, n=10) and a group administered with Equip WNV (T02, n=10). Horses were vaccinated at Day 0 and 21 and were challenged at day 42 with WNV lineage 2, Nea Santa/Greece/2010. Personnel performing clinical observations were blinded to treatment allocation. Sixty percent of the controls had to be euthanized after challenge compared to none of the vaccinates. A significantly lower percentage of the vaccinated animals showed clinical disease (two different clinical observations present on the same day) on six different days of study and the percentage of days with clinical disease was significantly lower in the vaccinated group. A total of 80% of the non-vaccinated horses showed viremia while only one vaccinated animal was positive by virus isolation on a single occasion. Vaccinated animals started to develop antibodies against WNV lineage 2 from day 14 (2 weeks after the first vaccination) and at day 42 (the time of onset of immunity) they had all developed a strong antibody response. Histopathology scores for all unvaccinated animals ranged from mild to very severe in each of the tissues examined (cervical spinal cord, medulla and pons), whereas in vaccinated horses 8 of 10 animals had no lesions and 2 had minimal lesions in one tissue. In conclusion, Equip WNV significantly reduced the number of viremic horses, the duration and severity of clinical signs of disease and mortality following challenge with lineage 2 WNV. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. An inactivated vaccine made from a U.S. field isolate of porcine epidemic disease virus is immunogenic in pigs as demonstrated by a dose-titration.

    Science.gov (United States)

    Collin, Emily A; Anbalagan, Srivishnupriya; Okda, Faten; Batman, Ron; Nelson, Eric; Hause, Ben M

    2015-03-15

    Porcine epidemic diarrhea virus (PEDV), a highly pathogenic and transmissible virus in swine, was first detected in the U.S. in May, 2013, and has caused tremendous losses to the swine industry. Due to the difficulty in isolating and growing this virus in cell culture, few vaccine studies using cell culture propagated PEDV have been performed on U.S. strains in pigs. Therefore, the objective of this study was to evaluate the humoral immune response to the selected inactivated PEDV vaccine candidate in a dose-titration manner. PEDV was isolated from a pig with diarrhea and complete genome sequencing found >99% nucleotide identity to other U.S. PEDV. Inactivated adjuvanted monovalent vaccines were administered intramuscularly to five week old pigs in a dose titration experimental design, ranging from 6.0-8.0 log10 tissue culture infective dose (TCID50/mL), to evaluate immunogenicity using a fluorescent foci neutralization assay (FFN), fluorescent microsphere immunoassay (FMIA), and enzyme-linked immunosorbent assay (ELISA) on sera. Pigs vaccinated with 8.0 log10 TCID50/mL inactivated virus showed significantly higher FFN titers as well as FMIA and ELISA values than 6.0 log10 TCID50/mL vaccinates and the negative controls. These results demonstrate the immunogenicity of a PEDV inactivated viral vaccine with a U.S. strain via dose-titration. A future vaccination-challenge study would illustrate the efficacy of an inactivated vaccine and help evaluate protective FFN titers and ELISA and FMIA responses.

  5. 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

  6. Immunogenicity and safety of a plasma-derived heat-inactivated hepatitis B vaccine (CLB). Studies in volunteers at a low risk of infection with hepatitis B virus

    NARCIS (Netherlands)

    Lelie, P. N.; Reesink, H. W.; de Jong-van Manen, S. T.; Dees, P. J.; Reerink-Brongers, E. E.

    1984-01-01

    The safety and immunogenicity of a plasma-derived heat-inactivated hepatitis B vaccine (CLB) were evaluated in 471 healthy human volunteers, who, both in their occupations and in their private lives, had been at minimal risk of being infected with hepatitis B virus. The first 202 individuals

  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. An adjuvanted, tetravalent dengue virus purified inactivated vaccine candidate induces long-lasting and protective antibody responses against dengue challenge in rhesus macaques.

    Science.gov (United States)

    Fernandez, Stefan; Thomas, Stephen J; De La Barrera, Rafael; Im-Erbsin, Rawiwan; Jarman, Richard G; Baras, Benoît; Toussaint, Jean-François; Mossman, Sally; Innis, Bruce L; Schmidt, Alexander; Malice, Marie-Pierre; Festraets, Pascale; Warter, Lucile; Putnak, J Robert; Eckels, Kenneth H

    2015-04-01

    The immunogenicity and protective efficacy of a candidate tetravalent dengue virus purified inactivated vaccine (TDENV PIV) formulated with alum or an Adjuvant System (AS01, AS03 tested at three different dose levels, or AS04) was evaluated in a 0, 1-month vaccination schedule in rhesus macaques. One month after dose 2, all adjuvanted formulations elicited robust and persisting neutralizing antibody titers against all four dengue virus serotypes. Most of the formulations tested prevented viremia after challenge, with the dengue serotype 1 and 2 virus strains administered at 40 and 32 weeks post-dose 2, respectively. This study shows that inactivated dengue vaccines, when formulated with alum or an Adjuvant System, are candidates for further development. © The American Society of Tropical Medicine and Hygiene.

  9. Systematic review of mucosal immunity induced by oral and inactivated poliovirus vaccines against virus shedding following oral poliovirus challenge.

    Directory of Open Access Journals (Sweden)

    Thomas R Hird

    Full Text Available Inactivated poliovirus vaccine (IPV may be used in mass vaccination campaigns during the final stages of polio eradication. It is also likely to be adopted by many countries following the coordinated global cessation of vaccination with oral poliovirus vaccine (OPV after eradication. The success of IPV in the control of poliomyelitis outbreaks will depend on the degree of nasopharyngeal and intestinal mucosal immunity induced against poliovirus infection. We performed a systematic review of studies published through May 2011 that recorded the prevalence of poliovirus shedding in stool samples or nasopharyngeal secretions collected 5-30 days after a "challenge" dose of OPV. Studies were combined in a meta-analysis of the odds of shedding among children vaccinated according to IPV, OPV, and combination schedules. We identified 31 studies of shedding in stool and four in nasopharyngeal samples that met the inclusion criteria. Individuals vaccinated with OPV were protected against infection and shedding of poliovirus in stool samples collected after challenge compared with unvaccinated individuals (summary odds ratio [OR] for shedding 0.13 (95% confidence interval [CI] 0.08-0.24. In contrast, IPV provided no protection against shedding compared with unvaccinated individuals (summary OR 0.81 [95% CI 0.59-1.11] or when given in addition to OPV, compared with individuals given OPV alone (summary OR 1.14 [95% CI 0.82-1.58]. There were insufficient studies of nasopharyngeal shedding to draw a conclusion. IPV does not induce sufficient intestinal mucosal immunity to reduce the prevalence of fecal poliovirus shedding after challenge, although there was some evidence that it can reduce the quantity of virus shed. The impact of IPV on poliovirus transmission in countries where fecal-oral spread is common is unknown but is likely to be limited compared with OPV.

  10. 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

  11. 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

  12. 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.

  13. 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.

  14. Live vaccinia-rabies virus recombinants, but not an inactivated rabies virus cell culture vaccine, protect B-lymphocyte-deficient A/WySnJ mice against rabies: considerations of recombinant defective poxviruses for rabies immunization of immunocompromised individuals.

    Science.gov (United States)

    Lodmell, Donald L; Esposito, Joseph J; Ewalt, Larry C

    2004-09-03

    Presently, commercially available cell culture rabies vaccines for humans and animals consist of the five inactivated rabies virus proteins. The vaccines elicit a CD4+ helper T-cell response and a humoral B-cell response against the viral glycoprotein (G) resulting in the production of virus neutralizing antibody. Antibody against the viral nucleoprotein (N) is also present, but the mechanism(s) of its protection is unclear. HIV-infected individuals with low CD4+ T-lymphocyte counts and individuals undergoing treatment with immunosuppressive drugs have an impaired neutralizing antibody response after pre- and post-exposure immunization with rabies cell culture vaccines. Here we show the efficacy of live vaccinia-rabies virus recombinants, but not a cell culture vaccine consisting of inactivated rabies virus, to elicit elevated levels of neutralizing antibody in B-lymphocyte deficient A/WySnJ mice. The cell culture vaccine also failed to protect the mice, whereas a single immunization of a vaccinia recombinant expressing the rabies virus G or co-expressing G and N equally protected the mice up to 18 months after vaccination. The data suggest that recombinant poxviruses expressing the rabies virus G, in particular replication defective poxviruses such as canarypox or MVA vaccinia virus that undergo abortive replication in non-avian cells, or the attenuated vaccinia virus NYVAC, should be evaluated as rabies vaccines in immunocompromised individuals.

  15. Production of a Dendritic Cell-Based Vaccine Containing Inactivated Autologous Virus for Therapy of Patients with Chronic Human Immunodeficiency Virus Type 1 Infection▿

    Science.gov (United States)

    Whiteside, Theresa L.; Piazza, Paolo; Reiter, Amanda; Stanson, Joanna; Connolly, Nancy C.; Rinaldo, Charles R.; Riddler, Sharon A.

    2009-01-01

    In preparation for a pilot clinical trial in patients with chronic human immunodeficiency virus type 1 (HIV-1) infection, a novel dendritic cell (DC)-based vaccine is being manufactured. The trial will test the hypothesis that isolated endogenous virus presented by DCs serves as a potent immunogen for activation of CD8+ and CD4+ T cells specific for a broad range of autologous HIV-1 antigens. Production of the vaccine under good manufacture practice conditions involves (i) autologous virus isolation; (ii) superinfection of CD4+ T cells with the virus; (iii) inactivation of the virus in CD4+ T cells, T-cell apoptosis, and coincubation of T cells with autologous DCs; and (iv) product testing and release. Endogenous virus was isolated from peripheral blood-derived CD4+ T cells of three HIV-1-positive subjects by coincubation with autologous OKT-3-stimulated CD4+ T cells. CD4+ T-cell supernatants were tested for p24 levels by enzyme-linked immunosorbent assay (>25 ng/ml) and for the 50% tissue culture infective doses (TCID50; which ranged from 4,642 to 46,416/ml on day 19 of culture). Autologous CD4+ T cells that were separated on immunobeads (>95% purity) and superinfected with virus-expressed p24 (28 to 54%) had TCID50 of >400/ml on days 5 to 10. Virus inactivation with psoralen (20 μg/ml) and UVB irradiation (312 nm) reduced the TCID50 of the supernatants from 199,986 to 11/ml (>99%). 7-Amino-actinomycin D-positive, annexin V-positive CD4+ T cells were fed to autologous DCs generated by using the Elutra cell separation system and the Aastrom system. Flow analysis showed that DC loading was complete in 24 h. On the basis of these translational results and experience with the generation of DCs from HIV-1-infected patients in a previous clinical trial, the Investigational New Drug application for clinical vaccination was submitted and approved by the FDA (application no. BB-IND-13137). PMID:19038780

  16. Production of a dendritic cell-based vaccine containing inactivated autologous virus for therapy of patients with chronic human immunodeficiency virus type 1 infection.

    Science.gov (United States)

    Whiteside, Theresa L; Piazza, Paolo; Reiter, Amanda; Stanson, Joanna; Connolly, Nancy C; Rinaldo, Charles R; Riddler, Sharon A

    2009-02-01

    In preparation for a pilot clinical trial in patients with chronic human immunodeficiency virus type 1 (HIV-1) infection, a novel dendritic cell (DC)-based vaccine is being manufactured. The trial will test the hypothesis that isolated endogenous virus presented by DCs serves as a potent immunogen for activation of CD8(+) and CD4(+) T cells specific for a broad range of autologous HIV-1 antigens. Production of the vaccine under good manufacture practice conditions involves (i) autologous virus isolation; (ii) superinfection of CD4(+) T cells with the virus; (iii) inactivation of the virus in CD4(+) T cells, T-cell apoptosis, and coincubation of T cells with autologous DCs; and (iv) product testing and release. Endogenous virus was isolated from peripheral blood-derived CD4(+) T cells of three HIV-1-positive subjects by coincubation with autologous OKT-3-stimulated CD4(+) T cells. CD4(+) T-cell supernatants were tested for p24 levels by enzyme-linked immunosorbent assay (>25 ng/ml) and for the 50% tissue culture infective doses (TCID(50); which ranged from 4,642 to 46,416/ml on day 19 of culture). Autologous CD4(+) T cells that were separated on immunobeads (>95% purity) and superinfected with virus-expressed p24 (28 to 54%) had TCID(50) of >400/ml on days 5 to 10. Virus inactivation with psoralen (20 microg/ml) and UVB irradiation (312 nm) reduced the TCID(50) of the supernatants from 199,986 to 11/ml (>99%). 7-Amino-actinomycin D-positive, annexin V-positive CD4(+) T cells were fed to autologous DCs generated by using the Elutra cell separation system and the Aastrom system. Flow analysis showed that DC loading was complete in 24 h. On the basis of these translational results and experience with the generation of DCs from HIV-1-infected patients in a previous clinical trial, the Investigational New Drug application for clinical vaccination was submitted and approved by the FDA (application no. BB-IND-13137).

  17. 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.

  18. 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

  19. Montanide IMS 1312 VG adjuvant enhances the efficacy of immersion vaccine of inactivated viral hemorrhagic septicemia virus (VHSV) in olive flounder, Paralichthys olivaceus.

    Science.gov (United States)

    Hwang, Jee Youn; Kwon, Mun-Gyeong; Kim, Yu Jin; Jung, Sung-Hee; Park, Myoung-Ae; Son, Maeng-Hyun

    2017-01-01

    Vaccination by immersion is suitable for mass vaccination of small size fish. However, no viral vaccine has been developed for immersion applications, because of low efficacy. In this study, we evaluated the efficacy and safety of immersion vaccine against viral hemorrhagic septicemia (VHS) containing Montanide IMS 1312 VG adjuvant in olive flounder (Paralichthys olivaceus). Healthy fish were vaccinated by an immersion method with a heat-inactivated FP-VHS2010-1 strain of VHS virus (VHSV) in combination with Montanide IMS 1312 VG for 5 min at 20 ± 2 °C. The control group was vaccinated with sterile PBS. No toxicity of immersion vaccine with Montanide IMS 1312 VG adjuvant was observed by hematological and histopathological analysis. Immersion vaccine with adjuvant enhanced gene expression of immune-associated genes, i.e., genes encoding interleukin (IL)-1β, IL-6, IL-8, and Toll-like receptor (TLR) 3. Relative percent survival (RPS) of fish was measured on weeks 4 and 8 post vaccination. In fish vaccinated with adjuvant, RPS was significantly higher than that of fish vaccinated without adjuvant. The results of the present study provide evidence that the VHSV immersion vaccine with Montanide IMS 1312 VG induces protective immunity in olive flounder against VHS. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. [Induction of biological protection in pigs against infection with Aujeszky disease virus by vaccination with large doses of live or inactivated vaccines].

    Science.gov (United States)

    Zuffa, A

    1986-02-01

    Pigs were inoculated against the Aujeszky's disease twice in a four-week interval. The dose of the live vaccine was 10(6) TKID50 and the titres of neutralizing antibodies were 1 : 16 to 1 : 128 in blood serum. Two weeks later the pigs were exposed to contact infection. Primary multiplication of the virus was observed on the mucous membranes of the nose and oropharynx and the virus was detected on the nasal mucous membrane within one to five days, the maximum infection titre values being 10(1.3) TKID50, and on the oropharyngeal mucous membrane within seven days, the maximum titres being up to 10(3.5) TKID50. In another group the pigs were inoculated with the same dose of attenuated virus or re-vaccinated with a dose of 10(8.5) TKID50, with neutralizing antibody titres of 1 : 256 to 1 : 1024 in blood serum. No viruses were detected on the nasal mucous membrane after contact infection and only trace amounts of the virus were found in the oropharynx within one to five days. Six piglets were inoculated in the same way but the infection was intranasal. The infective virus was detected on the nasal mucous membrane of only one piglet; however, trace amounts of the virus were found in the oropharynx of all the six piglets within three to nine days after infection. The nasal mucous membrane and oropharynx of the noninoculated control piglets exposed to intranasal infection were infectious until death and those of the contact-infected piglets remained so until the 14th day. At the intranasal infection of the piglets infected twice with a live or inactivated vaccine and slaughtered the 1st to 14th day after intranasal infection, the virus was replicated only in the place of primary multiplication without penetrating into the CNS and the internal organs. The intranasal infection of susceptible control piglets resulted in the dissemination of the infection via the neurogenic and lymphohaematogenic routes.

  1. 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.

  2. 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.

    Directory of Open Access Journals (Sweden)

    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.

  3. 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.

  4. 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.

  5. Early protection against foot-and-mouth disease virus in cattle using an inactivated vaccine formulated with Montanide ESSAI IMS D 12802 VG PR adjuvant.

    Science.gov (United States)

    Quattrocchi, V; Pappalardo, J S; Langellotti, C; Smitsaart, E; Fondevila, N; Zamorano, P

    2014-04-17

    Foot and mouth disease is an acute disease of cattle with a broad distribution around the world. Due to the fast spread of FMDV infections, control measures must be applied immediately after an outbreak, such as the use of vaccines that induce fast protection. Previously, it was shown that mice vaccinated with FMD inactivated virus (iFMDV) formulated with Montanide™ ESSAI IMS D 12802 VG PR adjuvant (802-iFMDV) were protected when they were challenged 4 and 7 days post-vaccination (dpv) with homologous virus. In this work, we describe the successful use of this formulation in cattle. In addition, adjuvant Montanide™ IMS 1313 VG NPR was also tested. 802-iFMDV vaccine was able to confer 100% protection against viral challenge at 4 and 7 dpv, while eliciting low antibody levels, at 7 dpv. 1313-iFMDV vaccine induced protection in 60% of cattle. At 4 dpv, 1313-iFMDV vaccinated animals presented increased levels of IFNγ but not of macrophages. At 4 and 7 dpv, macrophages, IFNγ, nasal IgA and IgG1 antibodies against FMDV, and opsonophagocytosis were increased in animals vaccinated with 802-iFMDV indicating that these phenomena could be involved in protection.It is the first time that total protection against FMDV at early stages post-vaccination is reported using a single dose of the formulation iFMDV plus Montanide™ ESSAI D IMS 12802 VG PR adjuvant. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Zika Virus Vaccine Development.

    Science.gov (United States)

    Morabito, Kaitlyn M; Graham, Barney S

    2017-12-16

    The emergence of Zika virus in Brazil and its association with microcephaly and Guillain-Barré syndrome led to accelerated vaccine development efforts. Based on prior flavivirus vaccine development programs, knowledge of flavivirus particle structure, definition of E dimers as the key antigenic target, and deep understanding of neutralizing mechanisms, multiple vaccine strategies have advanced to the stage of clinical evaluation with unprecedented speed. These include nucleic acid (DNA and messenger RNA), whole-inactivated virus, live-attenuated or chimeric virus, and protein or viruslike particle vaccines. Within a year from the declaration by the World Health Organization of Zika virus as a Public Health Emergency of International Concern, multiple vaccine candidates entered clinical trials, now totaling 7 products with an additional 40-plus candidate vaccines in preclinical development. The rapid progress in vaccine development demonstrates the capacity of governments, public health organizations, and the scientific community to respond to pandemic threats when sufficient prior knowledge exists, emergency funding is made available, and interagency cooperation is achieved and serves as a paradigm for preparing for future emerging infectious diseases. Published by Oxford University Press for the Infectious Diseases Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  7. Immunogenicity of UV-inactivated measles virus

    International Nuclear Information System (INIS)

    Zahorska, R.; Mazur, N.; Korbecki, M.

    1978-01-01

    By means of the antigen extinction limit test it was shown that a triple dose vaccination of guinea pigs with UV-inactivated measles virus gave better results, than a single dose vaccination which was proved by the very low immunogenicity index. For both vaccination schemes (single and triple) the immune response was only sligthly influenced by a change of dose from 10 5 to 10 6 HadU 50 /ml or by the addition of aluminum adjuvant. In the antigen extinction limit test the antibody levels were determined by two methods (HIT and NT) the results of which were statistically equivalent. The UV-inactivated measles virus was also found to induce hemolysis-inhibiting antibodies. (orig.) [de

  8. Dengue virus vaccine development.

    Science.gov (United States)

    Yauch, Lauren E; Shresta, Sujan

    2014-01-01

    Dengue virus (DENV) is a significant cause of morbidity and mortality in tropical and subtropical regions, causing hundreds of millions of infections each year. Infections range from asymptomatic to a self-limited febrile illness, dengue fever (DF), to the life-threatening dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). The expanding of the habitat of DENV-transmitting mosquitoes has resulted in dramatic increases in the number of cases over the past 50 years, and recent outbreaks have occurred in the United States. Developing a dengue vaccine is a global health priority. DENV vaccine development is challenging due to the existence of four serotypes of the virus (DENV1-4), which a vaccine must protect against. Additionally, the adaptive immune response to DENV may be both protective and pathogenic upon subsequent infection, and the precise features of protective versus pathogenic immune responses to DENV are unknown, complicating vaccine development. Numerous vaccine candidates, including live attenuated, inactivated, recombinant subunit, DNA, and viral vectored vaccines, are in various stages of clinical development, from preclinical to phase 3. This review will discuss the adaptive immune response to DENV, dengue vaccine challenges, animal models used to test dengue vaccine candidates, and historical and current dengue vaccine approaches. © 2014 Elsevier Inc. All rights reserved.

  9. Long-term administration of a commercial porcine reproductive and respiratory syndrome virus (PRRSV)-inactivated vaccine in PRRSV-endemically infected sows.

    Science.gov (United States)

    Papatsiros, V G; Alexopoulos, C; Kritas, S K; Koptopoulos, G; Nauwynck, H J; Pensaert, M B; Kyriakis, S C

    2006-08-01

    The purpose of this study was to investigate the safety and efficacy of a commercial European porcine reproductive and respiratory syndrome virus (PRRSV)-inactivated vaccine after 18-month use in gilts/sows at a farm with high seroprevalence. In a farrow-to-finish farm with 1100 sows, all sows and gilts were systematically vaccinated with the PRRS-inactivated PROGRESSIS vaccine for a period of 18 months. Farm's reproductive and litter characteristics were longitudinally recorded for this period and historically compared with those of the year prior to vaccination. Serology, employing immunoperoxidase monolayer assay, had confirmed a high prevalence of PRRS-specific antibodies in most age groups within the farm prior to vaccination. Seroprevalence during the experiment ranged between 0% and 100% in weaners and growers, but remained at stable high levels (> 93%) in finishing pigs and gilts throughout all 2-year period of serology measurements. No local or systemic vaccine side effects were noted throughout the trial period. Vaccinations had resulted over time in a significant improvement of sow reproductive performance (e.g. reduction of premature farrowings, abortions and increase of farrowing rate) and litter characteristics (e.g. increase of the number of live born and weaned pigs and decrease of stillborn, mummified, weak and splay-legged piglets). It has also been observed that the higher the degree of immunization of a sow, the better the improvement of her reproductive parameters. Sows after vaccination have shown improved characteristics compared to homoparous sows prior to the application of vaccinations in the farm.

  10. Inactivated simian immunodeficiency virus vaccine failed to protect rhesus macaques from intravenous or genital mucosal infection but delayed disease in intravenously exposed animals

    International Nuclear Information System (INIS)

    Sutjipto, S.; Pedersen, N.C.; Miller, C.J.; Gardner, M.B.; Hanson, C.V.; Gettie, A.; Jennings, M.; Higgins, J.; Marx, P.A.

    1990-01-01

    Eight rhesus macaques were immunized four times over a period of 8 months with a psoralen-UV-light-inactivated whole simian immunodeficiency virus vaccine adjuvanted with threonyl muramyl dipeptide. Eight unvaccinated control animals received adjuvant alone. Only the vaccinated animals made antibodies before challenge exposure to the viral core and envelope as determined by Western blotting (immunoblotting) and virus-neutralizing antibodies. Ten days after the final immunization, one-half of the vaccinated and nonvaccinated monkeys were challenged exposed intravenously (i.v.) and one-half were challenge exposed via the genital mucosa with virulent simian immunodeficiency virus. All of the nonvaccinated control monkeys became persistently infected. In spite of preexisting neutralizing antibodies and an anamnestic antibody response, all of the immunized monkeys also became persistently infected. However, there was evidence that the clinical course in immunized i.v. infected animals was delayed. All four mock-vaccinated i.v. challenge-exposed animals died with disease from 3 to 9 months postchallenge. In contrast, only one of four vaccinated i.v. challenge-exposed monkeys had died by 11 months postchallenge

  11. 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.

  12. 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

  13. The global introduction of inactivated polio vaccine can circumvent the oral polio vaccine paradox

    NARCIS (Netherlands)

    Heinsbroek, E.; Ruitenberg, E.J.

    2010-01-01

    This literature review identifies the factors that influence the decision to introduce inactivated polio vaccine (IPV) in developing countries as opposed to the policy of vaccine cessation. Attenuated viruses in the oral polio vaccine (OPV) can replicate, revert to neurovirulence and become

  14. A proposal for an alternative quality control test procedure for inactivated vaccines against food-and-mouth disease virus.

    Science.gov (United States)

    Molin-Capeti, K C; Sepulveda, L; Terra, F; Torres-Pioli, M F; Costa-Casagrande, T; França, S C; Thomaz-Soccol, V

    2013-02-18

    Foot-and-mouth disease (FMD) control in Brazil includes a strict mandatory vaccination program with vaccines produced in certified laboratories subject to inspection by the Brazilian Ministry of Agriculture, Livestock, and Food Supply (MAPA). The FMD vaccine's potency is tested through antibodies titration against structural viral proteins in sera from cattle that have not had any exposure to food-and-mouth disease virus (FMDV), at 28 days post-vaccination. Biological product testing using large animals is expensive and unwieldy. Thus, alternative testing procedures using laboratory animals have been proposed for quality control of these products. Such biological methods for vaccine evaluation using animals from vivarium facilities can have a significant impact through reduced costs, easier handling, and shorter testing times. The present study was designed to access Balb/C mice's humoral immune responses to a FMDV experimental vaccine, the composition of which contains three virus serotypes of FMDV (O1 Campos, A24 Cruzeiro, and C3 Indaial). Balb/C mice were immunized at doses that were 5% and 10% of the vaccine volume administered in cattle. Immunized mice had their antibody titers probed at 14, 21, and 28 DPV (days post vaccination). The results obtained were compared to those previously known from cattle's immune responses to the FMDV vaccine. An adequate immune response to the vaccine was seen with 10% formulation at 21 DPV. The study results are encouraging and indicate that the mouse model can be used for quality control in experimental vaccine testing. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. 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.

  16. Experience of vaccination with inactivated poliomyelitis vaccines in Iceland.

    Science.gov (United States)

    Gudnadóttir, M

    1981-01-01

    Iceland, as a few other European countries, has used inactivated vaccine against poliomyelitis from the beginning in 1956. No cases of paralytic polio occurred since 1960. For 17 years neither isolations of poliovirus nor suspected cases of the clinical disease have been recorded. Studies on neutralizing antibodies in sera of vaccinees were not too encouraging after 4 injections. A 5th vaccination of IPV was therefore given to those children who lacked antibodies to any type of poliovirus. One month after the 5th injection 70% had antibodies against all 3 types of poliovirus and only 2% lacked antibodies against both types 1 and 3. In countries where no virus to boost immunity exists any longer during the life of an individual it may be necessary to secure booster effects at regular intervals after primary vaccination and later in life. This will be included in the vaccination schedule against polio in Iceland.

  17. An Inactivated Rabies Virus-Based Ebola Vaccine, FILORAB1, Adjuvanted With Glucopyranosyl Lipid A in Stable Emulsion Confers Complete Protection in Nonhuman Primate Challenge Models.

    Science.gov (United States)

    Johnson, Reed F; Kurup, Drishya; Hagen, Katie R; Fisher, Christine; Keshwara, Rohan; Papaneri, Amy; Perry, Donna L; Cooper, Kurt; Jahrling, Peter B; Wang, Jonathan T; Ter Meulen, Jan; Wirblich, Christoph; Schnell, Matthias J

    2016-10-15

    The 2013-2016 West African Ebola virus (EBOV) disease outbreak was the largest filovirus outbreak to date. Over 28 000 suspected, probable, or confirmed cases have been reported, with a 53% case-fatality rate. The magnitude and international impact of this EBOV outbreak has highlighted the urgent need for a safe and efficient EBOV vaccine. To this end, we demonstrate the immunogenicity and protective efficacy of FILORAB1, a recombinant, bivalent, inactivated rabies virus-based EBOV vaccine, in rhesus and cynomolgus monkeys. Our results demonstrate that the use of the synthetic Toll-like receptor 4 agonist glucopyranosyl lipid A in stable emulsion (GLA-SE) as an adjuvant increased the efficacy of FILORAB1 to 100% protection against lethal EBOV challenge, with no to mild clinical signs of disease. Furthermore, all vaccinated subjects developed protective anti-rabies virus antibody titers. Taken together, these results support further development of FILORAB1/GLA-SE as an effective preexposure EBOV vaccine. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  18. Preliminary aggregate safety and immunogenicity results from three trials of a purified inactivated Zika virus vaccine candidate: phase 1, randomised, double-blind, placebo-controlled clinical trials.

    Science.gov (United States)

    Modjarrad, Kayvon; Lin, Leyi; George, Sarah L; Stephenson, Kathryn E; Eckels, Kenneth H; De La Barrera, Rafael A; Jarman, Richard G; Sondergaard, Erica; Tennant, Janice; Ansel, Jessica L; Mills, Kristin; Koren, Michael; Robb, Merlin L; Barrett, Jill; Thompson, Jason; Kosel, Alison E; Dawson, Peter; Hale, Andrew; Tan, C Sabrina; Walsh, Stephen R; Meyer, Keith E; Brien, James; Crowell, Trevor A; Blazevic, Azra; Mosby, Karla; Larocca, Rafael A; Abbink, Peter; Boyd, Michael; Bricault, Christine A; Seaman, Michael S; Basil, Anne; Walsh, Melissa; Tonwe, Veronica; Hoft, Daniel F; Thomas, Stephen J; Barouch, Dan H; Michael, Nelson L

    2017-12-04

    A safe, effective, and rapidly scalable vaccine against Zika virus infection is needed. We developed a purified formalin-inactivated Zika virus vaccine (ZPIV) candidate that showed protection in mice and non-human primates against viraemia after Zika virus challenge. Here we present the preliminary results in human beings. We did three phase 1, placebo-controlled, double-blind trials of ZPIV with aluminium hydroxide adjuvant. In all three studies, healthy adults were randomly assigned by a computer-generated list to receive 5 μg ZPIV or saline placebo, in a ratio of 4:1 at Walter Reed Army Institute of Research, Silver Spring, MD, USA, or of 5:1 at Saint Louis University, Saint Louis, MO, USA, and Beth Israel Deaconess Medical Center, Boston, MA, USA. Vaccinations were given intramuscularly on days 1 and 29. The primary objective was safety and immunogenicity of the ZPIV candidate. We recorded adverse events and Zika virus envelope microneutralisation titres up to day 57. These trials are registered at ClinicalTrials.gov, numbers NCT02963909, NCT02952833, and NCT02937233. We enrolled 68 participants between Nov 7, 2016, and Jan 25, 2017. One was excluded and 67 participants received two injections of Zika vaccine (n=55) or placebo (n=12). The vaccine caused only mild to moderate adverse events. The most frequent local effects were pain (n=40 [60%]) or tenderness (n=32 [47%]) at the injection site, and the most frequent systemic reactogenic events were fatigue (29 [43%]), headache (26 [39%]), and malaise (15 [22%]). By day 57, 52 (92%) of vaccine recipients had seroconverted (microneutralisation titre ≥1:10), with peak geometric mean titres seen at day 43 and exceeding protective thresholds seen in animal studies. The ZPIV candidate was well tolerated and elicited robust neutralising antibody titres in healthy adults. Departments of the Army and Defense and National Institute of Allergy and Infectious Diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Adjuvanted poly(lactic-co-glycolic) acid nanoparticle-entrapped inactivated porcine reproductive and respiratory syndrome virus vaccine elicits cross-protective immune response in pigs

    Science.gov (United States)

    Binjawadagi, Basavaraj; Dwivedi, Varun; Manickam, Cordelia; Ouyang, Kang; Wu, Yun; Lee, Ly James; Torrelles, Jordi B; Renukaradhya, Gourapura J

    2014-01-01

    Porcine reproductive and respiratory syndrome (PRRS), caused by the PRRS virus (PRRSV), is an economically devastating disease, causing daily losses of approximately $3 million to the US pork industry. Current vaccines have failed to completely prevent PRRS outbreaks. Recently, we have shown that poly(lactic-co-glycolic) acid (PLGA) nanoparticle-entrapped inactivated PRRSV vaccine (NP-KAg) induces a cross-protective immune response in pigs. To further improve its cross-protective efficacy, the NP-KAg vaccine formulation was slightly modified, and pigs were coadministered the vaccine twice intranasally with a potent adjuvant: Mycobacterium tuberculosis whole-cell lysate. In vaccinated virulent heterologous PRRSV-challenged pigs, the immune correlates in the blood were as follows: 1) enhanced PRRSV-specific antibody response with enhanced avidity of both immunoglobulin (Ig)-G and IgA isotypes, associated with augmented virus-neutralizing antibody titers; 2) comparable and increased levels of virus-specific IgG1 and IgG2 antibody subtypes and production of high levels of both T-helper (Th)-1 and Th2 cytokines, indicative of a balanced Th1–Th2 response; 3) suppressed immunosuppressive cytokine response; 4) increased frequency of interferon-γ+ lymphocyte subsets and expanded population of antigen-presenting cells; and most importantly 5) complete clearance of detectable replicating challenged heterologous PRRSV and close to threefold reduction in viral ribonucleic acid load detected in the blood. In conclusion, intranasal delivery of adjuvanted NP-KAg vaccine formulation to growing pigs elicited a broadly cross-protective immune response, showing the potential of this innovative vaccination strategy to prevent PRRS outbreaks in pigs. A similar approach to control other respiratory diseases in food animals and humans appears to be feasible. PMID:24493925

  20. Production of a Dendritic Cell-Based Vaccine Containing Inactivated Autologous Virus for Therapy of Patients with Chronic Human Immunodeficiency Virus Type 1 Infection▿

    OpenAIRE

    Whiteside, Theresa L.; Piazza, Paolo; Reiter, Amanda; Stanson, Joanna; Connolly, Nancy C.; Rinaldo, Charles R.; Riddler, Sharon A.

    2008-01-01

    In preparation for a pilot clinical trial in patients with chronic human immunodeficiency virus type 1 (HIV-1) infection, a novel dendritic cell (DC)-based vaccine is being manufactured. The trial will test the hypothesis that isolated endogenous virus presented by DCs serves as a potent immunogen for activation of CD8+ and CD4+ T cells specific for a broad range of autologous HIV-1 antigens. Production of the vaccine under good manufacture practice conditions involves (i) autologous virus is...

  1. Viruses - from pathogens to vaccine carriers.

    Science.gov (United States)

    Small, Juliana C; Ertl, Hildegund C J

    2011-10-01

    Vaccination is mankind's greatest public health success story. By now vaccines to many of the viruses that once caused fatal childhood diseases are routinely used throughout the world. Traditional methods of vaccine development through inactivation or attenuation of viruses have failed for some of the most deadly human pathogens, necessitating new approaches. Genetic modification of viruses not only allows for their attenuation but also for incorporation of sequences from other viruses, turning one pathogen into a vaccine carrier for another. Recombinant viruses have pros and cons as vaccine carriers, as discussed below using vectors based on adenovirus, herpesvirus, flavivirus, and rhabdovirus as examples.

  2. 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

  3. 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.

  4. 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...

  5. Development of Zika Virus Vaccines

    Directory of Open Access Journals (Sweden)

    Huda Makhluf

    2018-01-01

    Full Text Available Zika virus (ZIKV is a mosquito-borne flavivirus that emerged as a global threat following the most recent outbreak in Brazil in 2015. ZIKV infection of pregnant women is associated with fetal abnormalities such as microcephaly, and infection of adults can lead to Guillain–Barré syndrome, an autoimmune disease characterized by neurological deficits. Although there are currently licensed vaccines for other flaviviruses, there remains an urgent need for preventative vaccines against ZIKV infection. Herein we describe the current efforts to accelerate the development of ZIKV vaccines using various platforms, including live attenuated virus, inactivated virus, DNA and RNA, viral vectors, and in silico-predicted immunogenic viral epitopes. Many of these approaches have leveraged lessons learned from past experience with Dengue and other flavivirus vaccines.

  6. ERADIKASI POLIO DAN IPV (INACTIVATED POLIO VACCINE

    Directory of Open Access Journals (Sweden)

    Gendrowahyuhono Gendrowahyuhono

    2012-09-01

    Full Text Available In the year 1988, World Health Organization (WHO claims that polio viruses should be eradicated after year 2000. However, until year 2010 the world have not been free from polio viruses circulation. So many effort had been achieved and it is estimated that the world will be free from polio virus after the year 2013. Control of poliomyelitis in Indonesia has been commenced since 1982 with routine immunization of polio program and the National Immunization Days (NID has been commenced since 1995,1996,2005 and 2006. When the world is free from polio virus, WHO suggests several alternative effort to maintain the world free from polio viruses : I stop the OPV (Oral Polio Vaccine and no polio immunization, 2 stop OPV and stock pile mOPV (monovalent OPV, 3 use OPV and IPV (Inactivated Polio Vaccine in a certain times, 4 use IPV only in a certain times. IPV has been used routinely in develop countries but has not been used in the developing countries. Several studies in development countries has been conducted, but had not been done in the developing countries. Indonesia collaboration with WHO has conducted the study of IPV in Yogyakarta Province since year 2002 until year 2010. The overall aim of the study is to compile the necessary data that will inform global and national decision-making regarding future polio immunization policies for the OPV cessation era. The data generated from the study will be particularly important to make decisions regarding optimal IPV use in developing tropical countries. It is unlikely that this data can be assembled through other means than through this study. The tentative result of the study shows that OPV immunization coverage in the year 2004 is 99% in four district and 93 % in the Yogyakarta city. Environment surveillance shows that there are 65.7% polio virus detected from 137 sewage samples pre IPV swich, and 4.8% polio virus detected from 83 sewage samples post IPV swich. Survey polio antibody serologis shows

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. 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

  12. Safety and immunogenicity of inactivated varicella-zoster virus vaccine in adults with hematologic malignancies receiving treatment with anti-CD20 monoclonal antibodies.

    Science.gov (United States)

    Parrino, Janie; McNeil, Shelly A; Lawrence, Steven J; Kimby, Eva; Pagnoni, Marco F; Stek, Jon E; Zhao, Yanli; Chan, Ivan S F; Kaplan, Susan S

    2017-03-27

    Immunocompromised patients can experience significant morbidity and occasional mortality from complications associated with herpes zoster (HZ), but live attenuated HZ vaccine is contraindicated for these patients. Inactivated zoster vaccine (ZV IN ) is in development for prevention of HZ in immunocompromised patients. However, there are limited data in the literature regarding the effect of anti-CD20 monoclonal antibodies on vaccine-related cell-mediated immune response. This study evaluated safety and immunogenicity of ZV IN in patients with hematologic malignancies (HM) receiving anti-CD20 monoclonal antibodies (alone or in combination chemotherapy regimens) and not likely to undergo hematopoietic cell transplant (HCT) (n=80). This was an open-label, single-arm, multicenter Phase I study (NCT01460719) of a 4-dose ZV IN regimen (∼30days between doses) in patients ⩾18years old. Blood samples were collected prior to dose 1 and 28days Postdose 4 to measure varicella zoster virus (VZV)-specific T-cell responses using interferon-γ enzyme-linked immunospot (IFN-γ ELISPOT). The primary hypothesis was that ZV IN would elicit significant VZV-specific immune responses at ∼28days Postdose 4, with a geometric fold rise (GMFR) >1.0. All vaccinated patients were evaluated for adverse events (AE) through 28days Postdose 4. ZV IN elicited a statistically significant VZV-specific immune response measured by IFN-γ ELISPOT at 28days Postdose 4 (GMFR=4.34 [90% CI:3.01, 6.24], p-valuevaccination by the investigator. Frequencies of AEs did not increase with subsequent doses of vaccine. No recipient of ZV IN had rash polymerase chain reaction (PCR) positive for VZV vaccine strain. In adults with HM receiving anti-CD20 monoclonal antibodies, ZV IN was well-tolerated and elicited statistically significant VZV-specific T-cell responses ∼28days Postdose 4. CLINICALTRIALS.GOV identifier: NCT01460719. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. 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.

  14. Dengue virus photo-inactivated in presence of 1,5-iodonaphthylazide (INA) or AMT, a psoralen compound (4′-aminomethyl-trioxsalen) is highly immunogenic in mice

    Science.gov (United States)

    Raviprakash, Kanakatte; Sun, Peifang; Raviv, Yossef; Luke, Thomas; Martin, Nicholas; Kochel, Tadeusz

    2013-01-01

    Two novel methods of dengue virus inactivation using iodonaphthyl azide (INA) and aminomethyl trioxsalen (AMT) were compared with traditional virus inactivation by formaldehyde. The AMT inactivated dengue-2 virus retained its binding to a panel of 5 monoclonal antibodies specific for dengue-2 envelope protein, whereas inactivation by formaldehyde and INA led to 30–50% decrease in binding. All three inactivated viruses elicited high level virus neutralizing antibodies in vaccinated mice. However, only mice vaccinated with AMT inactivated virus mounted T cell responses similar to live, uninactivated virus. PMID:23835446

  15. An inactivated yellow fever 17DD vaccine cultivated in Vero cell cultures.

    Science.gov (United States)

    Pereira, Renata C; Silva, Andrea N M R; Souza, Marta Cristina O; Silva, Marlon V; Neves, Patrícia P C C; Silva, Andrea A M V; Matos, Denise D C S; Herrera, Miguel A O; Yamamura, Anna M Y; Freire, Marcos S; Gaspar, Luciane P; Caride, Elena

    2015-08-20

    Yellow fever is an acute infectious disease caused by prototype virus of the genus Flavivirus. It is endemic in Africa and South America where it represents a serious public health problem causing epidemics of hemorrhagic fever with mortality rates ranging from 20% to 50%. There is no available antiviral therapy and vaccination is the primary method of disease control. Although the attenuated vaccines for yellow fever show safety and efficacy it became necessary to develop a new yellow fever vaccine due to the occurrence of rare serious adverse events, which include visceral and neurotropic diseases. The new inactivated vaccine should be safer and effective as the existing attenuated one. In the present study, the immunogenicity of an inactivated 17DD vaccine in C57BL/6 mice was evaluated. The yellow fever virus was produced by cultivation of Vero cells in bioreactors, inactivated with β-propiolactone, and adsorbed to aluminum hydroxide (alum). Mice were inoculated with inactivated 17DD vaccine containing alum adjuvant and followed by intracerebral challenge with 17DD virus. The results showed that animals receiving 3 doses of the inactivated vaccine (2 μg/dose) with alum adjuvant had neutralizing antibody titers above the cut-off of PRNT50 (Plaque Reduction Neutralization Test). In addition, animals immunized with inactivated vaccine showed survival rate of 100% after the challenge as well as animals immunized with commercial attenuated 17DD vaccine. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. 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

  17. Mucosal vaccination with formalin-inactivated avian metapneumovirus subtype C does not protect turkeys following intranasal challenge.

    Science.gov (United States)

    Kapczynski, Darrell R; Perkins, Laura L; Sellers, Holly S

    2008-03-01

    Studies were performed to determine if mucosal vaccination with inactivated avian metapneumovirus (aMPV) subtype C protected turkey poults from clinical disease and virus replication following mucosal challenge. Decreases in clinical disease were not observed in vaccinated groups, and the vaccine failed to inhibit virus replication in the tracheas of 96% of vaccinated birds. Histopathologically, enhancement of pulmonary lesions following virus challenge was associated with birds receiving the inactivated aMPV vaccine compared to unvaccinated birds. As determined by an enzyme-linked immunosorbent assay (ELISA), all virus-challenged groups increased serum immunoglobulin (Ig) G and IgA antibody production against the virus following challenge; however, the unvaccinated aMPV-challenged group displayed the highest increases in virus-neutralizing antibody. On the basis of these results it is concluded that intranasal vaccination with inactivated aMPV does not induce protective immunity, reduce virus shedding, or result in decreased histopathologic lesions.

  18. Photodynamic inactivation of mammalian viruses and bacteriophages.

    Science.gov (United States)

    Costa, Liliana; Faustino, Maria Amparo F; Neves, Maria Graça P M S; Cunha, Angela; Almeida, Adelaide

    2012-07-01

    Photodynamic inactivation (PDI) has been used to inactivate microorganisms through the use of photosensitizers. The inactivation of mammalian viruses and bacteriophages by photosensitization has been applied with success since the first decades of the last century. Due to the fact that mammalian viruses are known to pose a threat to public health and that bacteriophages are frequently used as models of mammalian viruses, it is important to know and understand the mechanisms and photodynamic procedures involved in their photoinactivation. The aim of this review is to (i) summarize the main approaches developed until now for the photodynamic inactivation of bacteriophages and mammalian viruses and, (ii) discuss and compare the present state of the art of mammalian viruses PDI with phage photoinactivation, with special focus on the most relevant mechanisms, molecular targets and factors affecting the viral inactivation process.

  19. Photodynamic Inactivation of Mammalian Viruses and Bacteriophages

    Science.gov (United States)

    Costa, Liliana; Faustino, Maria Amparo F.; Neves, Maria Graça P. M. S.; Cunha, Ângela; Almeida, Adelaide

    2012-01-01

    Photodynamic inactivation (PDI) has been used to inactivate microorganisms through the use of photosensitizers. The inactivation of mammalian viruses and bacteriophages by photosensitization has been applied with success since the first decades of the last century. Due to the fact that mammalian viruses are known to pose a threat to public health and that bacteriophages are frequently used as models of mammalian viruses, it is important to know and understand the mechanisms and photodynamic procedures involved in their photoinactivation. The aim of this review is to (i) summarize the main approaches developed until now for the photodynamic inactivation of bacteriophages and mammalian viruses and, (ii) discuss and compare the present state of the art of mammalian viruses PDI with phage photoinactivation, with special focus on the most relevant mechanisms, molecular targets and factors affecting the viral inactivation process. PMID:22852040

  20. Photodynamic Inactivation of Mammalian Viruses and Bacteriophages

    Directory of Open Access Journals (Sweden)

    Liliana Costa

    2012-06-01

    Full Text Available Photodynamic inactivation (PDI has been used to inactivate microorganisms through the use of photosensitizers. The inactivation of mammalian viruses and bacteriophages by photosensitization has been applied with success since the first decades of the last century. Due to the fact that mammalian viruses are known to pose a threat to public health and that bacteriophages are frequently used as models of mammalian viruses, it is important to know and understand the mechanisms and photodynamic procedures involved in their photoinactivation. The aim of this review is to (i summarize the main approaches developed until now for the photodynamic inactivation of bacteriophages and mammalian viruses and, (ii discuss and compare the present state of the art of mammalian viruses PDI with phage photoinactivation, with special focus on the most relevant mechanisms, molecular targets and factors affecting the viral inactivation process.

  1. Optimization and Characterization of Candidate Strain for Coxsackievirus A16 Inactivated Vaccine

    Directory of Open Access Journals (Sweden)

    Jingliang Li

    2015-07-01

    Full Text Available Coxsackievirus A16 (CA16 and enterovirus 71 (EV71, both of which can cause hand, foot and mouth disease (HFMD, are responsible for large epidemics in Asian and Pacific areas. Although inactivated EV71 vaccines have completed testing in phase III clinical trials in Mainland China, CA16 vaccines are still under development. A Vero cell-based inactivated CA16 vaccine was developed by our group. Screening identified a CA16 vaccine strain (CC024 isolated from HFMD patients, which had broad cross-protective abilities and satisfied all requirements for vaccine production. Identification of the biological characteristics showed that the CA16CC024 strain had the highest titer (107.5 CCID50/mL in Vero cells, which would benefit the development of an EV71/CA16 divalent vaccine. A potential vaccine manufacturing process was established, including the selection of optimal time for virus harvesting, membrane for diafiltration and concentration, gel-filtration chromatography for the down-stream virus purification and virus inactivation method. Altogether, the analyses suggested that the CC-16, a limiting dilution clone of the CC024 strain, with good genetic stability, high titer and broad-spectrum immunogenicity, would be the best candidate strain for a CA16 inactivated vaccine. Therefore, our study provides valuable information for the development of a Vero cell-based CA16 or EV71-CA16 divalent inactivated vaccine.

  2. 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.

  3. [Inactivated poliovirus vaccines: an inevitable choice for eliminating poliomyelitis].

    Science.gov (United States)

    Vidor, J D; Jean-Denis, Shu

    2016-12-06

    The inactivated poliovirus vaccine (IPV) is a very old tool in the fight against poliomyelitis. Though supplanted by oral poliovirus vaccine (OPV) in the 1960s and 1970s, the IPV has now become an inevitable choice because of the increasingly recognized risks associated with continuous use of OPVs. Following the pioneering work of Jonas Salk, who established key principles for the IPV, considerable experience has accumulated over the years. This work has led to modern Salk IPV-containing vaccines, based on the use of inactivated wildtype polioviruses, which have been deployed for routine use in many countries. Very good protection against paralysis is achieved with IPV through the presence of circulating antibodies able to neutralize virus infectivity toward motor neurons. In addition, with IPV, a variable degree of protection against mucosal infection (and therefore transmission) through mucosal antibodies and immune cells is achieved, depending on previous exposure of subjects to wildtype or vaccine polioviruses. The use of an IPV-followed-by-OPV sequential immunization schedule has the potential advantage of eliminating the vaccine-associated paralytic poliomyelitis (VAPP) risk, while limiting the risks of vaccine-derived poliovirus (VDPVs). Sabin strain-derived IPVs are new tools, only recently beginning to be deployed, and data are being generated to document their performance. IPVs will play an irreplaceable role in global eradication of polio.

  4. 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.

  5. Inactivated Recombinant Rabies Viruses Displaying Canine Distemper Virus Glycoproteins Induce Protective Immunity against Both Pathogens.

    Science.gov (United States)

    da Fontoura Budaszewski, Renata; Hudacek, Andrew; Sawatsky, Bevan; Krämer, Beate; Yin, Xiangping; Schnell, Matthias J; von Messling, Veronika

    2017-04-15

    The development of multivalent vaccines is an attractive methodology for the simultaneous prevention of several infectious diseases in vulnerable populations. Both canine distemper virus (CDV) and rabies virus (RABV) cause lethal disease in wild and domestic carnivores. While RABV vaccines are inactivated, the live-attenuated CDV vaccines retain residual virulence for highly susceptible wildlife species. In this study, we developed recombinant bivalent vaccine candidates based on recombinant vaccine strain rabies virus particles, which concurrently display the protective CDV and RABV glycoprotein antigens. The recombinant viruses replicated to near-wild-type titers, and the heterologous glycoproteins were efficiently expressed and incorporated in the viral particles. Immunization of ferrets with beta-propiolactone-inactivated recombinant virus particles elicited protective RABV antibody titers, and animals immunized with a combination of CDV attachment protein- and fusion protein-expressing recombinant viruses were protected from lethal CDV challenge. However, animals that were immunized with only a RABV expressing the attachment protein of CDV vaccine strain Onderstepoort succumbed to infection with a more recent wild-type strain, indicating that immune responses to the more conserved fusion protein contribute to protection against heterologous CDV strains. IMPORTANCE Rabies virus and canine distemper virus (CDV) cause high mortality rates and death in many carnivores. While rabies vaccines are inactivated and thus have an excellent safety profile and high stability, live-attenuated CDV vaccines can retain residual virulence in highly susceptible species. Here we generated recombinant inactivated rabies viruses that carry one of the CDV glycoproteins on their surface. Ferrets immunized twice with a mix of recombinant rabies viruses carrying the CDV fusion and attachment glycoproteins were protected from lethal CDV challenge, whereas all animals that received

  6. 75 FR 6211 - Prospective Grant of Exclusive License: Purified Inactivated Dengue Tetravalent Vaccine...

    Science.gov (United States)

    2010-02-08

    ... Exclusive License: Purified Inactivated Dengue Tetravalent Vaccine Containing a Common 30 Nucleotide Deletion in the 3'-UTR of Dengue Types 1,2,3, and 4 AGENCY: National Institutes of Health, Public Health...., ``Development of Mutations Useful for Attenuating Dengue Viruses and Chimeric Dengue Viruses''-- European Patent...

  7. The field effectiveness of routine and emergency vaccination with an inactivated vaccine against foot and mouth disease.

    Science.gov (United States)

    Elnekave, E; Li, Y; Zamir, L; Even-Tov, B; Hamblin, P; Gelman, B; Hammond, J; Klement, E

    2013-01-30

    High potency, inactivated foot and mouth disease (FMD) vaccines may be used in non endemic countries for emergency vaccination during outbreaks in order to prevent virus spread. In endemic countries either standard or high potency vaccines are used for routine vaccination. Despite their wide use there is a shortage of data on the field effectiveness of inactivated FMD vaccines. Epidemics of FMD caused by viruses of serotype O occur frequently in Israel, where a high potency (≥6PD(50)) vaccine is used for both routine and emergency vaccination. We investigated an outbreak of FMD caused by a virus of serotype O, which took place during 2011 in a feedlot and an adjacent dairy herd. Post outbreak testing of antibodies against non-structural protein demonstrated that infection occurred in 96% of the calves that received two doses of vaccine at least three months prior to the outbreak and more than 50% showed clinical signs consistent with FMD. Replacement heifers that had been vaccinated 3-5 times with the last vaccination administered 7 months prior to the outbreak were all infected and 18% showed clinical signs. Testing of cattle sera of the same vaccination status as the affected cattle demonstrated low neutralizing antibody (NA) titers against the field virus strain and an r(1) value of 0.37 compared to the vaccine strain. In contrast, cattle vaccinated only once but up to two weeks before the outbreak, were almost all protected from clinical disease and to a lesser extent, protected from FMD virus infection, despite low NA titers. We conclude that emergency vaccination was highly effective due to a mechanism not associated with NA, whereas routine vaccination with the same vaccine formulation provided only limited protection due to poor longevity of the elicited immunity and low matching with the field strain (despite an r(1) higher than 0.3). Copyright © 2012 Elsevier Ltd. All rights reserved.

  8. [Immune response to one booster dose of inactivated hepatitis A vaccine in college students].

    Science.gov (United States)

    Liao, Z; Feng, X W; Liu, X E; Zhou, Y S; Wen, H R; Peng, S H; Zhang, Y X; Xu, B; Zhuang, H; Chen, H Y

    2017-05-10

    Objective: To evaluate the safety and immunogenicity of one booster dose of inactivated hepatitis A vaccine in young adults. Methods: The subjects were selected from participants in the clinical trial of immunogenicity of inactivated and attenuated live hepatitis A vaccine in young adults. Eligible subjects were those who had received one dose of inactivated or attenuated hepatitis A vaccine, could be contacted and were sero-negative before primary vaccination. All qualified subjects were immunized with one booster dose of inactivated hepatitis A vaccine. The blood samples were collected before booster dose vaccination and 28 days after the immunization. Anti-HAV antibody titer ≥20 mIU/ml was considered to be sero-protected against hepatitis A virus. Results: The GMCs in the inactivated HAV vaccine group and attenuated live vaccine group before booster dose vaccination were 70.80 mIU/ml and 50.12 mIU/ml, respectively, and the sero-protection rates were 94.7 % and 65.0 % , respectively. After the vaccination of the booster dose, the sero-protection rates in both groups were 100.0 % , and the GMCs were 2 816.09 mIU/ml and 2 654.55 mIU/ml, respectively. Conclusion: The GMCs and sero-protection rates of anti-HAV antibody in young adults declined after three years of the primary vaccination. However, the higher GMC and sero-protection rate were observed in the inactivated vaccine group than in the attenuated live vaccine group. Significant increases of GMC levels were observed in both groups after one booster dose vaccination.

  9. 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...

  10. 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...

  11. 1,5 iodonaphthyl Azide Inactivated V3526 Protects against Aerosol Challenge with Virulent Venezuelan Equine Encephalitis Virus.

    Science.gov (United States)

    2016-06-02

    1 1,5 iodonaphthyl Azide -Inactivated V3526 Protects against Aerosol Challenge with Virulent Venezuelan Equine Encephalitis Virus. Paridhi...immunogenic and does not protect against an aerosol challenge with virulent VEEV. We have previously shown that VEEV inactivated by 1,5 iodonaphthy azide ...of immunization provided maximum amount of protection. Key words: Venezuelan equine encephalitis, vaccine, inactivated, iodonaphthyl azide

  12. An inactivated cell-culture vaccine against yellow fever.

    Science.gov (United States)

    Monath, Thomas P; Fowler, Elizabeth; Johnson, Casey T; Balser, John; Morin, Merribeth J; Sisti, Maggie; Trent, Dennis W

    2011-04-07

    Yellow fever is a lethal viral hemorrhagic fever occurring in Africa and South America. A highly effective live vaccine (17D) is widely used for travelers to and residents of areas in which yellow fever is endemic, but the vaccine can cause serious adverse events, including viscerotropic disease, which is associated with a high rate of death. A safer, nonreplicating vaccine is needed. In a double-blind, placebo-controlled, dose-escalation, phase 1 study of 60 healthy subjects between 18 and 49 years of age, we investigated the safety and immunogenicity of XRX-001 purified whole-virus, β-propiolactone-inactivated yellow fever vaccine produced in Vero cell cultures and adsorbed to aluminum hydroxide (alum) adjuvant. On two visits 21 days apart, subjects received intramuscular injections of vaccine that contained 0.48 μg or 4.8 μg of antigen. Levels of neutralizing antibodies were measured at baseline and on days 21, 31, and 42. The vaccine induced the development of neutralizing antibodies in 100% of subjects receiving 4.8 μg of antigen in each injection and in 88% of subjects receiving 0.48 μg of antigen in each injection. Antibody levels increased by day 10 after the second injection, at which time levels were significantly higher with the 4.8-μg formulation than with the 0.48-μg formulation (geometric mean titer, 146 vs. 39; P<0.001). Three adverse events occurred at a higher incidence in the two vaccine groups than in the placebo group: mild pain, tenderness, and (much less frequently) itching at the injection site. One case of urticaria was observed on day 3 after the second dose of 4.8 μg of vaccine. A two-dose regimen of the XRX-001 vaccine, containing inactivated yellow fever antigen with an alum adjuvant, induced neutralizing antibodies in a high percentage of subjects. XRX-001 has the potential to be a safer alternative to live attenuated 17D vaccine. (Funded by Xcellerex; ClinicalTrials.gov number, NCT00995865.).

  13. Antibody response in cattle after vaccination with inactivated and attenuated rabies vaccines

    Directory of Open Access Journals (Sweden)

    RODRIGUES da SILVA Andréa de Cássia

    2000-01-01

    Full Text Available Despite the absence of current official reports showing the number of cattle infected by rabies, it is estimated that nearly 30,000 bovines are lost each year in Brazil. In order to minimize the important economic losses, control of the disease is achieved by eliminating bat colonies and by herd vaccination. In this study, we compare the antibody response in cattle elicited by vaccination with an attenuated ERA vaccine (AEvac and an inactivated-adjuvanted PV (IPVvac vaccine. The antibody titers were appraised by cell-culture neutralization test and ELISA, and the percentage of seropositivity was ascertained for a period of 180 days. IPVvac elicited complete seropositivity rates from day 30 to day 150, and even on day 180, 87% of the sera showed virus-neutralizing antibody titers (VNA higher than 0.5IU/ml. There were no significant differences between the VNA titers and seropositivity rates obtained with IPVvac in the two methods tested. AEvac, however, elicited significantly lower titers than those observed in the group receiving inactivated vaccine. In addition, the profiles of antirabies IgG antibodies, evaluated by ELISA, and VNA, appraised by cell-culture neutralization test, were slightly different, when both vaccines were compared.

  14. In vitro neutralization against HoBi-like viruses by antiobodies in serum of cattle immunized with inactivated or modified live vaccines of bovine viral diarrhea virus 1 and 2

    Science.gov (United States)

    HoBi-like viruses are an emerging species of pestiviruses with genetic and antigenic similarities to bovine viral diarrhea viruses 1 and 2 (BVDV1 and BVDV2). These viruses have been detected associated with respiratory and/or reproductive disease in cattle in Italy and Brazil. Vaccines for HoBi-like...

  15. Preparation of FMD type A87/IRN inactivated vaccine by gamma irradiation and the immune response on guinea pig

    International Nuclear Information System (INIS)

    Sedeh, Farahnaz Motamedi; Shafaee, Kamal; Fatolahi, Hadi; Arbabi, Kourosh; Khorasani, Akbar

    2008-01-01

    FMD is one of the most economically damaging diseases that affect livestock animals. In this study FMD Virus type A87/IRN was multiplied on BHK21 cells. The virus was titrated by TCID50 method, it was 10 7.5 /ml. The FMD virus samples were inactivated by gamma ray from 60 Co source at -20 deg C. Safety test was done by IBRS2 monolayer cell culture method, also antigenicity of irradiated and un-irradiated virus samples were studied by Complement Fixation Test. The dose/survival curve for irradiated FMD Virus was drawn, the optimum dose range for inactivation of FMDV type A87/IRN and unaltered antigenicity was obtained 40-44 kGy. The inactivated virus samples by irradiation and ethyleneimine (EI) were formulated respectively as vaccine with Al(OH) 3 gel and other substances. The vaccines were inoculated to Guinea pigs and the results of Serum Neutralization Test for the normal vaccine and radio-vaccine showed protective titer after 8 months. The potency test of the inactivated vaccines was done, PD50 Value of the vaccines were calculated 7.06 and 5.6 for inactivated vaccine by EI and gamma irradiation respectively. (author)

  16. 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

  17. 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,

  18. Inactivated recombinant plant virus protects dogs from a lethal challenge with canine parvovirus

    DEFF Research Database (Denmark)

    Langeveld, J.P.M.; Brennan, F.R.; Martinez-Torrecuadrada, J.L.

    2001-01-01

    A vaccine based upon a recombinant plant virus (CPMV-PARVO1), displaying a peptide derived from the VP2 capsid protein of canine parvovirus (CPV), has previously been described. To date, studies with the vaccine have utilized viable plant chimaeric particles (CVPs). In this study, CPMV-PARVO1...... was inactivated by UV treatment to remove the possibility of replication of the recombinant plant virus in a plant host after manufacture of the vaccine. We show that the inactivated CVP is able to protect dogs from a lethal challenge with CPV following parenteral immunization with the vaccine. Dogs immunized...... were comparable to those seen in dogs immunized with the same VP2-peptide coupled to keyhole limpet hemocyanin (KLH). Since plant virus-derived vaccines have the potential for cost-effective manufacture and are not known to replicate in mammalian cells, they represent a viable alternative to cut...

  19. Preclinical Development of Inactivated Rabies Virus–Based Polyvalent Vaccine Against Rabies and Filoviruses

    Science.gov (United States)

    Willet, Mallory; Kurup, Drishya; Papaneri, Amy; Wirblich, Christoph; Hooper, Jay W.; Kwilas, Steve A.; Keshwara, Rohan; Hudacek, Andrew; Beilfuss, Stefanie; Rudolph, Grit; Pommerening, Elke; Vos, Adriaan; Neubert, Andreas; Jahrling, Peter; Blaney, Joseph E.; Johnson, Reed F.; Schnell, Matthias J.

    2015-01-01

    We previously described the generation of a novel Ebola virus (EBOV) vaccine based on inactivated rabies virus (RABV) containing EBOV glycoprotein (GP) incorporated in the RABV virion. Our results demonstrated safety, immunogenicity, and protective efficacy in mice and nonhuman primates (NHPs). Protection against viral challenge depended largely on the quality of the humoral immune response against EBOV GP. Here we present the extension and improvement of this vaccine by increasing the amount of GP incorporation into virions via GP codon-optimization as well as the addition of Sudan virus (SUDV) and Marburg virus (MARV) GP containing virions. Immunogenicity studies in mice indicate similar immune responses for both SUDV GP and MARV GP compared to EBOV GP. Immunizing mice with multiple antigens resulted in immune responses similar to immunization with a single antigen. Moreover, immunization of NHP with the new inactivated RABV EBOV vaccine resulted in high titer neutralizing antibody levels and 100% protection against lethal EBOV challenge when applied with adjuvant. Our results indicate that an inactivated polyvalent vaccine against RABV filoviruses is achievable. Finally, the novel vaccines are produced on approved VERO cells and a clinical grade RABV/EBOV vaccine for human trials has been produced. PMID:26063224

  20. 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...

  1. Novel vaccines against influenza viruses

    OpenAIRE

    Kang, Sang-Moo; Song, Jae-Min; Compans, Richard W.

    2011-01-01

    Killed and live attenuated influenza virus vaccines are effective in preventing and curbing the spread of influenza epidemics when the strains present in the vaccines are closely matched with the predicted epidemic strains. These vaccines are primarily targeted to induce immunity to the variable major target antigen, hemagglutinin (HA) of influenza virus. However, current vaccines are not effective in preventing the emergence of new pandemic or highly virulent viruses. New approaches are bein...

  2. Vaccination against acute respiratory virus infections and measles in man.

    NARCIS (Netherlands)

    A.D.M.E. Osterhaus (Albert); P. de Vries (Petra)

    1992-01-01

    textabstractSeveral viruses may cause more or less severe acute respiratory infections in man, some of which are followed by systemic infection. Only for influenza and measles are licensed vaccines available at present. The protection induced by influenza vaccines, which are based on inactivated

  3. Efficacy trial of heat-inactivated hepatitis B vaccine (CLB) in male homosexuals in the Netherlands

    NARCIS (Netherlands)

    Coutinho, R. A.; Lelie, P. N.; Albrecht-van Lent, P.; Stoutjesdijk, L.; Huisman, J.; Kuipers, H.; Schut, L. J.; Reerink-Brongers, E. E.; Reesink, H. W.; van Aken, W. G.

    1983-01-01

    The efficacy of a heat-inactivated hepatitis B virus (HBV) vaccine, containing 3 micrograms-HBsAg, was studied among a group of 800 susceptible homosexual men. The trial was conducted randomized, placebo-controlled and double blind. At the trial end point (21.5 months) the attack-rate for all HBV

  4. Randomized Trials Comparing Inactivated Vaccine after Medium- or High-titer Measles Vaccine with Standard Titer Measles Vaccine after Inactivated Vaccine

    DEFF Research Database (Denmark)

    Aaby, Peter; Ravn, Henrik; Benn, Christine S.

    2016-01-01

    Background: Observational studies have suggested that girls have higher mortality if their most recent immunization is an inactivated vaccine rather than a live vaccine. We therefore reanalyzed 5 randomized trials of early measles vaccine (MV) in which it was possible to compare an inactivated......) compared with a standard titer MV (after inactivated vaccine). Girls had a MRR of 1.89 (1.27-2.80), whereas there was no effect for boys, the sex-differential effect being significant (P = 0.02). Excluding measles cases did not alter these conclusions, the MRR after inactivated vaccines (after MTMV or HTMV......) being 1.40 (1.06-1.86) higher overall and 1.92 (1.29-2.86) for girls. Control for variations in national immunization schedules for other vaccines did not modify these results. Conclusions: After 9 months of age, all children had been immunized against measles, and mortality in girls was higher when...

  5. A single center, open label study of intradermal administration of an inactivated purified chick embryo cell culture rabies virus vaccine in adults.

    Science.gov (United States)

    Recuenco, Sergio; Warnock, Eli; Osinubi, Modupe O V; Rupprecht, Charles E

    2017-08-03

    In the USA, rabies vaccines (RVs) are licensed for intramuscular (IM) use only, although RVs are licensed for use by the intradermal (ID) route in many other countries. Recent limitations in supplies of RV in the USA reopened discussions on the more efficient use of available biologics, including utilization of more stringent risk assessments, and potential ID RV administration. A clinical trial was designed to compare the immunogenic and adverse effects of a purified chicken embryo cell (PCEC) RV administered ID or IM. Enrollment was designed in four arms, ID Pre-Exposure Prophylaxis (Pre-EP), IM Pre-EP, ID Booster, and IM Booster vaccination. Enrollment included 130 adult volunteers. The arms with IM administration received vaccine according to the current ACIP recommendations: Pre-EP, three 1mL (2.5 I.U.) RV doses, each on day 0, 7, and 21; or a routine Booster, one 1ml dose. The ID groups received the same schedule, but doses administered were in a volume of 0.1mL (0.25 I.U.). The rate of increase in rabies virus neutralizing antibody titers 14-21days after vaccination were similar in the ID and correspondent IM groups. The GMT values for ID vaccination were slightly lower than those for IM vaccination, for both naïve and booster groups, and these differences were statistically significant by t-test. Fourteen days after completing vaccination, all individuals developed RV neutralizing antibody titers over the minimum arbitrary value obtained with the rapid fluorescent focus inhibition test (RFFIT). Antibodies were over the set threshold until the end of the trial, 160days after completed vaccination. No serious adverse reactions were reported. Most frequent adverse reactions were erythema, induration and tenderness, localized at the site of injection. Multi use of 1mL rabies vaccine vials for ID doses of 0.1 was demonstrated to be both safe and inmunogenic. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. 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...

  7. Need for a safe vaccine against respiratory syncytial virus infection

    Directory of Open Access Journals (Sweden)

    Joo-Young Kim

    2012-09-01

    Full Text Available Human respiratory syncytial virus (HRSV is a major cause of severe respiratory tract illnesses in infants and young children worldwide. Despite its importance as a respiratory pathogen, there is currently no licensed vaccine for HRSV. Following failure of the initial trial of formalin-inactivated virus particle vaccine, continuous efforts have been made for the development of safe and efficacious vaccines against HRSV. However, several obstacles persist that delay the development of HRSV vaccine, such as the immature immune system of newborn infants and the possible Th2-biased immune responses leading to subsequent vaccine-enhanced diseases. Many HRSV vaccine strategies are currently being developed and evaluated, including live-attenuated viruses, subunit-based, and vector-based candidates. In this review, the current HRSV vaccines are overviewed and the safety issues regarding asthma and vaccine-induced pathology are discussed.

  8. 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.

  9. 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...

  10. Porinas as an adyuvant of inactivated Newcastle vaccine in broilers

    Directory of Open Access Journals (Sweden)

    Francisco Bustos M.

    2005-05-01

    Full Text Available Three groups of 25 broilers were vaccinated on two opportunities by aerosol using inactivated NC (Newcastle virus and different helper concentrations of porinas (20 ìg, 50 ìg, 125 ìg. A fourth group was injected with live B1 virus (12 and 28 days of age nasally. The NC inactivated virus (La Sota strain was concentrated 10 times with PEG with a final titer of 1:2.056. Twenty serums for each group were taken in order to evaluate NC antibodies using the HI and double immuno-difusion tests for IgA detection at 1, 12, 28 and 42 days of age. During the study the chickens were on a restricted diet in order to control ascites (2.640 mosl. On day 42, two broilers of the fourth group (live virus presented ascites and 1 broiler of group 1 presented lung edema (20 ìg. The geometric mean for NC antibodies titers at 42 days of age was 2 in the groups 1,2,3 and 5.7 in the group 4 (Log 2. For IgA, 180 mg/dl, 135 mg/dl, 120 mg/dl and 176 mg/dl respectively. Three broilers of each group were challenged with a pathogenic strain of NC, at 42 day of age, without signs of disease after 72 hours when the positive control group was dead. Gross and microscopic lesions were not detected in the bursa of Fabricius or thymo. [thymo sounds like short hand for something that should be properly named.] Very good animal weight, conversion and efficiency results were observed in all the groups. New studies using a fixed dose of porinas, larger numbers of broilers and the establishment of protective levels of IgA against NC challenge are recommended.

  11. Novel vaccines against influenza viruses.

    Science.gov (United States)

    Kang, S M; Song, J M; Compans, R W

    2011-12-01

    Killed and live attenuated influenza virus vaccines are effective in preventing and curbing the spread of influenza epidemics when the strains present in the vaccines are closely matched with the predicted epidemic strains. These vaccines are primarily targeted to induce immunity to the variable major target antigen, hemagglutinin (HA) of influenza virus. However, current vaccines are not effective in preventing the emergence of new pandemic or highly virulent viruses. New approaches are being investigated to develop universal influenza virus vaccines as well as to apply more effective vaccine delivery methods. Conserved vaccine targets including the influenza M2 ion channel protein and HA stalk domains are being developed using recombinant technologies to improve the level of cross protection. In addition, recent studies provide evidence that vaccine supplements can provide avenues to further improve current vaccies. Copyright © 2011 Elsevier B.V. All rights reserved.

  12. Gamma ray inactivation of some animal viruses.

    Science.gov (United States)

    Thomas, F C; Davies, A G; Dulac, G C; Willis, N G; Papp-Vid, G; Girard, A

    1981-10-01

    Twenty samples of animal viruses comprising 14 different viruses in 12 families were subjected to varying doses of gamma irradiation from a 60Co source in a Gamma Cell 220 (Atomic Energy of Canada Limited) to determine lethal dose levels. The dose responses appeared linear throughout inactivation. The D10 values, that is the dose necessary to reduce infectivity by one log10, ranged from less than 0.20 Megarads to approximately 0.55 Megarads. There was not a complete inverse correlation between the target size (virion core) and the D10 value.

  13. Gamma ray inactivation of some animal viruses.

    OpenAIRE

    Thomas, F C; Davies, A G; Dulac, G C; Willis, N G; Papp-Vid, G; Girard, A

    1981-01-01

    Twenty samples of animal viruses comprising 14 different viruses in 12 families were subjected to varying doses of gamma irradiation from a 60Co source in a Gamma Cell 220 (Atomic Energy of Canada Limited) to determine lethal dose levels. The dose responses appeared linear throughout inactivation. The D10 values, that is the dose necessary to reduce infectivity by one log10, ranged from less than 0.20 Megarads to approximately 0.55 Megarads. There was not a complete inverse correlation betwee...

  14. 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.

  15. Impact of universal mass vaccination with monovalent inactivated hepatitis A vaccines – A systematic review

    Science.gov (United States)

    Stuurman, Anke L.; Marano, Cinzia; Bunge, Eveline M.; De Moerlooze, Laurence; Shouval, Daniel

    2017-01-01

    ABSTRACT The WHO recommends integration of universal mass vaccination (UMV) against hepatitis A virus (HAV) in national immunization schedules for children aged ≥1 year, if justified on the basis of acute HAV incidence, declining endemicity from high to intermediate and cost-effectiveness. This recommendation has been implemented in several countries. Our aim was to assess the impact of UMV using monovalent inactivated hepatitis A vaccines on incidence and persistence of anti-HAV (IgG) antibodies in pediatric populations. We conducted a systematic review of literature published between 2000 and 2015 in PubMed, Cochrane Library, LILACS, IBECS identifying a total of 27 studies (Argentina, Belgium, China, Greece, Israel, Panama, the United States and Uruguay). All except one study showed a marked decline in the incidence of hepatitis A post introduction of UMV. The incidence in non-vaccinated age groups decreased as well, suggesting herd immunity but also rising susceptibility. Long-term anti-HAV antibody persistence was documented up to 17 y after a 2-dose primary vaccination. In conclusion, introduction of UMV in countries with intermediate endemicity for HAV infection led to a considerable decrease in the incidence of hepatitis A in vaccinated and in non-vaccinated age groups alike. PMID:27786671

  16. Impact of universal mass vaccination with monovalent inactivated hepatitis A vaccines - A systematic review.

    Science.gov (United States)

    Stuurman, Anke L; Marano, Cinzia; Bunge, Eveline M; De Moerlooze, Laurence; Shouval, Daniel

    2017-03-04

    The WHO recommends integration of universal mass vaccination (UMV) against hepatitis A virus (HAV) in national immunization schedules for children aged ≥1 year, if justified on the basis of acute HAV incidence, declining endemicity from high to intermediate and cost-effectiveness. This recommendation has been implemented in several countries. Our aim was to assess the impact of UMV using monovalent inactivated hepatitis A vaccines on incidence and persistence of anti-HAV (IgG) antibodies in pediatric populations. We conducted a systematic review of literature published between 2000 and 2015 in PubMed, Cochrane Library, LILACS, IBECS identifying a total of 27 studies (Argentina, Belgium, China, Greece, Israel, Panama, the United States and Uruguay). All except one study showed a marked decline in the incidence of hepatitis A post introduction of UMV. The incidence in non-vaccinated age groups decreased as well, suggesting herd immunity but also rising susceptibility. Long-term anti-HAV antibody persistence was documented up to 17 y after a 2-dose primary vaccination. In conclusion, introduction of UMV in countries with intermediate endemicity for HAV infection led to a considerable decrease in the incidence of hepatitis A in vaccinated and in non-vaccinated age groups alike.

  17. Equine abortion (herpes) virus: strain differences in susceptibility to inactivation by dithiothreitol.

    Science.gov (United States)

    Klingeborn, B; Dinter, Z

    1972-06-01

    The infectivity of equine abortion (herpes) virus (EAV) was inactivated by treatment with reduced dithiothreitol (DTT). According to their susceptibility to DTT, the EAV strains could be divided into three groups. The vaccine strain RAC-H (419) proved to be more resistant to DTT than all of the other 14 strains tested. The hemagglutinin of EAV was also inactivated by DTT; no strain differences were observed in this respect.

  18. Ebola Virus Inactivation by Detergents Is Annulled in Serum

    NARCIS (Netherlands)

    van Kampen, Jeroen J. A.; Tintu, Andrei; Russcher, Henk; Fraaij, Pieter L. A.; Reusken, Chantal B. E. M.; Rijken, Mikel; van Hellemond, Jaap J.; van Genderen, Perry J. J.; Koelewijn, Rob; de Jong, Menno D.; Haddock, Elaine; Fischer, Robert J.; Munster, Vincent J.; Koopmans, Marion P. G.

    2017-01-01

    Treatment of blood samples from hemorrhagic fever virus (HFV)-infected patients with 0.1% detergents has been recommended for virus inactivation and subsequent safe laboratory testing. However, data on virus inactivation by this procedure are lacking. Here we show the effect of this procedure on

  19. 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.

  20. 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

  1. 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.

  2. Examination of virus shedding in semen from vaccinated and from previously infected boars after experimental challenge with porcine reproductive and respiratory syndrome virus

    DEFF Research Database (Denmark)

    Nielsen, Thomas L.; Nielsen, Jens; Have, Per

    1997-01-01

    to the Danish pig industry. The use of a vaccination-program may be a way to avoid or reduce the problem, This study evaluates the use of two vaccines: One live, attenuated vaccine and one inactivated vaccine, A pronounced reduction in viremia and shedding of virus in semen was demonstrated by use of the live...... vaccine compared to the non-vaccinated control animals. In contrast, no changes in onset, level and duration of viremia and shedding of virus in semen were observed using the inactivated vaccine, Neither viremia nor seminal shedding of virus was detected in previously PRRSV-infected, PRRSV...

  3. 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.

  4. Feline immunodeficiency virus (FIV) vaccine efficacy and FIV neutralizing antibodies.

    Science.gov (United States)

    Coleman, James K; Pu, Ruiyu; Martin, Marcus M; Noon-Song, Ezra N; Zwijnenberg, Raphael; Yamamoto, Janet K

    2014-02-03

    A HIV-1 tier system has been developed to categorize the various subtype viruses based on their sensitivity to vaccine-induced neutralizing antibodies (NAbs): tier 1 with greatest sensitivity, tier 2 being moderately sensitive, and tier 3 being the least sensitive to NAbs (Mascola et al., J Virol 2005; 79:10103-7). Here, we define an FIV tier system using two related FIV dual-subtype (A+D) vaccines: the commercially available inactivated infected-cell vaccine (Fel-O-Vax(®) FIV) and its prototype vaccine solely composed of inactivated whole viruses. Both vaccines afforded combined protection rates of 100% against subtype-A tier-1 FIVPet, 89% against subtype-B tier-3 FIVFC1, 61% against recombinant subtype-A/B tier-2 FIVBang, 62% against recombinant subtype-F'/C tier-3 FIVNZ1, and 40% against subtype-A tier-2 FIVUK8 in short-duration (37-41 weeks) studies. In long-duration (76-80 weeks) studies, the commercial vaccine afforded a combined protection rate of at least 46% against the tier-2 and tier-3 viruses. Notably, protection rates observed here are far better than recently reported HIV-1 vaccine trials (Sanou et al., The Open AIDS J 2012; 6:246-60). Prototype vaccine protection against two tier-3 and one tier-2 viruses was more effective than commercial vaccine. Such protection did not correlate with the presence of vaccine-induced NAbs to challenge viruses. This is the first large-scale (228 laboratory cats) study characterizing short- and long-duration efficacies of dual-subtype FIV vaccines against heterologous subtype and recombinant viruses, as well as FIV tiers based on in vitro NAb analysis and in vivo passive-transfer studies. These studies demonstrate that not all vaccine protection is mediated by vaccine-induced NAbs. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Antibody response of five bird species after vaccination with a killed West Nile virus vaccine.

    Science.gov (United States)

    Okeson, Danelle M; Llizo, Shirley Yeo; Miller, Christine L; Glaser, Amy L

    2007-06-01

    West Nile virus has been associated with numerous bird mortalities in the United States since 1999. Five avian species at three zoological parks were selected to assess the antibody response to vaccination for West Nile virus: black-footed penguins (Spheniscus demersus), little blue penguins (Eudyptula minor), American flamingos (Phoenicopterus ruber), Chilean flamingos (Phoenicopterus chilensis), and Attwater's prairie chickens (Tympanuchus cupido attwateri). All birds were vaccinated intramuscularly at least twice with a commercially available inactivated whole virus vaccine (Innovator). Significant differences in antibody titer over time were detected for black-footed penguins and both flamingo species.

  6. Antigenic characterization of a formalin-inactivated poliovirus vaccine derived from live-attenuated Sabin strains.

    Science.gov (United States)

    Tano, Yoshio; Shimizu, Hiroyuki; Martin, Javier; Nishimura, Yorihiro; Simizu, Bunsiti; Miyamura, Tatsuo

    2007-10-10

    A candidate inactivated poliovirus vaccine derived from live-attenuated Sabin strains (sIPV), which are used in the oral poliovirus vaccine (OPV), was prepared in a large-production scale. The modification of viral antigenic epitopes during the formalin inactivation process was investigated by capture ELISA assays using type-specific and antigenic site-specific monoclonal antibodies (MoAbs). The major antigenic site 1 was modified during the formalin inactivation of Sabin 1. Antigenic sites 1-3 were slightly modified during the formalin inactivation of Sabin 2 strain. Sites 1 and 3 were altered on inactivated Sabin 3 virus. These alterations were different to those shown by wild-type Saukett strain, used in conventional IPV (cIPV). It has been previously reported that type 1 sIPV showed higher immunogenicity to type 1 cIPV whereas types 2 and 3 sIPV induced lower level of immunogenicity than their cIPV counterparts. Our results suggest that the differences in epitope structure after formalin inactivation may account, at least in part, for the observed differences in immunogenicity between Sabin and wild-type inactivated poliovaccines.

  7. Effect of pre-existing anti-tick-borne encephalitis virus immunity on neutralising antibody response to the Vero cell-derived, inactivated Japanese encephalitis virus vaccine candidate IC51.

    Science.gov (United States)

    Schuller, Elisabeth; Klade, Christoph S; Heinz, Franz X; Kollaritsch, Herwig; Rendi-Wagner, Pamela; Jilma, Bernd; Tauber, Erich

    2008-11-11

    Japanese encephalitis virus (JEV) is the leading cause of viral encephalitis in Asia with a case fatality rate up to 35% and long-term sequelae up to 75%. This active-controlled, randomized, multi-centre, observer-blind, phase III trial investigated the neutralising antibody response to the new Japanese encephalitis (JE) vaccine IC51 in subjects with (N=81) and without (N=339) pre-existing tick-borne encephalitis (TBE) vaccine induced antibodies as determined by TBE enzyme-linked immunosorbent assay IgG (ELISA). Neutralising antibody response was statistically superior in TBE ELISA-positive subjects compared to TBE ELISA-negative subjects after the first (pvaccination with IC51. Thus, pre-existing vaccine-induced TBE immunity enhances the neutralising JEV-specific antibody response after a single IC51 vaccination.

  8. 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.

  9. Computer Bytes, Viruses and Vaccines.

    Science.gov (United States)

    Palmore, Teddy B.

    1989-01-01

    Presents a history of computer viruses, explains various types of viruses and how they affect software or computer operating systems, and describes examples of specific viruses. Available vaccines are explained, and precautions for protecting programs and disks are given. (nine references) (LRW)

  10. New vaccines against influenza virus

    Science.gov (United States)

    Lee, Young-Tae; Kim, Ki-Hye; Ko, Eun-Ju; Lee, Yu-Na; Kim, Min-Chul; Kwon, Young-Man; Tang, Yinghua; Cho, Min-Kyoung; Lee, Youn-Jeong

    2014-01-01

    Vaccination is one of the most effective and cost-benefit interventions that prevent the mortality and reduce morbidity from infectious pathogens. However, the licensed influenza vaccine induces strain-specific immunity and must be updated annually based on predicted strains that will circulate in the upcoming season. Influenza virus still causes significant health problems worldwide due to the low vaccine efficacy from unexpected outbreaks of next epidemic strains or the emergence of pandemic viruses. Current influenza vaccines are based on immunity to the hemagglutinin antigen that is highly variable among different influenza viruses circulating in humans and animals. Several scientific advances have been endeavored to develop universal vaccines that will induce broad protection. Universal vaccines have been focused on regions of viral proteins that are highly conserved across different virus subtypes. The strategies of universal vaccines include the matrix 2 protein, the hemagglutinin HA2 stalk domain, and T cell-based multivalent antigens. Supplemented and/or adjuvanted vaccination in combination with universal target antigenic vaccines would have much promise. This review summarizes encouraging scientific advances in the field with a focus on novel vaccine designs. PMID:24427759

  11. 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.

  12. 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.

  13. 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...

  14. Inactivation of Aujeszky's disease virus in slurry at various temperatures

    DEFF Research Database (Denmark)

    Bøtner, Anette

    1991-01-01

    Survival of Aujeszky's disease virus in pig slurry was investigated during anaerobic storage at 5, 20, 35, 40, 45, 50 and 55°C using 100-ml laboratory models simulating the conditions in slurry tanks during winter and summer seasons and during anaerobic digestion in batch reactors. The inactivation...... rate was found to increase with increasing temperature. Virus was inactivated at 5 and 20°C in 15 weeks and 2 weeks, respectively. At 35°C (mesophilic conditions) the virus was inactivated in 5 hours and at 55°C (thermophilic conditions) no virus could be detected after 10 minutes....

  15. 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...

  16. Zika virus-like particle (VLP) based vaccine

    Science.gov (United States)

    Boigard, Hélène; Alimova, Alexandra; Martin, George R.; Katz, Al; Gottlieb, Paul

    2017-01-01

    The newly emerged mosquito-borne Zika virus poses a major public challenge due to its ability to cause significant birth defects and neurological disorders. The impact of sexual transmission is unclear but raises further concerns about virus dissemination. No specific treatment or vaccine is currently available, thus the development of a safe and effective vaccine is paramount. Here we describe a novel strategy to assemble Zika virus-like particles (VLPs) by co-expressing the structural (CprME) and non-structural (NS2B/NS3) proteins, and demonstrate their effectiveness as vaccines. VLPs are produced in a suspension culture of mammalian cells and self-assembled into particles closely resembling Zika viruses as shown by electron microscopy studies. We tested various VLP vaccines and compared them to analogous compositions of an inactivated Zika virus (In-ZIKV) used as a reference. VLP immunizations elicited high titers of antibodies, as did the In-ZIKV controls. However, in mice the VLP vaccine stimulated significantly higher virus neutralizing antibody titers than comparable formulations of the In-ZIKV vaccine. The serum neutralizing activity elicited by the VLP vaccine was enhanced using a higher VLP dose and with the addition of an adjuvant, reaching neutralizing titers greater than those detected in the serum of a patient who recovered from a Zika infection in Brazil in 2015. Discrepancies in neutralization levels between the VLP vaccine and the In-ZIKV suggest that chemical inactivation has deleterious effects on neutralizing epitopes within the E protein. This along with the inability of a VLP vaccine to cause infection makes it a preferable candidate for vaccine development. PMID:28481898

  17. Evaluation of a quadrivalent inactivated vaccine for the protection of cattle against diseases due to common viral infections : research report

    Directory of Open Access Journals (Sweden)

    J.R. Patel

    2004-06-01

    Full Text Available Efficacy of an inactivated quadrivalent vaccine containing infectious bovine rhinotracheitis (IBR virus, parainfluenza type 3 (PI3 virus, bovine virus diarrhoea virus (BVDV and bovine respiratory syncytial virus (BRSV was assessed in naive bovine calves to evaluate short-term (4-18 weeks and long-term (24-38 weeks protection following the basic intramuscular vaccination regime of 2 inoculations a month apart. Vaccination was staggered between the long-term and the short-term groups by about 5 months so that both groups, along with a matched group of 6 unvaccinated (control calves, could be challenged at the same time. Sequential challenges at intervals of 3-8 weeks were done in the order: IBR virus (intranasally, IN, PI3 virus (IN and intratracheally, IT, pestiviruses (IN and BRSV (IN and IT. The IBR virus challenge produced febrile rhinotracheitis (FRT in control calves but both the severity and the duration of FRT was significantly reduced in both vaccinated groups. The amount and the duration of IBR virus shed by the vaccinated groups was significantly reduced compared to the control group. Although PI3 virus, pooled pestivirus and BRSV challenges did not result in a noteworthy disease, challenge virus shedding (amount and duration from the upper (all 3 viruses and the lower (BRSV respiratory tracts was significantly reduced in vaccinated groups. After pestivirus challenge, sera and leukocytes from all control calves were infectious for 6-9 days whereas virus was recovered only from leukocytes in vaccinated calves and only for 1.6-2.7 days. Thus a standard course of the quadrivalent vaccine afforded a significant protection against IBR virus, PI3 virus, BVDV and BRSV for at least 6 months.

  18. [Herpes simplex virus vaccine studies: from past to present].

    Science.gov (United States)

    Us, Dürdal

    2006-10-01

    The dramatical increase in the prevalence of Herpes simplex virus (HSV) infections and the significant physical and psychosocial morbidity of HSV type 2 infections, generate the need for an efficacious HSV vaccine. The most important properties of HSVs that should be targeted for a successful vaccine are neuronal invasion, latency and reactivation in spite of specific host immune responses. The major expectation for an ideal HSV vaccine candidate is to induce sterilizing immunity, which must be effective at all portals of HSV entry; to prevent or reduce the symptomatic disease and to eliminate or at least to limit the asymptomatic viral shedding. The first vaccine studies have began in the 1920s and in the intervening eight decades there have been many attempts to develop an effective one. Although encouraging findings came from experiments in various animal models, human studies have been disappointing, unfortunately. The vaccine strategies that have undergone clinical evaluation until today included autoinoculation of live HSV, whole inactivated vaccines, attenuated live virus vaccines, modified live virus subunit vaccines, cell culture-derived subunit vaccines, recombinant subunit (glycoprotein) vaccines, DISC (Disabled Infectious Single Cycle) virus vaccines, viral vectors and naked DNA vaccines. In most of the clinical studies the failure of HSV vaccines in spite of inducing very high levels of specific neutralizing antibodies have emphasized that cell-mediated immune response, especially Thl type immunity is important in preventing both primary disease and recurrences with HSV, rather than humoral response. The most hopeful result was obtained with HSV-2 gD and alum/MPL vaccine in clinical studies. This vaccine was found 74% effective in preventing genital disease in HSV seronegative women but was not effective in men or seropositive women. In recent years it is possible to genetically engineer HSV to produce a vaccine strain that is protective without

  19. 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.

  20. Efficacy of heat-inactivated hepatitis B vaccine in haemodialysis patients and staff. Double-blind placebo-controlled trial

    NARCIS (Netherlands)

    Desmyter, J.; Colaert, J.; de Groote, G.; Reynders, M.; Reerink-Brongers, E. E.; Lelie, P. N.; Dees, P. J.; Reesink, H. W.

    1983-01-01

    The efficacy of a heat-inactivated hepatitis B vaccine, 3 micrograms of surface antigen (HBsAg), given at 0, 1, 2, and 5 months, was evaluated in 401 haemodialysis patients in 18 centres by a placebo-controlled, double-blind, randomised trial. The attack-rate of hepatitis B virus (HBV) infections in

  1. Anticorpos neutralizantes contra o vírus da Diarréia Viral Bovina (BVDV: comparação entre um imunógeno experimental atenuado e três vacinas comerciais inativadas Vaccination-induced neutralizing antibodies against bovine viral diarrhea virus (BVDV: comparison between an experimental modified-live vaccine and three comercial inactivated vaccines

    Directory of Open Access Journals (Sweden)

    Marcelo de Lima

    2005-02-01

    Full Text Available Os títulos e duração de anticorpos neutralizantes contra o vírus da Diarréia Viral Bovina (BVDV induzidos por uma vacina experimental atenuada (vacina A: dose única foram comparados com os induzidos por três vacinas comerciais inativadas (B, C e D: duas doses com intervalo de 30 dias. Trinta dias após a vacinação (vacina A ou após a segunda dose (vacinas B, C e D, anticorpos neutralizantes contra o BVDV-1 foram detectados em todos os animais (12/12 do grupo A (título médio geométrico GMT=1612,7; em 32 de 36 animais do grupo B (GMT=14,3; 22 de 28 do grupo C (GMT=25,1; e em 16 de 30 do grupo D (GMT=40,0. Anticorpos frente ao BVDV-2 foram detectados em todos os animais do grupo A (GMT=151,0; em 27 de 36 do grupo B (GMT=10,0; 12 de 28 do grupo C (GMT=11,5 e em 10 de 30 animais do grupo D (GMT=10,0. No dia 180 após a vacinação, o número de animais que ainda apresentava anticorpos contra o BVDV-1 e os GMTs para cada grupo foram: vacina A (12/12, GMT=905,0; vacina B (30/36, GMT=28,3; vacina C (20/28, GMT=28,3; vacina D (14/30, GMT=16,1; e contra o BVDV-2 foram: vacina A (12/12, GMT=56,6; vacina B (18/36, GMT=16,8; vacina C (10/28, GMT=21,6 e vacina D (6/30, GMT=16,1. Os títulos médios (GMTs induzidos pela vacina A foram significativamente superiores aos demais, tanto para o BVDV-1 (PThe titers and duration of neutralizing antibodies against bovine viral diarrhea virus (BVDV induced by an experimental attenuated vaccine (vaccine A: one dose were compared to those induced by three commercial inactivated ones (B, C and D: two doses at a 30 day interval. Thirty days after vaccination (vaccine A or the second dose (vaccines B, C and D, neutralizing antibodies to BVDV-1 were detected in all calves (12/12 from group A (mean geometric titer GMT=1612.7; in 32 out of 36 from group B (GMT=14.3; 22/28 from group C (GMT=25.1; 16/30 from group D (GMT=40.0. Antibodies reacting with BVDV-2 were detected in all animals from group A (GMT=151.0; 27

  2. Inactivation of Lassa, Marburg, and Ebola viruses by gamma irradiation

    International Nuclear Information System (INIS)

    Elliott, L.H.; McCormick, J.B.; Johnson, K.M.

    1982-01-01

    Because of the cumbersome conditions experienced in a maximum containment laboratory, methods for inactivating highly pathogenic viruses were investigated. The infectivity of Lassa, Marburg, and Ebola viruses was inactivated without altering the immunological activity after radiation with 60 CO gamma rays. At 4 degrees C, Lassa virus was the most difficult to inactivate with a rate of 5.3 X 10(-6) log 50% tissue culture infective dose per rad of 60 CO radiation, as compared with 6.8 X 10(-6) log 50% tissue culture infective dose per rad for Ebola virus and 8.4 X 10(-6) log 50% tissue culture infective dose per rad for Marburg virus. Experimental inactivation curves, as well as curves giving the total radiation needed to inactivate a given concentration of any of the three viruses, are presented. The authors found this method of inactivation to be superior to UV light or beta-propiolactone inactivation and now routinely use it for preparation of material for protein-chemistry studies or for preparation of immunological reagents

  3. 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

  4. 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 ...

  5. 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...

  6. 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

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

    Science.gov (United States)

    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/ ...

  8. Characterization of a novel oil-in-water emulsion adjuvant for swine influenza virus and Mycoplasma hyopneumoniae vaccines

    Science.gov (United States)

    Vaccines consisting of subunit or inactivated bacteria/virus and potent adjuvants are widely used to control and prevent infectious diseases. Because inactivated and subunit antigens are often less antigenic than live microbes, a growing need exists for the development of new and improved vaccine ad...

  9. Viral Aetiology of Acute Flaccid Paralysis Surveillance Cases, before and after Vaccine Policy Change from Oral Polio Vaccine to Inactivated Polio Vaccine

    Directory of Open Access Journals (Sweden)

    T. S. Saraswathy Subramaniam

    2014-01-01

    Full Text Available Since 1992, surveillance for acute flaccid paralysis (AFP cases was introduced in Malaysia along with the establishment of the National Poliovirus Laboratory at the Institute for Medical Research. In 2008, the Ministry of Health, Malaysia, approved a vaccine policy change from oral polio vaccine to inactivated polio vaccine (IPV. Eight states started using IPV in the Expanded Immunization Programme, followed by the remaining states in January 2010. The objective of this study was to determine the viral aetiology of AFP cases below 15 years of age, before and after vaccine policy change from oral polio vaccine to inactivated polio vaccine. One hundred and seventy-nine enteroviruses were isolated from the 3394 stool specimens investigated between 1992 and December 2012. Fifty-six out of 107 virus isolates were polioviruses and the remaining were non-polio enteroviruses. Since 2009 after the sequential introduction of IPV in the childhood immunization programme, no Sabin polioviruses were isolated from AFP cases. In 2012, the laboratory AFP surveillance was supplemented with environmental surveillance with sewage sampling. Thirteen Sabin polioviruses were also isolated from sewage in the same year, but no vaccine-derived poliovirus was detected during this period.

  10. Inactivation of Herpes Simplex Viruses by Nonionic Surfactants

    Science.gov (United States)

    Asculai, Samuel S.; Weis, Margaret T.; Rancourt, Martha W.; Kupferberg, A. B.

    1978-01-01

    Nonionic surface-active agents possessing ether or amide linkages between the hydrophillic and hydrophobic portions of the molecule rapidly inactivated the infectivity of herpes simplex viruses. The activity stemmed from the ability of nonionic surfactants to dissolve lipid-containing membranes. This was confirmed by observing surfactant destruction of mammalian cell plasma membranes and herpes simplex virus envelopes. Proprietary vaginal contraceptive formulations containing nonionic surfactants also inactivated herpes simplex virus infectivity. This observation suggests that nonionic surfactants in appropriate formulation could effectively prevent herpes simplex virus transmission. Images PMID:208460

  11. Protective Efficacy of Multiple Vaccine Platforms Against Zika Virus Challenge in Rhesus Monkeys

    OpenAIRE

    Abbink, Peter; Larocca, Rafael A.; De La Barrera, Rafael A.; Bricault, Christine A.; Moseley, Edward T.; Boyd, Michael; Kirilova, Marinela; Li, Zhenfeng; Ng?ang?a, David; Nanayakkara, Ovini; Nityanandam, Ramya; Mercado, Noe B.; Borducchi, Erica N.; Agarwal, Arshi; Brinkman, Amanda L.

    2016-01-01

    Zika virus (ZIKV) is responsible for a major ongoing epidemic in the Americas and has been causally associated with fetal microcephaly. The development of a safe and effective ZIKV vaccine is therefore an urgent global health priority. Here we demonstrate that three different vaccine platforms protect against ZIKV challenge in rhesus monkeys. A purified inactivated virus vaccine induced ZIKV-specific neutralizing antibodies and completely protected monkeys against ZIKV strains from both Brazi...

  12. Viruses, Vaccines and the Public.

    Science.gov (United States)

    Diamond, Judy; McQuillan, Julia; Spiegel, Amy N; Hill, Patricia Wonch; Smith, Rebecca; West, John; Wood, Charles

    Current research in virology is changing public conceptions about vaccines and infectious disease. The University of Nebraska State Museum collaborated with research virologists, science writers, artists and learning researchers to create public outreach materials about viruses and infectious disease. The project, funded by the National Institute of Health's SEPA program, developed comics, a book with Carl Zimmer, and other materials and programs. The project launched three kinds of learning research: 1) a survey of Nebraska adults on their opinions about vaccines and infectious disease; 2) a study comparing the mental models of viruses, vaccines and infection from virologists, teachers, and students; and 3) a controlled study 873 high school students randomly assigned to read either a comic or a text-based essay with the same virus information.

  13. Comparative analysis of the immunogenicity and protective effects of inactivated EV71 vaccines in mice.

    Directory of Open Access Journals (Sweden)

    Qunying Mao

    Full Text Available Enterovirus 71 (EV71 is the major causative agent of hand, foot, and mouth disease (HFMD. Three inactivated EV71 whole-virus vaccines of different strains developed by different manufacturers in mainland China have recently entered clinical trials. Although several studies on these vaccines have been published, a study directly comparing the immunogenicity and protective effects among them has not been carried out, which makes evaluating their relative effectiveness difficult. Thus, properly comparing newly developed vaccines has become a priority, especially in China.This comparative immunogenicity study was carried out on vaccine strains (both live and inactivated, final container products (FCPs without adjuvant, and corresponding FCPs containing adjuvant (FCP-As produced by three manufacturers. These vaccines were evaluated by neutralizing antibody (NAb responses induced by the same or different dosages at one or multiple time points post-immunization. The protective efficacy of the three vaccines was also determined in one-day-old ICR mice born to immunized female mice. Survival rates were observed in these suckling mice after challenge with 20 LD(50 of EV71/048M3C2. Three FCP-As, in a dose of 200 U, generated nearly 100% NAb positivity rates and similar geometric mean titers (GMTs, especially at 14-21 days post-inoculation. However, the dynamic NAb responses were different among three vaccine strains or three FCPs. The FCP-As at the lowest dose used in clinical trials (162 U showed good protective effects in suckling mice against lethal challenge (90-100% survival, while the ED(50 of NAb responses and protective effects varied among three FCP-As.These studies establish a standard method for measuring the immunogenicity of EV71 vaccines in mice. The data generated from our mouse model study indicated a clear dose-response relationship, which is important for vaccine quality control and assessment, especially for predicting protective

  14. 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.

  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. Vaccine platform recombinant measles virus.

    Science.gov (United States)

    Mühlebach, Michael D

    2017-10-01

    The classic development of vaccines is lengthy, tedious, and may not necessarily be successful as demonstrated by the case of HIV. This is especially a problem for emerging pathogens that are newly introduced into the human population and carry the inherent risk of pandemic spread in a naïve population. For such situations, a considerable number of different platform technologies are under development. These are also under development for pathogens, where directly derived vaccines are regarded as too complicated or even dangerous due to the induction of inefficient or unwanted immune responses causing considerable side-effects as for dengue virus. Among platform technologies are plasmid-based DNA vaccines, RNA replicons, single-round infectious vector particles, or replicating vaccine-based vectors encoding (a) critical antigen(s) of the target pathogens. Among the latter, recombinant measles viruses derived from vaccine strains have been tested. Measles vaccines are among the most effective and safest life-attenuated vaccines known. Therefore, the development of Schwarz-, Moraten-, or AIK-C-strain derived recombinant vaccines against a wide range of mostly viral, but also bacterial pathogens was quite straightforward. These vaccines generally induce powerful humoral and cellular immune responses in appropriate animal models, i.e., transgenic mice or non-human primates. Also in the recent first clinical phase I trial, the results have been quite encouraging. The trial indicated the expected safety and efficacy also in human patients, interestingly independent from the level of prevalent anti-measles immunity before the trial. Thereby, recombinant measles vaccines expressing additional antigens are a promising platform for future vaccines.

  17. Vaccination of swine with an inactivated porcine parvovirus vaccine in the presence of passive immunity.

    Science.gov (United States)

    Paul, P S; Mengeling, W L

    1986-02-15

    A study was conducted to determine whether low hemagglutination inhibiting (HI) titers (1:5) for porcine parvovirus (PPV) block the development of immune response to a PPV vaccine. Pigs with low (1:5), medium (1:10 or 1:20), or high (1:40 or 1:80) titers were obtained by IV injections with various amounts of PPV immune serum. Pigs were inoculated with 1 or 2 doses of vaccine and were monitored for serum HI antibodies to PPV. Pigs with low titers responded to vaccine just as well as did the seronegative pigs. The HI titers of pigs with medium titers did not increase after first vaccination. After the second vaccination, however, their titers increased and were similar to those of pigs with low titers. High titers blocked the response to vaccination. The pigs that received 2 doses of vaccine had higher titers than did those of pigs that received 1 dose of vaccine. The results indicated that low titers, which would be expected in gilts at the time of vaccination, do not interfere with immunization by the inactivated PPV vaccine, and that 2 doses of vaccine may provide better and longer lasting immune response to inactivated PPV vaccine and probably longer lasting immunity against PPV-induced reproductive failure.

  18. The efficacy of inactivated West Nile vaccine (WN-VAX) in mice and monkeys.

    Science.gov (United States)

    Muraki, Yuko; Fujita, Takeshi; Matsuura, Masaaki; Fuke, Isao; Manabe, Sadao; Ishikawa, Toyokazu; Okuno, Yoshinobu; Morita, Kouichi

    2015-04-09

    West Nile virus (WNV) belonging to the genus Flavivirus of the family Flaviviridae causes nervous system disorder in humans, horses and birds. Licensed WNV vaccines are available for use in horses but not for humans. We previously developed an inactivated West Nile virus vaccine (WN-VAX) using a seed virus from West Nile virus (WNV NY99) that was originally isolated in New York City in 1999. In this study, we report the immunogenicity of WN-VAX in both mice and non-human primates. The WN-VAX immunized mice showed protection against lethal infection with WNV NY99. The challenge test performed on mice passively immunized with serum from other mice that were previously immunized with WN-VAX confirmed that the neutralizing antibody titers of more than 1log10 protected the passively immunized mice from WNV lethal infection. Furthermore, monkeys (Macaca fascicularis) immunized three times with 2.5 μg, 5 μg or 10 μg/dose of WN-VAX exhibited neutralizing antibodies in their sera with titers of more than 2log10 after the second immunization. The WN-VAX was protective in mice both by active and passive immunizations and was immunogenic in monkeys. These results suggest that the vaccine developed in this study may be a potential WNV vaccine candidate for human use.

  19. 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.

  20. New Strains Intended for the Production of Inactivated Polio Vaccine at Low-Containment After Eradication.

    Science.gov (United States)

    Knowlson, Sarah; Burlison, John; Giles, Elaine; Fox, Helen; Macadam, Andrew J; Minor, Philip D

    2015-12-01

    Poliomyelitis has nearly been eradicated through the efforts of the World Health Organization's Global Eradication Initiative raising questions on containment of the virus after it has been eliminated in the wild. Most manufacture of inactivated polio vaccines currently requires the growth of large amounts of highly virulent poliovirus, and release from a production facility after eradication could be disastrous; WHO have therefore recommended the use of the attenuated Sabin strains for production as a safer option although it is recognised that they can revert to a transmissible paralytic form. We have exploited the understanding of the molecular virology of the Sabin vaccine strains to design viruses that are extremely genetically stable and hyperattenuated. The viruses are based on the type 3 Sabin vaccine strain and have been genetically modified in domain V of the 5' non-coding region by changing base pairs to produce a cassette into which capsid regions of other serotypes have been introduced. The viruses give satisfactory yields of antigenically and immunogenically correct viruses in culture, are without measurable neurovirulence and fail to infect non-human primates under conditions where the Sabin strains will do so.

  1. 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...

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

    Directory of Open Access Journals (Sweden)

    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.

  3. Inactivation of viruses in labile blood derivatives. II. Physical methods

    International Nuclear Information System (INIS)

    Horowitz, B.; Wiebe, M.E.; Lippin, A.; Vandersande, J.; Stryker, M.H.

    1985-01-01

    The thermal inactivation of viruses in labile blood derivatives was evaluated by addition of marker viruses (VSV, Sindbis, Sendai, EMC) to anti-hemophilic factor (AHF) concentrates. The rate of virus inactivation at 60 degrees C was decreased by at least 100- to 700-fold by inclusion of 2.75 M glycine and 50 percent sucrose, or 3.0 M potassium citrate, additives which contribute to retention of protein biologic activity. Nonetheless, at least 10(4) infectious units of each virus was inactivated within 10 hours. Increasing the temperature from 60 to 70 or 80 degrees C caused a 90 percent or greater loss in AHF activity. An even greater decline in the rate of virus inactivation was observed on heating AHF in the lyophilized state, although no loss in AHF activity was observed after 72 hours of heating at 60 degrees C. Several of the proteins present in lyophilized AHF concentrates displayed an altered electrophoretic mobility as a result of exposure to 60 degrees C for 24 hours. Exposure of lyophilized AHF to irradiation from a cobalt 60 source resulted in an acceptable yield of AHF at 1.0, but not at 2.0, megarads. At 1 megarad, greater than or equal to 6.0 logs of VSV and 3.3 logs of Sindbis virus were inactivated

  4. Universal influenza virus vaccines and therapeutic antibodies.

    Science.gov (United States)

    Nachbagauer, R; Krammer, F

    2017-04-01

    Current influenza virus vaccines are effective when well matched to the circulating strains. Unfortunately, antigenic drift and the high diversity of potential emerging zoonotic and pandemic viruses make it difficult to select the right strains for vaccine production. This problem causes vaccine mismatches, which lead to sharp drops in vaccine effectiveness and long response times to manufacture matched vaccines in case of novel pandemic viruses. To provide an overview of universal influenza virus vaccines and therapeutic antibodies in preclinical and clinical development. PubMed and clinicaltrials.gov were used as sources for this review. Universal influenza virus vaccines that target conserved regions of the influenza virus including the haemagglutinin stalk domain, the ectodomain of the M2 ion channel or the internal matrix and nucleoproteins are in late preclinical and clinical development. These vaccines could confer broad protection against all influenza A and B viruses including drift variants and thereby abolish the need for annual re-formulation and re-administration of influenza virus vaccines. In addition, these novel vaccines would enhance preparedness against emerging influenza virus pandemics. Finally, novel therapeutic antibodies against the same conserved targets are in clinical development and could become valuable tools in the fight against influenza virus infection. Both universal influenza virus vaccines and therapeutic antibodies are potential future options for the control of human influenza infections. Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  5. Vaccines, viruses, and voodoo.

    Science.gov (United States)

    Borchers, Andrea T; Keen, Carl L; Shoenfeld, Yehuda; Silva, Joseph; Gershwin, M Eric

    2002-01-01

    Vaccinations are invaluable in protection from a wide variety of diseases that can cause substantial morbidity and mortality. Although a rare complication of vaccination, autoimmune disorders represent one of these morbidities. Recently, widespread public concern has arisen from case reports suggesting that--similar to what has been observed after natural viral infections--there might be an association between specific immunizations and autoimmune diseases. Herein we address the biological plausibility of such a connection, focusing particularly on the examples of hepatitis B, rubella, and measles-mumps-rubella (MMR) vaccinations, and the autoimmune diseases they are potentially associated with. Our review of the available data suggests that, for the general population, the risk: benefit ratio is overwhelmingly in favor of vaccinations. However, the possibility cannot be ruled out that, in genetically susceptible individuals, vaccination can result in the unmasking of an autoimmune disease triggered by the immunization. We also critically examine the existing data suggesting a link between immunization against MMR and autism, and briefly discuss the controversial evidence pointing to a possible relationship between mercury exposure from vaccines and autistic disorders. There is a continued urgent need for rigorously designed and executed studies addressing these potential associations, although the use of vaccinations remains a critical public health tool for protection against infectious disease.

  6. Comparison of Immunogenicity Between Inactivated and Live Attenuated Hepatitis A Vaccines Among Young Adults: A 3-Year Follow-up Study.

    Science.gov (United States)

    Liu, Xue-en; Chen, Hai-ying; Liao, Zheng; Zhou, Yisheng; Wen, Hairong; Peng, Shihui; Liu, Yan; Li, Rui; Li, Jie; Zhuang, Hui

    2015-10-15

    A randomized clinical trial of hepatitis A vaccines (1 or 2 doses of inactivated vaccine [Healive] or 1 dose of live attenuated vaccine [Biovac]) was conducted among adults to evaluate seroprotection rates and geometric mean concentrations of antibody against hepatitis A virus for 36 months. High rates of seroprotection persisted for at least 36 months among adults who received 1 or 2 doses of inactivated hepatitis A vaccine but not among adults who received 1 dose of live attenuated hepatitis A vaccine. The long-term serial monitoring of immunogenicity induced by 1 dose of inactivated hepatitis A vaccine is needed to determine an effective alternative to a 2-dose schedule. NCT01865968. © The Author 2015. 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.

  7. 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

  8. 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

  9. Bovine respiratory syncytial virus (BRSV) pneumonia in beef calf herds despite vaccination

    DEFF Research Database (Denmark)

    Larsen, Lars Erik; Tegtmeier, C.; Pedersen, E.

    2001-01-01

    The present report describes the clinical, pathological, serological and virological findings in calves from 2 larger Danish beef herds experiencing outbreaks of pneumonia. The calves had been vaccinated with an inactivated bovine respiratory syncytial virus (BRSV) vaccine 2 months prior to the o......The present report describes the clinical, pathological, serological and virological findings in calves from 2 larger Danish beef herds experiencing outbreaks of pneumonia. The calves had been vaccinated with an inactivated bovine respiratory syncytial virus (BRSV) vaccine 2 months prior...... that the vaccine induced only sparse levels of antibodies probably due to the presence of maternally derived antibodies at the time of vaccination. Necropsy findings in 5 calves revealed changes typical for infectious pneumonia with involvment of BRSV. In conclusion, vaccination of calves against BRSV in 2 Danish...

  10. 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.

  11. Development of methods to measure virus inactivation in fresh waters.

    OpenAIRE

    Ward, R L; Winston, P E

    1985-01-01

    This study concerns the identification and correction of deficiencies in methods used to measure inactivation rates of enteric viruses seeded into environmental waters. It was found that viable microorganisms in an environmental water sample increased greatly after addition of small amounts of nutrients normally present in the unpurified seed virus preparation. This burst of microbial growth was not observed after seeding the water with purified virus. The use of radioactively labeled poliovi...

  12. Strategic priorities for respiratory syncytial virus (RSV) vaccine development

    Science.gov (United States)

    Anderson, L.J.; Dormitzer, P.R.; Nokes, D.J.; Rappuoli, R.; Roca, A.; Graham, B.S.

    2013-01-01

    Although RSV has been a high priority for vaccine development, efforts to develop a safe and effective vaccine have yet to lead to a licensed product. Clinical and epidemiologic features of RSV disease suggest there are at least 4 distinct target populations for vaccines, the RSV naïve young infant, the RSV naïve child ≥6 months of age, pregnant women (to provide passive protection to newborns), and the elderly. These target populations raise different safety and efficacy concerns and may require different vaccination strategies. The highest priority target population is the RSV naïve child. The occurrence of serious adverse events associated with the first vaccine candidate for young children, formalin inactivated RSV (FI-RSV), has focused vaccine development for the young RSV naïve child on live virus vaccines. Enhanced disease is not a concern for persons previously primed by a live virus infection. A variety of live-attenuated viruses have been developed with none yet achieving licensure. New live-attenuated RSV vaccines are being developed and evaluated that maybe sufficiently safe and efficacious to move to licensure. A variety of subunit vaccines are being developed and evaluated primarily for adults in whom enhanced disease is not a concern. An attenuated parainfluenza virus 3 vector expressing the RSV F protein was evaluated in RSV naïve children. Most of these candidate vaccines have used the RSV F protein in various vaccine platforms including virus-like particles, nanoparticles, formulated with adjuvants, and expressed by DNA or virus vectors. The other surface glycoprotein, the G protein, has also been used in candidate vaccines. We now have tools to make and evaluate a wide range of promising vaccines. Costly clinical trials in the target population are needed to evaluate and select candidate vaccines for advancement to efficacy trials. Better data on RSV-associated mortality in developing countries, better estimates of the risk of long term

  13. Vaccination of influenza a virus decreases transmission rates in pigs

    Directory of Open Access Journals (Sweden)

    Romagosa Anna

    2011-12-01

    Full Text Available Abstract Limited information is available on the transmission and spread of influenza virus in pig populations with differing immune statuses. In this study we assessed differences in transmission patterns and quantified the spread of a triple reassortant H1N1 influenza virus in naïve and vaccinated pig populations by estimating the reproduction ratio (R of infection (i.e. the number of secondary infections caused by an infectious individual using a deterministic Susceptible-Infectious-Recovered (SIR model, fitted on experimental data. One hundred and ten pigs were distributed in ten isolated rooms as follows: (i non-vaccinated (NV, (ii vaccinated with a heterologous vaccine (HE, and (iii vaccinated with a homologous inactivated vaccine (HO. The study was run with multiple replicates and for each replicate, an infected non-vaccinated pig was placed with 10 contact pigs for two weeks and transmission of influenza evaluated daily by analyzing individual nasal swabs by RT-PCR. A statistically significant difference between R estimates was observed between vaccinated and non-vaccinated pigs (p R (95%CI was 1 (0.39-2.09 and 0 for the HE and the HO groups respectively, compared to an Ro value of 10.66 (6.57-16.46 in NV pigs (p

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

    Science.gov (United States)

    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.

  15. Immune response profiles of calves following vaccination with live BCG and inactivated Mycobacterium bovis vaccine candidates.

    Directory of Open Access Journals (Sweden)

    E M D L van der Heijden

    Full Text Available Conventional control and eradication strategies for bovine tuberculosis (BTB face tremendous difficulties in developing countries; countries with wildlife reservoirs, a complex wildlife-livestock-human interface or a lack of veterinary and veterinary public health surveillance. Vaccination of cattle and other species might in some cases provide the only suitable control strategy for BTB, while in others it may supplement existing test-and-slaughter schemes. However, the use of live BCG has several limitations and the global rise of HIV/AIDS infections has furthermore warranted the exploration of inactivated vaccine preparations. The aim of this study was to compare the immune response profiles in response to parenteral vaccination with live BCG and two inactivated vaccine candidates in cattle. Twenty-four mixed breed calves (Bos taurus aged 4-6 months, were allocated to one of four groups and vaccinated sub-cutaneously with live M. bovis BCG (Danish 1331, formalin-inactivated M. bovis BCG, heat-killed M. bovis or PBS/Montanide™ (control. Interferon-γ responsiveness and antibody production were measured prior to vaccination and at weekly intervals thereafter for twelve weeks. At nine weeks post-priming, animals were skin tested using tuberculins and MTBC specific protein cocktails and subsequently challenged through intranodular injection of live M. bovis BCG. The animals in the heat-killed M. bovis group demonstrated strong and sustained cell-mediated and humoral immune responses, significantly higher than the control group in response to vaccination, which may indicate a protective immune profile. Animals in this group showed reactivity to the skin test reagents, confirming good vaccine take. Lastly, although not statistically significant, recovery of BCG after challenge was lowest in the heat-killed M. bovis group. In conclusion, the parenteral heat-killed M. bovis vaccine proved to be clearly immunogenic in cattle in the present study

  16. An Alternative Inactivant for Rift Valley Fever Virus using Cobra Venom-derived L-Amino Oxidase, which is Related to its Immune Potential

    Directory of Open Access Journals (Sweden)

    Ebtesam M Al-Olayan

    Full Text Available ABSTRACT Vaccine improvement depends on the formulation, adjuvant type and inactivant used. The type of formulation may interfere with immunogenicity. The present work aimed to evaluate the inactivation activity and related immune potential of the Cobra venom-derived LAO enzyme compared to the currently used inactivants (BPL and formalin for both animal and human vaccines. The RVF virus was completely inactivated within 6 hrs, 4 hrs and 2 hrs after treatment with Formalin, LAO and BPL, respectively. The vaccine potency [ED50] was arranged in a descending order from formalin (0.016 to BPL (0.005 and LAO (0.002. The total IgG levels, Neutralizing Index (NI and Interferon levels were significantly increased compared to those detected after immunization with the BPL- and Formalin-inactivated vaccine candidates.

  17. 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.

  18. 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.

  19. [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).

  20. 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

  1. Evaluation of immunogenicity and protective properties of inactivated poliovirus vaccines: a new surrogate method for predicting vaccine efficacy.

    Science.gov (United States)

    Dragunsky, Eugenia M; Ivanov, Alexander P; Wells, Virgen R; Ivshina, Anna V; Rezapkin, Gennady V; Abe, Shinobu; Potapova, Svetlana G; Enterline, Joan C; Hashizume, Sou; Chumakov, Konstantin M

    2004-10-15

    An assay for the evaluation of protective properties of inactivated poliovirus vaccines (IPVs) in transgenic (Tg) mice susceptible to poliovirus has been developed and optimized for type 2 IPV. This method was used to compare the immunogenicity and protective properties of experimental IPV produced from the attenuated Sabin strain (sIPV) with those of conventional IPV (cIPV) produced from the wild-type (wt) poliovirus MEF-1 strain. Modified enzyme-linked immunosorbent assays (ELISAs) were used to measure immune response in serum and saliva samples from test mice. Tg mice were vaccinated and were challenged either with wt poliovirus or virulent poliovirus derived from the vaccine strain. Compared with cIPV, sIPV induced lower levels of antibodies and did not completely protect mice against challenge with wt virus but did protect mice against challenge with the virulent vaccine-derived strain. This may be due to an 18% nucleotide difference between the MEF-1 and Sabin 2 strains, resulting in 72 amino acid substitutions and leading to antigenic dissimilarity. Immunological properties of both strains, revealed by cross-neutralization tests and ELISAs, confirmed that MEF-1 possesses broader immunogenicity than does Sabin 2. This animal model may be used for the assessment of new IPVs and of combination vaccines containing an IPV component. Copyright 2004 Infectious Diseases Society of America

  2. Environmental poliovirus surveillance during oral poliovirus vaccine and inactivated poliovirus vaccine use in Córdoba Province, Argentina.

    Science.gov (United States)

    Mueller, Judith E; Bessaud, Maël; Huang, Q Sue; Martinez, Laura C; Barril, Patricia A; Morel, Viviane; Balanant, Jean; Bocacao, Judy; Hewitt, Joanne; Gessner, Brad D; Delpeyroux, Francis; Nates, Silvia V

    2009-03-01

    This study compares the presence of environmental poliovirus in two Argentinean populations using oral poliovirus vaccine (OPV) or inactivated poliovirus vaccine (IPV). From January 2003 to December 2005, Córdoba City used IPV in routine infant immunizations, with the exception of intermittent OPV use in August 2005. Between May 2005 and April 2006, we collected weekly wastewater samples in Córdoba City and the province's three major towns, which continued OPV use at all times. Wastewater samples were processed and analyzed for the presence of poliovirus according to WHO guidelines. During the months of IPV use in Córdoba City, the overall proportion of poliovirus-positive samples was 19%. During an intermittent switch from IPV to OPV, this proportion increased to 100% within 2 months. During the 3 months when IPV was reintroduced to replace OPV, a substantial proportion of samples (25%) remained positive for poliovirus. In the OPV-using sites, on average, 54% of samples were poliovirus positive. Seventy-seven percent of poliovirus isolates showed at least one mutation in the VP1-encoding sequence; the maximum genetic divergence from the Sabin strain was 0.7%. Several isolates showed mutations on attenuation markers in the VP1-encoding sequence. The frequency or type of virus mutation did not differ between periods of IPV and OPV use or by virus serotypes. This study indicates that the sustained transmission of OPV viruses was limited during IPV use in a middle-income country with a temperate climate. The continued importation of poliovirus and genetic instability of vaccine strains even in the absence of sustained circulation suggest that high poliovirus vaccine coverage has to be maintained for all countries until the risk of reintroduction of either wild or vaccine-derived poliovirus is close to zero worldwide.

  3. Next generation inactivated polio vaccine manufacturing to support post polio-eradication biosafety goals.

    Directory of Open Access Journals (Sweden)

    Yvonne E Thomassen

    Full Text Available Worldwide efforts to eradicate polio caused a tipping point in polio vaccination strategies. A switch from the oral polio vaccine, which can cause circulating and virulent vaccine derived polioviruses, to inactivated polio vaccines (IPV is scheduled. Moreover, a manufacturing process, using attenuated virus strains instead of wild-type polioviruses, is demanded to enhance worldwide production of IPV, especially in low- and middle income countries. Therefore, development of an IPV from attenuated (Sabin poliovirus strains (sIPV was pursued. Starting from the current IPV production process based on wild type Salk strains, adaptations, such as lower virus cultivation temperature, were implemented. sIPV was produced at industrial scale followed by formulation of both plain and aluminium adjuvanted sIPV. The final products met the quality criteria, were immunogenic in rats, showed no toxicity in rabbits and could be released for testing in the clinic. Concluding, sIPV was developed to manufacturing scale. The technology can be transferred worldwide to support post polio-eradication biosafety goals.

  4. Feline immunodeficiency virus model for designing HIV/AIDS vaccines.

    Science.gov (United States)

    Yamamoto, Janet K; Sanou, Missa P; Abbott, Jeffrey R; Coleman, James K

    2010-01-01

    Feline immunodeficiency virus (FIV) discovered in 1986 is a lentivirus that causes AIDS in domestic cats. FIV is classified into five subtypes (A-E), and all subtypes and circulating intersubtype recombinants have been identified throughout the world. A commercial FIV vaccine, consisting of inactivated subtype-A and -D viruses (Fel-O-Vax FIV, Fort Dodge Animal Health), was released in the United States in 2002. The United States Department of Agriculture approved the commercial release of Fel-O-Vax FIV based on two efficacy trials using 105 laboratory cats and a major safety trial performed on 689 pet cats. The prototype and commercial FIV vaccines had broad prophylactic efficacy against global FIV subtypes and circulating intersubtype recombinants. The mechanisms of cross-subtype efficacy are attributed to FIV-specific T-cell immunity. Findings from these studies are being used to define the prophylactic epitopes needed for an HIV-1 vaccine for humans.

  5. Phospholipase A2 isolated from the venom of Crotalus durissus terrificus inactivates dengue virus and other enveloped viruses by disrupting the viral envelope.

    Directory of Open Access Journals (Sweden)

    Vanessa Danielle Muller

    Full Text Available The Flaviviridae family includes several virus pathogens associated with human diseases worldwide. Within this family, Dengue virus is the most serious threat to public health, especially in tropical and sub-tropical regions of the world. Currently, there are no vaccines or specific antiviral drugs against Dengue virus or against most of the viruses of this family. Therefore, the development of vaccines and the discovery of therapeutic compounds against the medically most important flaviviruses remain a global public health priority. We previously showed that phospholipase A2 isolated from the venom of Crotalus durissus terrificus was able to inhibit Dengue virus and Yellow fever virus infection in Vero cells. Here, we present evidence that phospholipase A2 has a direct effect on Dengue virus particles, inducing a partial exposure of genomic RNA, which strongly suggests inhibition via the cleavage of glycerophospholipids at the virus lipid bilayer envelope. This cleavage might induce a disruption of the lipid bilayer that causes a destabilization of the E proteins on the virus surface, resulting in inactivation. We show by computational analysis that phospholipase A2 might gain access to the Dengue virus lipid bilayer through the pores found on each of the twenty 3-fold vertices of the E protein shell on the virus surface. In addition, phospholipase A2 is able to inactivate other enveloped viruses, highlighting its potential as a natural product lead for developing broad-spectrum antiviral drugs.

  6. 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.

  7. Next Generation Inactivated Polio Vaccine Manufacturing to Support Post Polio-Eradication Biosafety Goals

    NARCIS (Netherlands)

    Thomassen, Y.E.; Oever, van 't A.G.; Oijen, van M.G.C.T.; Wijffels, R.H.; Pol, van der L.A.; Bakker, W.A.M.

    2013-01-01

    Worldwide efforts to eradicate polio caused a tipping point in polio vaccination strategies. A switch from the oral polio vaccine, which can cause circulating and virulent vaccine derived polioviruses, to inactivated polio vaccines (IPV) is scheduled. Moreover, a manufacturing process, using

  8. Oncolytic viruses as anticancer vaccines

    Directory of Open Access Journals (Sweden)

    Norman eWoller

    2014-07-01

    Full Text Available Oncolytic virotherapy has shown impressive results in preclinical studies and first promising therapeutic outcomes in clinical trials as well. Since viruses are known for a long time as excellent vaccination agents, oncolytic viruses are now designed as novel anticancer agents combining the aspect of lysis-dependent cytoreductive activity with concomitant induction of antitumoral immune responses. Antitumoral immune activation by oncolytic virus infection of tumor tissue comprises both, immediate effects of innate immunity and also adaptive responses for long lasting antitumoral activity which is regarded as the most prominent challenge in clinical oncology. To date, the complex effects of a viral tumor infection on the tumor microenvironment and the consequences for the tumor-infiltrating immune cell compartment are poorly understood. However, there is more and more evidence that a tumor infection by an oncolytic virus opens up a number of options for further immunomodulating interventions such as systemic chemotherapy, generic immunostimulating strategies, dendritic cell-based vaccines, and antigenic libraries to further support clinical efficacy of oncolytic virotherapy.

  9. Development of high-yield influenza B virus vaccine viruses.

    Science.gov (United States)

    Ping, Jihui; Lopes, Tiago J S; Neumann, Gabriele; Kawaoka, Yoshihiro

    2016-12-20

    The burden of human infections with influenza A and B viruses is substantial, and the impact of influenza B virus infections can exceed that of influenza A virus infections in some seasons. Over the past few decades, viruses of two influenza B virus lineages (Victoria and Yamagata) have circulated in humans, and both lineages are now represented in influenza vaccines, as recommended by the World Health Organization. Influenza B virus vaccines for humans have been available for more than half a century, yet no systematic efforts have been undertaken to develop high-yield candidates. Therefore, we screened virus libraries possessing random mutations in the six "internal" influenza B viral RNA segments [i.e., those not encoding the major viral antigens, hemagglutinin (HA) and neuraminidase NA)] for mutants that confer efficient replication. Candidate viruses that supported high yield in cell culture were tested with the HA and NA genes of eight different viruses of the Victoria and Yamagata lineages. We identified combinations of mutations that increased the titers of candidate vaccine viruses in mammalian cells used for human influenza vaccine virus propagation and in embryonated chicken eggs, the most common propagation system for influenza viruses. These influenza B virus vaccine backbones can be used for improved vaccine virus production.

  10. Development of high-yield influenza B virus vaccine viruses

    Science.gov (United States)

    Ping, Jihui; Lopes, Tiago J. S.; Neumann, Gabriele; Kawaoka, Yoshihiro

    2016-01-01

    The burden of human infections with influenza A and B viruses is substantial, and the impact of influenza B virus infections can exceed that of influenza A virus infections in some seasons. Over the past few decades, viruses of two influenza B virus lineages (Victoria and Yamagata) have circulated in humans, and both lineages are now represented in influenza vaccines, as recommended by the World Health Organization. Influenza B virus vaccines for humans have been available for more than half a century, yet no systematic efforts have been undertaken to develop high-yield candidates. Therefore, we screened virus libraries possessing random mutations in the six “internal” influenza B viral RNA segments [i.e., those not encoding the major viral antigens, hemagglutinin (HA) and neuraminidase NA)] for mutants that confer efficient replication. Candidate viruses that supported high yield in cell culture were tested with the HA and NA genes of eight different viruses of the Victoria and Yamagata lineages. We identified combinations of mutations that increased the titers of candidate vaccine viruses in mammalian cells used for human influenza vaccine virus propagation and in embryonated chicken eggs, the most common propagation system for influenza viruses. These influenza B virus vaccine backbones can be used for improved vaccine virus production. PMID:27930325

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

    Science.gov (United States)

    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.

  12. 9 CFR 113.206 - Wart Vaccine, Killed Virus.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Wart Vaccine, Killed Virus. 113.206... AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.206 Wart Vaccine, Killed Virus. Wart Vaccine, Killed Virus, shall be prepared...

  13. 9 CFR 113.209 - Rabies Vaccine, Killed Virus.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Rabies Vaccine, Killed Virus. 113.209... Killed Virus Vaccines § 113.209 Rabies Vaccine, Killed Virus. Rabies Vaccine (Killed Virus) shall be prepared from virus-bearing cell cultures or nerve tissues obtained from animals that have developed rabies...

  14. 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

  15. A step forward in the quality control testing of inactivated rabies vaccines - extensive evaluation of European vaccines by using alternative methods to the in vivo potency tests.

    Science.gov (United States)

    Servat, Alexandre; Kempff, Sébastien; Brogat, Valère; Litaize, Estelle; Schereffer, Jean-Luc; Cliquet, Florence

    2015-03-01

    The mouse challenge test still remains the reference method for the potency determination of human and animal inactivated rabies vaccines, and it is still widely used throughout the world. This test suffers from many disadvantages - it is expensive and time consuming, uses a large number of mice, causes significant animal distress, and suffers from high variability. Recently, the European Pharmacopoeia has recognised the use of a serological potency assay (SPA) as an alternative method to the challenge test. This new test is based on the determination of rabies neutralising antibody titres in vaccinated mice, by using the modified Rapid Fluorescent Focus Inhibition Test (mRFFIT). With the objective of adopting this new method for the batch release of inactivated rabies vaccines, we evaluated its performance on a large collection of rabies vaccines currently assessed in our laboratory. The Fluorescent Antibody Virus Neutralisation test (FAVNt) was used in parallel with the mRFFIT, and the results were compared to the mouse challenge test. Our results demonstrate that the SPA is capable of estimating the potency of vaccines formulated with a potency margin well above the minimum of 1IU/dose. For low potency vaccines, this new method demonstrated some limitations, due to the recurrent invalidation of the assay. We have also demonstrated the superior sensitivity of the FAVNt when compared to the mRFFIT, and the importance of minimising the risk of detecting non-responders in vaccinated mice. 2015 FRAME.

  16. 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...

  17. Successful pseudorabies vaccination in maternally immune piglets using recombinant vaccinia virus vaccines.

    Science.gov (United States)

    Brockmeier, S I; Lager, K M; Mengeling, W L

    1997-01-01

    Three gilts were vaccinated with a NYVAC vaccinia recombinant expressing glycoprotein gD of pseudorabies virus (PRV) (NYVAC/gD). After farrowing, the piglets were allowed to nurse normally to obtain colostral immunity and then were divided into four groups, receiving NYVAC/gD, a NYVAC recombinant expressing glycoprotein gB of PRV (NYVAC/gB), an inactivated PRV vaccine (iPRV), or no vaccine. The piglets were vaccinated twice, three weeks apart beginning at approximately two weeks of age and later challenged with virulent PRV oronasally. Piglets that received NYVAC/gB or iPRV were the best protected based on lack of mortality, lower temperature responses, decreased weight loss and decreased viral shedding after challenge. These results indicate effective strategies for stimulating active immune response while still under the protection of maternal immunity.

  18. 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.

  19. Preformulation study of highly purified inactivated polio vaccine, serotype 3.

    Science.gov (United States)

    Qi, Wei; Zeng, Yuhong; Orgel, Scott; Francon, Alain; Kim, Jae Hyun; Randolph, Theodore W; Carpenter, John F; Middaugh, C Russell

    2014-01-01

    To improve the effectiveness of the polio vaccination campaign, improvements in the thermal stability of the vaccine are being investigated. Here, inactivated polio vaccine, serotype 3 (IPV3) was characterized via a number of biophysical techniques. The size was characterized by transmission electronic microscopy and light scattering. The capsid protein conformation was evaluated by intrinsic fluorescence and circular dichroism (CD), and the D-antigen content by enzyme-linked immunosorbent assay (ELISA). The pH thermal stability of IPV3 (pH 3.0-8.0; 10°C-87.5°C) was evaluated by fluorescence, CD, and static light scattering. The transition temperatures reflect the responses, respectively, of tertiary structure, secondary structure, and size to applied thermal stress. The data were summarized as empirical phase diagrams, and the most stable conditions were found to be pH 7.0 with temperature lower than 40°C. CD detected a higher transition temperature for capsid protein than that for RNA. The effects of certain excipients on IPV3 thermal stability and antigen content were evaluated. The results of their effects, based on intrinsic fluorescence and ELISA, were in good agreement, suggesting the feasibility of applying intrinsic fluorescence as a high-throughput tool for formulation development. The study improves the understanding of IPV3 thermal stability, and provides a starting point for future formulation development of IPV3 and other serotypes. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

  20. 9 CFR 113.215 - Bovine Virus Diarrhea Vaccine, Killed Virus.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Bovine Virus Diarrhea Vaccine, Killed... REQUIREMENTS Killed Virus Vaccines § 113.215 Bovine Virus Diarrhea Vaccine, Killed Virus. Bovine Virus Diarrhea... paragraph. (i) Eight bovine virus diarrhea susceptible calves (five vaccinates and three controls) shall be...

  1. 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

  2. Enteric virus removal inactivation by coal-based media

    Energy Technology Data Exchange (ETDEWEB)

    Gupta, A.; Chaudhuri, M. [Indian Institute of Technology, Kanpur (India). Dept. of Civil Engineering

    1995-02-01

    Four coal-based media, viz. alum-pretreated or ferric hydroxide-impregnated Giridih bituminous coal and lignite (alum-GBC, Fe-GBC; alum-lignite and Fe-Lignite) were laboratory tested to assess their potential in removing/inactivating enteric viruses in water. Batch-sorption screening tests, employing a poliovirus-spiked canal water, indicated high poliovirus sorption by Fe-GBC and alum-GBC in a short contact time of 5 min. Based on the results of further batch-sorption tests, using silver incorporated media (alum/Ag-GBC, alum-GBC-Ag and Fe-GBC-Ag), as well as aesthetic water quality consideration and previous findings on removal of coliforms and turbidity, alum/Ag-GBC, alum-GBC and alum-GBC-AG were included in downflow column studies employing poliovirus-spiked canal water. All three media showed potential in removing/inactivating enteric viruses. In a separate column study employing a joint challenge of poliovirus and rotavirus, alum/Ag-GBC removed 59.3-86.5% of the viruses along with more than 99% reduction in indigenous heterotrophic bacteria. Alum/silver-pretreated bituminous coal medium appears promising for use in household water filters in rural areas of the developing world. However, improved medium preparation to further enhance its efficiency is needed; also, its efficacy in removing/inactivating indigenous enteric bacteria, viruses and protozoa has to be ensured and practicalities or economics of application need to be considered.

  3. Isolation of sabin-like polioviruses from wastewater in a country using inactivated polio vaccine.

    Science.gov (United States)

    Zurbriggen, Sebastian; Tobler, Kurt; Abril, Carlos; Diedrich, Sabine; Ackermann, Mathias; Pallansch, Mark A; Metzler, Alfred

    2008-09-01

    From 2001 to 2004, Switzerland switched from routine vaccination with oral polio vaccine (OPV) to inactivated polio vaccine (IPV), using both vaccines in the intervening period. Since IPV is less effective at inducing mucosal immunity than OPV, this change might allow imported poliovirus to circulate undetected more easily in an increasingly IPV-immunized population. Environmental monitoring is a recognized tool for identifying polioviruses in a community. To look for evidence of poliovirus circulation following cessation of OPV use, two sewage treatment plants located in the Zurich area were sampled from 2004 to 2006. Following virus isolation using either RD or L20B cells, enteroviruses and polioviruses were identified by reverse transcription-PCR. A total of 20 out of 174 wastewater samples were positive for 62 Sabin-like isolates. One isolate from each poliovirus-positive sample was analyzed in more detail. Sequencing the complete viral protein 1 (VP1) capsid coding region, as well as intratypic differentiation (ITD), identified 3 Sabin type 1, 13 Sabin type 2, and 4 Sabin type 3 strains. One serotype 1 strain showed a discordant result in the ITD. Three-quarters of the strains showed mutations within the 5' untranslated region and VP1, known to be associated with reversion to virulence. Moreover, three strains showed heterotypic recombination (S2/S1 and S3/S2/S3). The low number of synonymous mutations and the partial temperature sensitivity are not consistent with extended circulation of these Sabin virus strains. Nevertheless, the continuous introduction of polioviruses into the community emphasizes the necessity for uninterrupted child vaccination to maintain high herd immunity.

  4. Use of an inactivated vaccine for prevention of parvovirus-induced reproductive failure in gilts.

    Science.gov (United States)

    Brown, T T; Whitacre, M D; Robison, O W

    1987-01-15

    Gilts from dams that had been inoculated with inactivated porcine parvovirus (PPV) vaccine before breeding became seronegative to PPV by 26 weeks of age. Vaccination of these gilts with inactivated PPV vaccine at 32 weeks of age resulted in an antibody response that peaked at about 2 weeks after vaccination, with -log10 mean hemagglutination inhibiting (HI) antibody titers of less than 2. In the first-year group (82 gilts), HI titers gradually decreased, 20% of the gilts being seronegative by 6 to 7 weeks after vaccination and 75% being seronegative by 16 weeks after vaccination. In the second-year group, 93 gilts were infected naturally by a field strain of PPV at about 11 weeks after single vaccination with inactivated PPV. Additionally, in the second year, 20 vaccinated and 6 nonvaccinated gilts were immune-challenged with virulent PPV at 10 to 12 weeks after vaccination. Neither field nor challenge PPV infection of vaccinated pregnant gilts caused reproductive failure, even though some of the gilts became seronegative for PPV before challenge. Our findings suggest that single vaccination of gilts with inactivated PPV vaccine should give adequate protection from PPV-induced reproductive failure, even though serum HI titers decrease to an undetectable level shortly before PPV infection.

  5. 9 CFR 113.212 - Bursal Disease Vaccine, Killed Virus.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Bursal Disease Vaccine, Killed Virus..., DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.212 Bursal Disease Vaccine, Killed Virus. Bursal Disease Vaccine...

  6. 9 CFR 113.204 - Mink Enteritis Vaccine, Killed Virus.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Mink Enteritis Vaccine, Killed Virus..., DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.204 Mink Enteritis Vaccine, Killed Virus. Mink Enteritis Vaccine...

  7. 9 CFR 113.312 - Rabies Vaccine, Live Virus.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Rabies Vaccine, Live Virus. 113.312... Virus Vaccines § 113.312 Rabies Vaccine, Live Virus. Rabies Vaccine shall be prepared from virus-bearing... administration. (iii) Observe all animals for signs of rabies until scheduled time to sacrifice. If animals show...

  8. Vaccines to Prevent Cancers Not Caused by Viruses - Annual Plan

    Science.gov (United States)

    We have vaccines against viruses that cause cancer, but what about vaccines for cancers not caused by viruses? Learn about NCI's development of safe and effective vaccines for cancers not caused by infectious agents.

  9. A replication-deficient rabies virus vaccine expressing Ebola virus glycoprotein is highly attenuated for neurovirulence

    International Nuclear Information System (INIS)

    Papaneri, Amy B.; Wirblich, Christoph; Cann, Jennifer A.; Cooper, Kurt; Jahrling, Peter B.; Schnell, Matthias J.; Blaney, Joseph E.

    2012-01-01

    We are developing inactivated and live-attenuated rabies virus (RABV) vaccines expressing Ebola virus (EBOV) glycoprotein for use in humans and endangered wildlife, respectively. Here, we further characterize the pathogenesis of the live-attenuated RABV/EBOV vaccine candidates in mice in an effort to define their growth properties and potential for safety. RABV vaccines expressing GP (RV-GP) or a replication-deficient derivative with a deletion of the RABV G gene (RVΔG-GP) are both avirulent after intracerebral inoculation of adult mice. Furthermore, RVΔG-GP is completely avirulent upon intracerebral inoculation of suckling mice unlike parental RABV vaccine or RV-GP. Analysis of RVΔG-GP in the brain by quantitative PCR, determination of virus titer, and immunohistochemistry indicated greatly restricted virus replication. In summary, our findings indicate that RV-GP retains the attenuation phenotype of the live-attenuated RABV vaccine, and RVΔG-GP would appear to be an even safer alternative for use in wildlife or consideration for human use.

  10. A replication-deficient rabies virus vaccine expressing Ebola virus glycoprotein is highly attenuated for neurovirulence

    Energy Technology Data Exchange (ETDEWEB)

    Papaneri, Amy B. [Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, MD 21702 (United States); Wirblich, Christoph [Department of Microbiology and Immunology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107 (United States); Cann, Jennifer A.; Cooper, Kurt [Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick MD, 21702 (United States); Jahrling, Peter B. [Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, MD 21702 (United States); Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick MD, 21702 (United States); Schnell, Matthias J., E-mail: matthias.schnell@jefferson.edu [Department of Microbiology and Immunology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107 (United States); Jefferson Vaccine Center, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107 (United States); Blaney, Joseph E., E-mail: jblaney@niaid.nih.gov [Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, MD 21702 (United States)

    2012-12-05

    We are developing inactivated and live-attenuated rabies virus (RABV) vaccines expressing Ebola virus (EBOV) glycoprotein for use in humans and endangered wildlife, respectively. Here, we further characterize the pathogenesis of the live-attenuated RABV/EBOV vaccine candidates in mice in an effort to define their growth properties and potential for safety. RABV vaccines expressing GP (RV-GP) or a replication-deficient derivative with a deletion of the RABV G gene (RV{Delta}G-GP) are both avirulent after intracerebral inoculation of adult mice. Furthermore, RV{Delta}G-GP is completely avirulent upon intracerebral inoculation of suckling mice unlike parental RABV vaccine or RV-GP. Analysis of RV{Delta}G-GP in the brain by quantitative PCR, determination of virus titer, and immunohistochemistry indicated greatly restricted virus replication. In summary, our findings indicate that RV-GP retains the attenuation phenotype of the live-attenuated RABV vaccine, and RV{Delta}G-GP would appear to be an even safer alternative for use in wildlife or consideration for human use.

  11. Validation of γ-radiation and ultraviolet as a new inactivators for foot and mouth disease virus in comparison with the traditional methods

    Directory of Open Access Journals (Sweden)

    Safy El din Mahdy

    2015-09-01

    Full Text Available Aim: The present work deals with different methods for foot and mouth disease virus (FMDV inactivation for serotypes O/pan Asia, A/Iran05, and SAT-2/2012 by heat, gamma radiation, and ultraviolet (UV in comparison with the traditional methods and their effects on the antigenicity of viruses for production of inactivated vaccines. Materials and Methods: FMDV types O/pan Asia, A/Iran05, and SAT-2/2012 were propagated in baby hamster kidney 21 (BHK21 and titrated then divided into five parts; the first part inactivated with heat, the second part inactivated with gamma radiation, the third part inactivated with UV light, the fourth part inactivated with binary ethylamine, and the last part inactivated with combination of binary ethylamine and formaldehyde (BEI+FA. Evaluate the method of inactivation via inoculation in BHK21, inoculation in suckling baby mice and complement fixation test then formulate vaccine using different methods of inactivation then applying the quality control tests to evaluate each formulated vaccine. Results: The effect of heat, gamma radiation, and UV on the ability of replication of FMDV "O/pan Asia, A/Iran05, and SAT-2/2012" was determined through BHK cell line passage. Each of the 9 virus aliquots titer 108 TCID50 (3 for each strain were exposed to 37, 57, and 77°C for 15, 30, and 45 min. Similarly, another 15 aliquots (5 for each strain contain 1 mm depth of the exposed samples in petri-dish was exposed to UV light (252.7 nm wavelength: One foot distance for 15, 30, 45, 60, and 65 min. Different doses of gamma radiation (10, 20, 25, 30, 35, 40, 45, 50, 55, and 60 KGy were applied in a dose rate 0.551 Gy/s for each strain and repeated 6 times for each dose. FMDV (O/pan Asia, A/Iran05, and SAT-2/2012 were inactivated when exposed to heat ≥57°C for 15 min. The UV inactivation of FMDV (O/pan Asia and SAT-2 was obtained within 60 min and 65 min for type A/Iran05. The ideal dose for inactivation of FMDV (O/pan Asia, A

  12. The mutable vaccine for mutable viruses.

    Science.gov (United States)

    Cascalho, Marilia; Balin, Samuel J; Platt, Jeffrey L

    2017-06-01

    Mutable viruses, such as HIV, pose difficult obstacles to prevention and/or control by vaccination. Mutable viruses rapidly diversify in populations and in individuals, impeding development of effective vaccines. We devised the 'mutable vaccine' to appropriate the properties of mutable viruses that undermine conventional strategies. The vaccine consists of a DNA construct encoding viral antigen and regulatory sequences that upon delivery to B cells target the enzymatic apparatus of 'somatic hypermutation' causing the construct to mutate one million-times baseline rates and allowing production and presentation of antigen variants. We postulate the mutable vaccine might thus anticipate diversification of mutable viruses, allowing direct control or slowing of evolution. Initial work presented here should encourage consideration of this novel approach.

  13. Inactive vaccine derived from velogenic strain of local Newcastle disease virus .

    Directory of Open Access Journals (Sweden)

    Darminto

    1996-03-01

    Full Text Available The objective of this research is to evaluate an application of an inactive Newcastle disease (ND vaccine derived from velogenic strain of local Newcastle disease virus (NDV. In this research . the Ira strain of velogenic ND virus was grown in specific pathogen free (SPF eggs and then was inactivated by formalin at a final concentration of 1 :1,000 at 4°C. The inactive antigen was then emulsified with an oil adjuvant or aluminium hydroxide gel before being administered for vaccination in layers and compared to a commercial inactive ND vaccine . Results indicated that application of these inactivated ND vaccines for booster vaccination following vaccination with an active lentogenic ND virus in pullets nearly producing eggs, resulted in high antibody titre which persisted for considerable long period of time and capable of protecting layers from sick of ND and from reducing egg production . Hence, it could be concluded that the inactivated vaccine emulsified in either oil-adjuvant (lanolin-paraffin or aluminium hydroxide gel were considered to be highly immunogenic and capable of protecting layers from sick of ND and from reducing egg production

  14. Radiation inactivation of animal viruses in culture fluid and sewage; a case study

    International Nuclear Information System (INIS)

    Groneman, A.F.; Frenkel, S.; Terpstra, C.

    1977-01-01

    Inactivation studies of different animal viruses were performed with gamma irradiation from a 60 Co-source to evaluate the technical and economic feasibility of sterilization of sewage of a veterinary institute involved in research on virus diseases and the production of virus vaccines. The D 10 values for swine fever virus, foot-and-mouth disease virus (FMDV) and swine vesicular disease virus (SVDV) irradiated in culture medium at 0degC were 1.8, 4.5, and 5.9 kGy (0.18, 0.45, and 0.59 Mrad), respectively. Suspensions of SVDV and FMDV were mixed with raw sludge and irradiated at 8degC. Raw sludge had a protecting effect on FMDV, if compared to culture fluid, increasing the D 10 value significantly to 6.5 kGy (0.65 Mrad). No similar protective effect was observed in the case of SVDV. Addition of 0.2 M NaBr did not significantly increase the radiosensitivity of these two viruses. The technical and economic feasibility for sterilization of sewage and sludge by 60 Co-gamma irradiation are discussed

  15. Laser inactivation of pathogenic viruses in water

    Science.gov (United States)

    Grishkanich, Alexander; Zhevlakov, Alexander; Kascheev, Sergey; Sidorov, Igor; Ruzankina, Julia; Yakovlev, Alexey; Mak, Andrey

    2016-03-01

    Currently there is a situation that makes it difficult to provide the population with quality drinking water for the sanitary-hygienic requirements. One of the urgent problems is the need for water disinfection. Since the emergence of microorganisms that are pathogens transmitted through water such as typhoid, cholera, etc. requires constant cleansing of waters against pathogenic bacteria. In the water treatment process is destroyed up to 98% of germs, but among the remaining can be pathogenic viruses, the destruction of which requires special handling. As a result, the conducted research the following methods have been proposed for combating harmful microorganisms: sterilization of water by laser radiation and using a UV lamp.

  16. New Kids on the Block: RNA-Based Influenza Virus Vaccines.

    Science.gov (United States)

    Scorza, Francesco Berlanda; Pardi, Norbert

    2018-04-01

    RNA-based immunization strategies have emerged as promising alternatives to conventional vaccine approaches. A substantial body of published work demonstrates that RNA vaccines can elicit potent, protective immune responses against various pathogens. Consonant with its huge impact on public health, influenza virus is one of the best studied targets of RNA vaccine research. Currently licensed influenza vaccines show variable levels of protection against seasonal influenza virus strains but are inadequate against drifted and pandemic viruses. In recent years, several types of RNA vaccines demonstrated efficacy against influenza virus infections in preclinical models. Additionally, comparative studies demonstrated the superiority of some RNA vaccines over the currently used inactivated influenza virus vaccines in animal models. Based on these promising preclinical results, clinical trials have been initiated and should provide valuable information about the translatability of the impressive preclinical data to humans. This review briefly describes RNA-based vaccination strategies, summarizes published preclinical and clinical data, highlights the roadblocks that need to be overcome for clinical applications, discusses the landscape of industrial development, and shares the authors' personal perspectives about the future of RNA-based influenza virus vaccines.

  17. Inactivation of virus in solution by cold atmospheric pressure plasma: identification of chemical inactivation pathways

    Science.gov (United States)

    Aboubakr, Hamada A.; Gangal, Urvashi; Youssef, Mohammed M.; Goyal, Sagar M.; Bruggeman, Peter J.

    2016-05-01

    Cold atmospheric pressure plasma (CAP) inactivates bacteria and virus through in situ production of reactive oxygen and nitrogen species (RONS). While the bactericidal and virucidal efficiency of plasmas is well established, there is limited knowledge about the chemistry leading to the pathogen inactivation. This article describes a chemical analysis of the CAP reactive chemistry involved in the inactivation of feline calicivirus. We used a remote radio frequency CAP produced in varying gas mixtures leading to different plasma-induced chemistries. A study of the effects of selected scavengers complemented with positive control measurements of relevant RONS reveal two distinctive pathways based on singlet oxygen and peroxynitrous acid. The first mechanism is favored in the presence of oxygen and the second in the presence of air when a significant pH reduction is induced in the solution by the plasma. Additionally, smaller effects of the H2O2, O3 and \\text{NO}2- produced were also found. Identification of singlet oxygen-mediated 2-imidazolone/2-oxo-His (His  +14 Da)—an oxidative modification of His 262 comprising the capsid protein of feline calicivirus links the plasma induced singlet oxygen chemistry to viral inactivation.

  18. A chikungunya fever vaccine utilizing an insect-specific virus platform.

    Science.gov (United States)

    Erasmus, Jesse H; Auguste, Albert J; Kaelber, Jason T; Luo, Huanle; Rossi, Shannan L; Fenton, Karla; Leal, Grace; Kim, Dal Y; Chiu, Wah; Wang, Tian; Frolov, Ilya; Nasar, Farooq; Weaver, Scott C

    2017-02-01

    Traditionally, vaccine development involves tradeoffs between immunogenicity and safety. Live-attenuated vaccines typically offer rapid and durable immunity but have reduced safety when compared to inactivated vaccines. In contrast, the inability of inactivated vaccines to replicate enhances safety at the expense of immunogenicity, often necessitating multiple doses and boosters. To overcome these tradeoffs, we developed the insect-specific alphavirus, Eilat virus (EILV), as a vaccine platform. To address the chikungunya fever (CHIKF) pandemic, we used an EILV cDNA clone to design a chimeric virus containing the chikungunya virus (CHIKV) structural proteins. The recombinant EILV/CHIKV was structurally identical at 10 Å to wild-type CHIKV, as determined by single-particle cryo-electron microscopy, and it mimicked the early stages of CHIKV replication in vertebrate cells from attachment and entry to viral RNA delivery. Yet the recombinant virus remained completely defective for productive replication, providing a high degree of safety. A single dose of EILV/CHIKV produced in mosquito cells elicited rapid (within 4 d) and long-lasting (>290 d) neutralizing antibodies that provided complete protection in two different mouse models. In nonhuman primates, EILV/CHIKV elicited rapid and robust immunity that protected against viremia and telemetrically monitored fever. Our EILV platform represents the first structurally native application of an insect-specific virus in preclinical vaccine development and highlights the potential application of such viruses in vaccinology.

  19. Full Genome Characterisation of Bluetonge Virus Seroptype 6 from the Netherlands 2008 and Comparison to Other Field and Vaccine Strains

    NARCIS (Netherlands)

    Maan, S.; Maan, N.S.; Rijn, van P.A.; Gennip, van H.G.P.; Sanders, A.A.; Wright, I.M.; Batten, C.; Hoffmann, B.; Eschbaumer, M.; Oura, C.A.L.; Potgieter, C.; Nomikou, K.; Mertens, P.P.C.

    2010-01-01

    In mid September 2008, clinical signs of bluetongue (particularly coronitis) were observed in cows on three different farms in eastern Netherlands (Luttenberg, Heeten, and Barchem), two of which had been vaccinated with an inactivated BTV-8 vaccine (during May-June 2008). Bluetongue virus (BTV)

  20. 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...

  1. [Serologic response in dogs after a mass primary antirabies vaccination (inactivated vaccine) at Pikine Dakar (Senegal)].

    Science.gov (United States)

    Akakpo, A J; Mbou, G; Bornarel, P; Sarradin, P; Bada Alambjedi, R

    1993-01-01

    Mass antirabic vaccination campaign, allowed in 1987, the immunization of 514 pet dogs against rabies at Pikine, a suburban area of Dakar. Dogs received one subcutaneous dose of inactivated tissue culture rabies vaccine (RABISIN, Rhône Mérieux France). Mean antibodies titles in ELISA on days 30, 180 and 360 after vaccination, are respectively 4.78; 1.55 and 0.25 IU/ml. In the same time the proportions of protected animals are 74%, 81% and 7%. This results is compared with those obtained in other countries. The rapid decrease of antibodies suggest the role of poor general health of animals such as malnutrition, infections, external and internal parasitemia.

  2. Vaccination against H9N2 avian influenza virus reduces bronchus-associated lymphoid tissue formation in cynomolgus macaques after intranasal virus challenge infection.

    Science.gov (United States)

    Nakayama, Misako; Ozaki, Hiroichi; Itoh, Yasushi; Soda, Kosuke; Ishigaki, Hirohito; Okamatsu, Masatoshi; Sakoda, Yoshihiro; Park, Chun-Ho; Tsuchiya, Hideaki; Kida, Hiroshi; Ogasawara, Kazumasa

    2016-12-01

    H9N2 avian influenza virus causes sporadic human infection. Since humans do not possess acquired immunity specific to this virus, we examined the pathogenicity of an H9N2 virus isolated from a human and then analyzed protective effects of a vaccine in cynomolgus macaques. After intranasal challenge with A/Hong Kong/1073/1999 (H9N2) (HK1073) isolated from a human patient, viruses were isolated from nasal and tracheal swabs in unvaccinated macaques with mild fever and body weight loss. A formalin-inactivated H9N2 whole particle vaccine derived from our virus library was subcutaneously inoculated to macaques. Vaccination induced viral antigen-specific IgG and neutralization activity in sera. After intranasal challenge with H9N2, the virus was detected only the day after inoculation in the vaccinated macaques. Without vaccination, many bronchus-associated lymphoid tissues (BALTs) were formed in the lungs after infection, whereas the numbers of BALTs were smaller and the cytokine responses were weaker in the vaccinated macaques than those in the unvaccinated macaques. These findings indicate that the H9N2 avian influenza virus HK1073 is pathogenic in primates but seems to cause milder symptoms than does H7N9 influenza virus as found in our previous studies and that a formalin-inactivated H9N2 whole particle vaccine induces protective immunity against H9N2 virus. © 2016 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.

  3. 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

  4. Development of vaccines against Zika virus.

    Science.gov (United States)

    Poland, Gregory A; Kennedy, Richard B; Ovsyannikova, Inna G; Palacios, Ricardo; Ho, Paulo Lee; Kalil, Jorge

    2018-01-25

    Zika virus is an emerging pathogen of substantial public health concern to human beings. Although most infections are asymptomatic or present with benign, self-limited symptoms, a small percentage of patients have complications, such as congenital anomalies in the developing fetus of pregnant women infected with the virus and neurological complications (eg, Guillain-Barré syndrome). To date, there is no vaccine, antiviral drug, or other modality available to prevent or treat Zika virus infection. In this Review, we examine vaccine development efforts for Zika virus to date and research gaps in the development of candidate vaccines against Zika virus. Top research priorities should include development of a better understanding of immunity to Zika virus to establish clear correlates of protection; determination of what effect, if any, Zika vaccine-induced immune responses will have on subsequent dengue virus infection; evaluation of vaccine immunogenicity and efficacy in healthy adults and in the various subpopulations affected by Zika virus infection (children, pregnant women, women of childbearing age, and eldery people); and identification of the molecular mechanisms that underlie birth defects and neurological sequelae related to Zika virus. Copyright © 2018 Elsevier Ltd. All rights reserved.

  5. 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.

  6. 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)

  7. Combined virus-like particle and fusion protein-encoding DNA vaccination of cotton rats induces protection against respiratory syncytial virus without causing vaccine-enhanced disease

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Hye Suk; Lee, Young-Tae; Kim, Ki-Hye; Park, Soojin; Kwon, Young-Man; Lee, Youri; Ko, Eun-Ju; Jung, Yu-Jin [Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA (United States); Lee, Jong Seok [Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA (United States); National Institute of Biological Resources, Incheon (Korea, Republic of); Kim, Yu-Jin [Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA (United States); Lee, Yu-Na; Kim, Min-Chul [Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA (United States); Animal and Plant Quarantine Agency, Gyeonggi-do, Gimcheon, Gyeongsangbukdo (Korea, Republic of); Cho, Minkyoung [Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA (United States); Kang, Sang-Moo, E-mail: skang24@gsu.edu [Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA (United States)

    2016-07-15

    A safe and effective vaccine against respiratory syncytial virus (RSV) should confer protection without causing vaccine-enhanced disease. Here, using a cotton rat model, we investigated the protective efficacy and safety of an RSV combination vaccine composed of F-encoding plasmid DNA and virus-like particles containing RSV fusion (F) and attachment (G) glycoproteins (FFG-VLP). Cotton rats with FFG-VLP vaccination controlled lung viral replication below the detection limit, and effectively induced neutralizing activity and antibody-secreting cell responses. In comparison with formalin inactivated RSV (FI-RSV) causing severe RSV disease after challenge, FFG-VLP vaccination did not cause weight loss, airway hyper-responsiveness, IL-4 cytokines, histopathology, and infiltrates of proinflammatory cells such as eosinophils. FFG-VLP was even more effective in preventing RSV-induced pulmonary inflammation than live RSV infections. This study provides evidence that FFG-VLP can be developed into a safe and effective RSV vaccine candidate. - Highlights: • Combined RSV FFG VLP vaccine is effective in inducing F specific responses. • FFG VLP vaccine confers RSV neutralizing activity and viral control in cotton rats. • Cotton rats with RSV FFG VLP vaccination do not show vaccine-enhanced disease. • Cotton rats with FFG VLP vaccine induce F specific antibody secreting cell responses. • Cotton rats with FFG VLP do not induce lung cellular infiltrates and Th2 cytokine.

  8. Combined virus-like particle and fusion protein-encoding DNA vaccination of cotton rats induces protection against respiratory syncytial virus without causing vaccine-enhanced disease

    International Nuclear Information System (INIS)

    Hwang, Hye Suk; Lee, Young-Tae; Kim, Ki-Hye; Park, Soojin; Kwon, Young-Man; Lee, Youri; Ko, Eun-Ju; Jung, Yu-Jin; Lee, Jong Seok; Kim, Yu-Jin; Lee, Yu-Na; Kim, Min-Chul; Cho, Minkyoung; Kang, Sang-Moo

    2016-01-01

    A safe and effective vaccine against respiratory syncytial virus (RSV) should confer protection without causing vaccine-enhanced disease. Here, using a cotton rat model, we investigated the protective efficacy and safety of an RSV combination vaccine composed of F-encoding plasmid DNA and virus-like particles containing RSV fusion (F) and attachment (G) glycoproteins (FFG-VLP). Cotton rats with FFG-VLP vaccination controlled lung viral replication below the detection limit, and effectively induced neutralizing activity and antibody-secreting cell responses. In comparison with formalin inactivated RSV (FI-RSV) causing severe RSV disease after challenge, FFG-VLP vaccination did not cause weight loss, airway hyper-responsiveness, IL-4 cytokines, histopathology, and infiltrates of proinflammatory cells such as eosinophils. FFG-VLP was even more effective in preventing RSV-induced pulmonary inflammation than live RSV infections. This study provides evidence that FFG-VLP can be developed into a safe and effective RSV vaccine candidate. - Highlights: • Combined RSV FFG VLP vaccine is effective in inducing F specific responses. • FFG VLP vaccine confers RSV neutralizing activity and viral control in cotton rats. • Cotton rats with RSV FFG VLP vaccination do not show vaccine-enhanced disease. • Cotton rats with FFG VLP vaccine induce F specific antibody secreting cell responses. • Cotton rats with FFG VLP do not induce lung cellular infiltrates and Th2 cytokine.

  9. Protective Efficacy of Multiple Vaccine Platforms Against Zika Virus Challenge in Rhesus Monkeys

    Science.gov (United States)

    Abbink, Peter; Larocca, Rafael A.; De La Barrera, Rafael A.; Bricault, Christine A.; Moseley, Edward T.; Boyd, Michael; Kirilova, Marinela; Li, Zhenfeng; Ng’ang’a, David; Nanayakkara, Ovini; Nityanandam, Ramya; Mercado, Noe B.; Borducchi, Erica N.; Agarwal, Arshi; Brinkman, Amanda L.; Cabral, Crystal; Chandrashekar, Abishek; Giglio, Patricia B.; Jetton, David; Jimenez, Jessica; Lee, Benjamin C.; Mojta, Shanell; Molloy, Katherine; Shetty, Mayuri; Neubauer, George H.; Stephenson, Kathryn E.; Peron, Jean Pierre S.; Zanotto, Paolo M. de A.; Misamore, Johnathan; Finneyfrock, Brad; Lewis, Mark G.; Alter, Galit; Modjarrad, Kayvon; Jarman, Richard G.; Eckels, Kenneth H.; Michael, Nelson L.; Thomas, Stephen J.; Barouch, Dan H.

    2017-01-01

    Zika virus (ZIKV) is responsible for a major ongoing epidemic in the Americas and has been causally associated with fetal microcephaly. The development of a safe and effective ZIKV vaccine is therefore an urgent global health priority. Here we demonstrate that three different vaccine platforms protect against ZIKV challenge in rhesus monkeys. A purified inactivated virus vaccine induced ZIKV-specific neutralizing antibodies and completely protected monkeys against ZIKV strains from both Brazil and Puerto Rico. Purified immunoglobulin from vaccinated monkeys conferred passive protection in adoptive transfer studies. A plasmid DNA vaccine and a single-shot recombinant rhesus adenovirus serotype 52 vector expressing ZIKV prM-Env also elicited neutralizing antibodies and completely protected monkeys against ZIKV challenge. These data support the rapid clinical development of ZIKV vaccines for humans. PMID:27492477

  10. Recombinant egg drop syndrome subunit vaccine offers an alternative to virus propagation in duck eggs.

    Science.gov (United States)

    Gutter, B; Fingerut, E; Gallili, G; Eliahu, D; Perelman, B; Finger, A; Pitcovski, J

    2008-02-01

    Egg drop syndrome (EDS) virus vaccines are routinely produced in embryonated duck eggs (Solyom et al., 1982). This procedure poses the risk of dissemination of pathogens, such as avian influenza virus, as the eggs used are not from specific pathogen free birds. To address this problem, the knob and part of the shaft domain of the fibre protein of the EDS virus (termed knob-s) were expressed in Escherichia coli and assessed as a subunit vaccine. A single vaccination with the recombinant protein induced the production of anti-EDS virus antibodies, as detected by haemagglutination inhibition, enzyme-linked immunosorbent assay and virus neutralization tests, for at least 20 weeks. A positive correlation was demonstrated between these three assays. A dose-response assessment showed that the vaccine was effective over the range of 2 to 64 microg protein per dose. Two vaccinations with the recombinant protein, administered before the onset of lay, induced high haemagglutination inhibition antibody titres, comparable with those induced by an inactivated whole-virus vaccine. The vaccine did not have any adverse effects on egg production, quality or weight. The present study has shown that two vaccinations with the recombinant knob-s protein elicited high neutralizing antibody titres that persisted for more than 50 weeks of lay.

  11. Primary vaccination of adults with reduced antigen-content diphtheria-tetanus-acellular pertussis or dTpa-inactivated poliovirus vaccines compared to diphtheria-tetanus-toxoid vaccines.

    NARCIS (Netherlands)

    Theeten, H.; Rumke, H.C.; Hoppener, F.J.; Vilatimo, R.; Narejos, S.; Damme, P. van; Hoet, B.

    2007-01-01

    OBJECTIVE: To evaluate immunogenicity and reactogenicity of primary vaccination with reduced-antigen-content diphtheria-tetanus-acellular pertussis (dTpa) or dTpa-inactivated poliovirus (dTpa-IPV) vaccine compared to diphtheria-tetanus-toxoid vaccines (Td) in adults > or = 40 years of age without

  12. Human papilloma virus vaccine associated uveitis.

    Science.gov (United States)

    Holt, Henry D; Hinkle, David M; Falk, Naomi S; Fraunfelder, Frederick T; Fraunfelder, Frederick W

    2014-03-01

    To report a possible association between human papilloma virus (HPV) vaccination and uveitis. Spontaneous reports from the National Registry of Drug-Induced Ocular Side effects, World Health Organization and Food and Drug Administration were collected on uveitis associated with human papilloma virus vaccination. A MEDLINE search was performed using keywords "uveitis," "iritis," "iridocyclitis," "human papilloma virus," "Cervarix", and "Gardasil." Data garnered from spontaneous reports included the age, gender, adverse drug reaction (ADR), date of administration, concomitant administration of other vaccinations, time until onset of ADR, other systemic reactions, and dechallenge and rechallenge data. A total of 24 case reports of uveitis associated with human papilloma virus vaccination were identified, all cases were female, and the median age was 17. Median time from HPV vaccination to reported ADR was 30 days (range 0-476 days). According to World Health Organization criteria, the relationship between human papilloma virus vaccination and uveitis is "possible." Causality assessments are based on the time relationship of drug administration, uveitis development and re-challenge data. Clinicians should be aware of a possible bilateral uveitis and papillitis following HPV vaccination.

  13. Vaccines in Development against West Nile Virus

    Directory of Open Access Journals (Sweden)

    Frederic Tangy

    2013-09-01

    Full Text Available West Nile encephalitis emerged in 1999 in the United States, then rapidly spread through the North American continent causing severe disease in human and horses. Since then, outbreaks appeared in Europe, and in 2012, the United States experienced a new severe outbreak reporting a total of 5,387 cases of West Nile virus (WNV disease in humans, including 243 deaths. So far, no human vaccine is available to control new WNV outbreaks and to avoid worldwide spreading. In this review, we discuss the state-of-the-art of West Nile vaccine development and the potential of a novel safe and effective approach based on recombinant live attenuated measles virus (MV vaccine. MV vaccine is a live attenuated negative-stranded RNA virus proven as one of the safest, most stable and effective human vaccines. We previously described a vector derived from the Schwarz MV vaccine strain that stably expresses antigens from emerging arboviruses, such as dengue, West Nile or chikungunya viruses, and is strongly immunogenic in animal models, even in the presence of MV pre-existing immunity. A single administration of a recombinant MV vaccine expressing the secreted form of WNV envelope glycoprotein elicited protective immunity in mice and non-human primates as early as two weeks after immunization, indicating its potential as a human vaccine.

  14. UV light inactivation of hepatitis A virus, Aichi virus, and feline calicivirus on strawberries, green onions, and lettuce.

    Science.gov (United States)

    Fino, Viviana R; Kniel, Kalmia E

    2008-05-01

    A majority of illnesses caused by foodborne viruses are associated with fresh produce. Fruits and vegetables may be considered high-risk foods, as they are often consumed raw without a specific inactivation step. Therefore, there is a need to evaluate nonthermal treatments for the inactivation of foodborne pathogens. This study investigates the UV inactivation of three viruses: feline calicivirus (a surrogate for norovirus), and two picornaviruses, hepatitis A virus and Aichi virus. Three produce types were selected for their different surface topographies and association with outbreaks. Green onions, lettuce, and strawberries were individually spot inoculated with 10(7) to 10(9) 50% tissue culture infective doses (TCID50) of each virus per ml and exposed to UV light at various doses (culture and compared with untreated recovered virus. UV light applied to contaminated lettuce resulted in inactivation of 4.5 to 4.6 log TCID50/ml; for contaminated green onions, inactivation ranged from 2.5 to 5.6 log TCID50/ml; and for contaminated strawberries, inactivation ranged from 1.9 to 2.6 log TCID50/ml for the three viruses tested. UV light inactivation on the surface of lettuce is more effective than inactivation on the other two produce items. Consistently, the lowest results were observed in the inactivation of viruses on strawberries. No significant differences (P > 0.05) for virus inactivation were observed among the three doses applied (40, 120, and 240 mW s/cm2) on the produce, with the exception of hepatitis A virus and Aichi virus inactivation on green onions, where inactivation continued at 120 mW s/cm2 (P < 0.05).

  15. Pengembangan Vaksin Inaktif Tetelo Genotipe VII Isolat Lokal pada Kondisi Laboratorium. (DEVELOPMENT OF TETELO INACTIVATED VACCINE GENOTYPE VII LOCAL ISOLATE IN LABORATORY CONDITION

    Directory of Open Access Journals (Sweden)

    Risa Indriani

    2016-11-01

    Full Text Available Tetelo/Newcastle disease (ND inactive vaccine of genotipe VII virus local isolate have been developedin laboratory condition and compared with commercial ND vaccine. A total of 200 commercial layer chickenat 4 weeks age were divided into four groups, that were (1 vaccinated with ND genotype VII Indonesia/GTT/11, (2 vaccinated with commercial ND vaccine genotype VII, (3 vaccinated with commercial genotypeVI and (4 unvaccinated as control group. After two weeks post vaccination, 10 chicken from each groupwere sellected randomly and challenged with 105 EID50 per 0,1 mL of ND virus genotype VII Indonesian/GTT/11 by intramuscular. Chicken were observed, and swab were collected from oropharyngeal and cloacaat 2, 5, 7, 12 and 14 days post challenge. The result of this study showed inactived vaccine genotype VIIIndonesia/GTT/11 can induced a good antibody titer response to vaccinated chicken with mean titer 7.30log2 and CI 6.3 to 7.8, while commercial ND vaccine genotipe VII was 5.30 log2 with CI 3.8-6.7, andcommercial genotype VI was 4.8 log2 with CI 4.1-5.4. The level of protection which determined by noclinical signs, mortality and viral shedding showed 100% protection in chicken vaccinated with Indonesia/GTT/11 and commercial genotype VII were 100%, compared with control chicken, and vaccined commercialND vaccine genotype VII, compared with control chicken. While in chicken vaccinated commercial NDvaccine genotype VI showed viral shedding on day two post challenge, but there were no clinical sign andmortality. Based on this results, Indonesia/GTT/11 genotype VII ND vaccine could be used as an alternativeND vaccine to protect chicken from infection of ND virus genotype VII in the field.

  16. Cold-Chain Adaptability During Introduction of Inactivated Polio Vaccine in Bangladesh, 2015.

    Science.gov (United States)

    Billah, Mallick M; Zaman, K; Estivariz, Concepcion F; Snider, Cynthia J; Anand, Abhijeet; Hampton, Lee M; Bari, Tajul I A; Russell, Kevin L; Chai, Shua J

    2017-07-01

    Introduction of inactivated polio vaccine creates challenges in maintaining the cold chain for vaccine storage and distribution. We evaluated the cold chain in 23 health facilities and 36 outreach vaccination sessions in 8 districts and cities of Bangladesh, using purposive sampling during August-October 2015. We interviewed immunization and cold-chain staff, assessed equipment, and recorded temperatures during vaccine storage and transportation. All health facilities had functioning refrigerators, and 96% had freezers. Temperature monitors were observed in all refrigerators and freezers but in only 14 of 66 vaccine transporters (21%). Recorders detected temperatures >8°C for >60 minutes in 5 of 23 refrigerators (22%), 3 of 6 cold boxes (50%) transporting vaccines from national to subnational depots, and 8 of 48 vaccine carriers (17%) used in outreach vaccination sites. Temperatures cold boxes (21%) transporting vaccine from subnational depots to health facilities and 14 of 48 vaccine carriers (29%). Bangladesh has substantial cold-chain storage and transportation capacity after inactivated polio vaccine introduction, but temperature fluctuations during vaccine transport could cause vaccine potency loss that could go undetected. Bangladesh and other countries should strive to ensure consistent and sufficient cold-chain storage and monitor the cold chain during vaccine transportation at all levels. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

  17. 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,

  18. Rapid Engineering of Foot-and-Mouth Disease Vaccine and Challenge Viruses.

    Science.gov (United States)

    Lee, Seo-Yong; Lee, Yeo-Joo; Kim, Rae-Hyung; Park, Jeong-Nam; Park, Min-Eun; Ko, Mi-Kyeong; Choi, Joo-Hyung; Chu, Jia-Qi; Lee, Kwang-Nyeong; Kim, Su-Mi; Tark, Dongseob; Lee, Hyang-Sim; Ko, Young-Joon; Seo, Min-Goo; Park, Jung-Won; Kim, Byounghan; Lee, Myoung-Heon; Lee, Jong-Soo; Park, Jong-Hyeon

    2017-08-15

    There are seven antigenically distinct serotypes of foot-and-mouth disease virus (FMDV), each of which has intratypic variants. In the present study, we have developed methods to efficiently generate promising vaccines against seven serotypes or subtypes. The capsid-encoding gene (P1) of the vaccine strain O1/Manisa/Turkey/69 was replaced with the amplified or synthetic genes from the O, A, Asia1, C, SAT1, SAT2, and SAT3 serotypes. Viruses of the seven serotype were rescued successfully. Each chimeric FMDV with a replacement of P1 showed serotype-specific antigenicity and varied in terms of pathogenesis in pigs and mice. Vaccination of pigs with an experimental trivalent vaccine containing the inactivated recombinants based on the main serotypes O, A, and Asia1 effectively protected them from virus challenge. This technology could be a potential strategy for a customized vaccine with challenge tools to protect against epizootic disease caused by specific serotypes or subtypes of FMDV. IMPORTANCE Foot-and-mouth disease (FMD) virus (FMDV) causes significant economic losses. For vaccine preparation, the selection of vaccine strains was complicated by high antigenic variation. In the present study, we suggested an effective strategy to rapidly prepare and evaluate mass-produced customized vaccines against epidemic strains. The P1 gene encoding the structural proteins of the well-known vaccine virus was replaced by the synthetic or amplified genes of viruses of seven representative serotypes. These chimeric viruses generally replicated readily in cell culture and had a particle size similar to that of the original vaccine strain. Their antigenicity mirrored that of the original serotype from which their P1 gene was derived. Animal infection experiments revealed that the recombinants varied in terms of pathogenicity. This strategy will be a useful tool for rapidly generating customized FMD vaccines or challenge viruses for all serotypes, especially for FMD-free countries

  19. DENGUE VACCINES.

    Science.gov (United States)

    Thisyakorn, Usa; Thisyakorn, Chule

    2015-01-01

    The uniqueness of the dengue viruses (DENVs) and the spectrum of disease resulting from infection have made dengue vaccine development difficult. Several vaccine candidates are currently being evaluated in clinical studies. The candidate currently at the most advanced clinical development stage, a live-attenuated tetravalent vaccine based on the chimeric yellow fever-dengue virus (CYD-TDV), has progressed to Phase 3 efficacy studies. Several other live-attenuated vaccines, as well as subunit, DNA, and purified inactivated vaccine candidates are at earlier stages of clinical development. Additional technological approaches, such as virus-vectored and Virus-Like Particles (VLP)-based vaccines are under evaluation in preclinical studies.

  20. Green propolis phenolic compounds act as vaccine adjuvants, improving humoral and cellular responses in mice inoculated with inactivated vaccines

    OpenAIRE

    Fischer, Geferson; Paulino, Niraldo; Ribeiro, Maria Cristina Marcucci; Siedler, Bianca Sica; Munhoz, Lívia Silveira; Finger, Paula Fonseca; Vargas, Gilberto D`Avila; Hübner, Sílvia de Oliveira; Vidor, Telmo; Roehe, Paulo Michel

    2009-01-01

    Adjuvants play an important role in vaccine formulations by increasing their immunogenicity. In this study, the phenolic compound-rich J fraction (JFR) of a Brazilian green propolis methanolic extract stimulated cellular and humoral immune responses when co-administered with an inactivated vaccine against swine herpesvirus type 1 (SuHV-1). When compared to control vaccines that used aluminium hydroxide as an adjuvant, the use of 10 mg/dose of JFR significantly increased (p < 0.05) neutralizin...

  1. 9 CFR 113.205 - Newcastle Disease Vaccine, Killed Virus.

    Science.gov (United States)

    2010-01-01

    ... Virus. 113.205 Section 113.205 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.205 Newcastle Disease Vaccine, Killed Virus. Newcastle Disease Vaccine...

  2. 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.

  3. Antibody Persistence in Adults Two Years after Vaccination with an H1N1 2009 Pandemic Influenza Virus-Like Particle Vaccine.

    Directory of Open Access Journals (Sweden)

    Nuriban Valero-Pacheco

    Full Text Available The influenza virus is a human pathogen that causes epidemics every year, as well as potential pandemic outbreaks, as occurred in 2009. Vaccination has proven to be sufficient in the prevention and containment of viral spreading. In addition to the current egg-based vaccines, new and promising vaccine platforms, such as cell culture-derived vaccines that include virus-like particles (VLPs, have been developed. VLPs have been shown to be both safe and immunogenic against influenza infections. Although antibody persistence has been studied in traditional egg-based influenza vaccines, studies on antibody response durations induced by VLP influenza vaccines in humans are scarce. Here, we show that subjects vaccinated with an insect cell-derived VLP vaccine, in the midst of the 2009 H1N1 influenza pandemic outbreak in Mexico City, showed antibody persistence up to 24 months post-vaccination. Additionally, we found that subjects that reported being revaccinated with a subsequent inactivated influenza virus vaccine showed higher antibody titres to the pandemic influenza virus than those who were not revaccinated. These findings provide insights into the duration of the antibody responses elicited by an insect cell-derived pandemic influenza VLP vaccine and the possible effects of subsequent influenza vaccination on antibody persistence induced by this VLP vaccine in humans.

  4. Antibody Persistence in Adults Two Years after Vaccination with an H1N1 2009 Pandemic Influenza Virus-Like Particle Vaccine.

    Science.gov (United States)

    Valero-Pacheco, Nuriban; Pérez-Toledo, Marisol; Villasís-Keever, Miguel Ángel; Núñez-Valencia, Adriana; Boscó-Gárate, Ilka; Lozano-Dubernard, Bernardo; Lara-Puente, Horacio; Espitia, Clara; Alpuche-Aranda, Celia; Bonifaz, Laura C; Arriaga-Pizano, Lourdes; Pastelin-Palacios, Rodolfo; Isibasi, Armando; López-Macías, Constantino

    2016-01-01

    The influenza virus is a human pathogen that causes epidemics every year, as well as potential pandemic outbreaks, as occurred in 2009. Vaccination has proven to be sufficient in the prevention and containment of viral spreading. In addition to the current egg-based vaccines, new and promising vaccine platforms, such as cell culture-derived vaccines that include virus-like particles (VLPs), have been developed. VLPs have been shown to be both safe and immunogenic against influenza infections. Although antibody persistence has been studied in traditional egg-based influenza vaccines, studies on antibody response durations induced by VLP influenza vaccines in humans are scarce. Here, we show that subjects vaccinated with an insect cell-derived VLP vaccine, in the midst of the 2009 H1N1 influenza pandemic outbreak in Mexico City, showed antibody persistence up to 24 months post-vaccination. Additionally, we found that subjects that reported being revaccinated with a subsequent inactivated influenza virus vaccine showed higher antibody titres to the pandemic influenza virus than those who were not revaccinated. These findings provide insights into the duration of the antibody responses elicited by an insect cell-derived pandemic influenza VLP vaccine and the possible effects of subsequent influenza vaccination on antibody persistence induced by this VLP vaccine in humans.

  5. An open, prospective, randomized study comparing the immunogenicity and safety of two inactivated hepatitis A pediatric vaccines in toddlers, children and adolescents in China.

    Science.gov (United States)

    Li, Rong Cheng; Li, Yanping; Yi, Nong; Huang, Lirong; Wan, Zongju; Zhang, Yanping; Rasuli, Anvar

    2013-02-01

    Vaccines against hepatitis A provide long-lasting protection in both adults and children. The aim of this study was to demonstrate that the inactivated hepatitis A vaccine AVAXIM 80U Pediatric is safe and not inferior in terms of seroprotection rate to HAVRIX 720 vaccine 1 month after booster vaccination. An open, randomized, single-center trial was conducted in China in healthy antihepatitis A virus seronegative individuals from 12 months to 15 years of age. Participants were randomized in a 2:1 ratio to receive either AVAXIM 80U Pediatric or HAVRIX 720, followed by a booster vaccination, using the same vaccine 6 months afterward. A total of 720 individuals were included in the study, 480 in the AVAXIM 80U Pediatric group and 240 in the HAVRIX 720 group, and 686 individuals completed the full vaccination schedule. AVAXIM 80U Pediatric was statistically noninferior to HAVRIX 720 in terms of seroprotection rate for all individuals and in each of 3 age groups: toddlers (12-23 months), children (2-11 years) and adolescents (12-15 years). Antihepatitis A virus geometric mean titers were significantly higher with AVAXIM 80U Pediatric than with HAVRIX 720. Both inactivated hepatitis A vaccines were well-tolerated and had a similar incidence and type of adverse events. AVAXIM 80U Pediatric is safe and immunogenic, with a seroprotection rate that is not inferior to HAVRIX 720 in a pediatric population of healthy individuals.

  6. Recent advances in the development of vaccines for Ebola virus disease.

    Science.gov (United States)

    Ohimain, Elijah Ige

    2016-01-04

    Ebola virus is one of the most dangerous microorganisms in the world causing hemorrhagic fevers in humans and non-human primates. Ebola virus (EBOV) is a zoonotic infection, which emerges and re-emerges in human populations. The 2014 outbreak was caused by the Zaire strain, which has a kill rate of up to 90%, though 40% was recorded in the current outbreak. The 2014 outbreak is larger than all 20 outbreaks that have occurred since 1976, when the virus was first discovered. It is the first time that the virus was sustained in urban centers and spread beyond Africa into Europe and USA. Thus far, over 22,000 cases have been reported with about 50% mortality in one year. There are currently no approved therapeutics and preventive vaccines against Ebola virus disease (EVD). Responding to the devastating effe1cts of the 2014 outbreak and the potential risk of global spread, has spurred research for the development of therapeutics and vaccines. This review is therefore aimed at presenting the progress of vaccine development. Results showed that conventional inactivated vaccines produced from EBOV by heat, formalin or gamma irradiation appear to be ineffective. However, novel vaccines production techniques have emerged leading to the production of candidate vaccines that have been demonstrated to be effective in preclinical trials using small animal and non-human primates (NHP) models. Some of the promising vaccines have undergone phase 1 clinical trials, which demonstrated their safety and immunogenicity. Many of the candidate vaccines are vector based such as Vesicular Stomatitis Virus (VSV), Rabies Virus (RABV), Adenovirus (Ad), Modified Vaccinia Ankara (MVA), Cytomegalovirus (CMV), human parainfluenza virus type 3 (HPIV3) and Venezuelan Equine Encephalitis Virus (VEEV). Other platforms include virus like particle (VLP), DNA and subunit vaccines. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. 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.

  8. Inactivation of porcine epidemic diarrhea virus using heated water

    Directory of Open Access Journals (Sweden)

    Michele M. Zentkovich

    2016-12-01

    Full Text Available Porcine epidemic diarrhea virus (PEDV is a very contagious swine pathogen that spreads easily via the fecal-oral route, notably from contaminated fomites. The present study investigated heated water as a method for rapid thermal inactivation of PEDV. Cell-culture adapted PEDV was treated with water at varying temperatures and viral titers were measured at multiple time points post-treatment. Viable PEDV was not recovered after a ten second or longer treatment with water heated to ≥76 °C; however, PEDV nucleic acid was detected in all samples regardless of treatment. Hot water decontamination could be considered in settings where chemical disinfection is impractical.

  9. IPV v2.0 : upgrading the established inactivated polio vaccine production process

    NARCIS (Netherlands)

    Thomassen, Y.E.

    2014-01-01

    The first vaccine against poliovirus (PV), the causative agent of poliomyelitis, was developed in the 1950s by Jonas Salk. The vaccine (IPV) consists of an injected dose of purified and inactivated wild-type PVs (all three serotypes). Soon after this discovery, at the Rijks Instituut voor de

  10. IPV v2.0 : upgrading the established inactivated polio vaccine production process

    NARCIS (Netherlands)

    Thomassen, Y.E.

    2014-01-01

    The first vaccine against poliovirus (PV), the causative agent of poliomyelitis, was developed in the 1950s by Jonas Salk. The vaccine (IPV) consists of an injected dose of purified and inactivated wild-type PVs (all three serotypes). Soon after this discovery, at the Rijks Instituut voor de

  11. Gold nanorod vaccine for respiratory syncytial virus

    International Nuclear Information System (INIS)

    Stone, John W; Thornburg, Natalie J; Blum, David L; Kuhn, Sam J; Crowe Jr, James E; Wright, David W

    2013-01-01

    Respiratory syncytial virus (RSV) is a major cause of pneumonia and wheezing in infants and the elderly, but to date there is no licensed vaccine. We developed a gold nanorod construct that displayed the major protective antigen of the virus, the fusion protein (F). Nanorods conjugated to RSV F were formulated as a candidate vaccine preparation by covalent attachment of viral protein using a layer-by-layer approach. In vitro studies using ELISA, electron microscopy and circular dichroism revealed that conformation-dependent epitopes were maintained during conjugation, and transmission electron microscopy studies showed that a dispersed population of particles could be achieved. Human dendritic cells treated with the vaccine induced immune responses in primary human T cells. These results suggest that this vaccine approach may be a potent method for immunizing against viruses such as RSV with surface glycoproteins that are targets for the human immune response. (paper)

  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. Development of methods to measure virus inactivation in fresh waters.

    Science.gov (United States)

    Ward, R L; Winston, P E

    1985-11-01

    This study concerns the identification and correction of deficiencies in methods used to measure inactivation rates of enteric viruses seeded into environmental waters. It was found that viable microorganisms in an environmental water sample increased greatly after addition of small amounts of nutrients normally present in the unpurified seed virus preparation. This burst of microbial growth was not observed after seeding the water with purified virus. The use of radioactively labeled poliovirus revealed that high percentages of virus particles, sometimes greater than 99%, were lost through adherence to containers, especially in less turbid waters. This effect was partially overcome by the use of polypropylene containers and by the absence of movement during incubation. Adherence to containers clearly demonstrated the need for labeled viruses to monitor losses in this type of study. Loss of viral infectivity in samples found to occur during freezing was avoided by addition of broth. Finally, microbial contamination of the cell cultures during infectivity assays was overcome by the use of gentamicin and increased concentrations of penicillin, streptomycin, and amphotericin B.

  14. Influence of pH, Salt and Temperature on Pressure Inactivation of Hepatitis A virus

    Science.gov (United States)

    The effects of pH (3-7), NaCl (0-6%), and temperature on pressure inactivation of hepatitis A virus (HAV) were determined. The HAV samples were treated at 400 MPa for 1 min at 5, 20, and 50C. Decreasing solution pH enhanced pressure inactivation of HAV. This enhanced inactivation effect was most e...

  15. A cDNA Clone-Launched Platform for High-Yield Production of Inactivated Zika Vaccine

    Directory of Open Access Journals (Sweden)

    Yujiao Yang

    2017-03-01

    Full Text Available A purified inactivated vaccine (PIV using the Zika virus (ZIKV Puerto Rico strain PRVABC59 showed efficacy in monkeys, and is currently in a phase I clinical trial. High-yield manufacture of this PIV is essential for its development and vaccine access. Here we report an infectious cDNA clone-launched platform to maximize its yield. A single NS1 protein substitution (K265E was identified to increase ZIKV replication on Vero cells (a cell line approved for vaccine production for both Cambodian FSS13025 and Puerto Rico PRVABC59 strains. The NS1 mutation did not affect viral RNA synthesis, but significantly increased virion assembly through an increased interaction between NS1 and NS2A (a known regulator of flavivirus assembly. The NS1 mutant virus retained wild-type virulence in the A129 mouse model, but decreased its competence to infect Aedes aegypti mosquitoes. To further increase virus yield, we constructed an infectious cDNA clone of the clinical trial PIV strain PRVABC59 containing three viral replication-enhancing mutations (NS1 K265E, prM H83R, and NS3 S356F. The mutant cDNA clone produced >25-fold more ZIKV than the wild-type parent on Vero cells. This cDNA clone-launched manufacture platform has the advantages of higher virus yield, shortened manufacture time, and minimized chance of contamination.

  16. Duration of antibody response following vaccination against feline immunodeficiency virus.

    Science.gov (United States)

    Westman, Mark E; Malik, Richard; Hall, Evelyn; Harris, Matthew; Hosie, Margaret J; Norris, Jacqueline M

    2017-10-01

    Objectives Recently, two point-of-care (PoC) feline immunodeficiency virus (FIV) antibody test kits (Witness and Anigen Rapid) were reported as being able to differentiate FIV-vaccinated from FIV-infected cats at a single time point, irrespective of the gap between testing and last vaccination (0-7 years). The aim of the current study was to investigate systematically anti-FIV antibody production over time in response to the recommended primary FIV vaccination series. Methods First, residual plasma from the original study was tested using a laboratory-based ELISA to determine whether negative results with PoC testing were due to reduced as opposed to absent antibodies to gp40. Second, a prospective study was performed using immunologically naive client-owned kittens and cats given a primary FIV vaccination series using a commercially available inactivated whole cell/inactivated whole virus vaccine (Fel-O-Vax FIV, three subcutaneous injections at 4 week intervals) and tested systematically (up to 11 times) over 6 months, using four commercially available PoC FIV antibody kits (SNAP FIV/FeLV Combo [detects antibodies to p15/p24], Witness FeLV/FIV [gp40], Anigen Rapid FIV/FeLV [p24/gp40] and VetScan FeLV/FIV Rapid [p24]). Results The laboratory-based ELISA showed cats from the original study vaccinated within the previous 0-15 months had detectable levels of antibodies to gp40, despite testing negative with two kits that use gp40 as a capture antigen (Witness and Anigen Rapid kits). The prospective study showed that antibody testing with SNAP Combo and VetScan Rapid was positive in all cats 2 weeks after the second primary FIV vaccination, and remained positive for the duration of the study (12/12 and 10/12 cats positive, respectively). Antibody testing with Witness and Anigen Rapid was also positive in a high proportion of cats 2 weeks after the second primary FIV vaccination (8/12 and 7/12, respectively), but antibody levels declined below the level of detection in

  17. The inactivation of hepatitis A virus and other model viruses by UV irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Battigelli, D.A.; Sobsey, M.D.; Lobe, D.C. (North Carolina Univ., Chapel Hill, NC (United States). Dept. of Environmental Sciences)

    1993-01-01

    Ultraviolet light is an attractive alternative to chemical disinfection of water, but little is known about its ability to inactivate important waterborne pathogens such as hepatitis A virus. Therefore, the sensitivity of HAV strain HM-175, coxsackievirus type B-5, rotavirus strain SA-11, and bacteriophages MS2 and [phi]X174 to ultraviolet radiation of 254 nm wavelength in phosphate buffered water was determined. Purified stocks of the viruses were combined and exposed to collimated UV radiation in a stirred reactor for a total dose of up to 40 mW sec/cm[sup 2]. Virus survival kinetics were determined from samples removed at dose intervals. The results of these experiments indicate that UV radiation can effectively inactivate viruses of public health concern in drinking water. (author).

  18. Does a monovalent inactivated human rotavirus vaccine induce heterotypic immunity? Evidence from animal studies.

    Science.gov (United States)

    Jiang, Baoming; Wang, Yuhuan; Glass, Roger I

    2013-08-01

    There is substantial evidence for broad cross-reactive immunity and heterotypic protection among human rotavirus strains in children with natural infection or with monovalent Rotarix vaccination. In this commentary, we addressed this same topic by testing sera of guinea pigs and gnotobiotic piglets that were intramuscularly immunized with an inactivated human rotavirus vaccine and also demonstrated a broad cross-protective immunity among human rotavirus strains. Our findings from a single human strain in animal studies bode well for a low cost and efficacious inactivated vaccine to protect children against rotavirus disease throughout the world.

  19. Virus-like-vaccines against HIV

    DEFF Research Database (Denmark)

    Andersson, Anne Marie C.; Schwerdtfeger, Melanie; Holst, Peter J.

    2018-01-01

    Protection against chronic infections has necessitated the development of ever-more potent vaccination tools. HIV seems to be the most challenging foe, with a remarkable, poorly immunogenic and fragile surface glycoprotein and the ability to overpower the cell immune system. Virus-like-particle (......Protection against chronic infections has necessitated the development of ever-more potent vaccination tools. HIV seems to be the most challenging foe, with a remarkable, poorly immunogenic and fragile surface glycoprotein and the ability to overpower the cell immune system. Virus...... of HIV. Such vaccines are immunologically perceived as viruses, as they infect cells and produce VLPs in situ, but they only resemble viruses, as the replication defective vectors and VLPs cannot propagate an infection. The inherent safety of such a platform, despite robust particle production...

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

    Directory of Open Access Journals (Sweden)

    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.

  1. 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.

  2. Antibody quality and protection from lethal Ebola virus challenge in nonhuman primates immunized with rabies virus based bivalent vaccine.

    Directory of Open Access Journals (Sweden)

    Joseph E Blaney

    Full Text Available We have previously described the generation of a novel Ebola virus (EBOV vaccine platform based on (a replication-competent rabies virus (RABV, (b replication-deficient RABV, or (c chemically inactivated RABV expressing EBOV glycoprotein (GP. Mouse studies demonstrated safety, immunogenicity, and protective efficacy of these live or inactivated RABV/EBOV vaccines. Here, we evaluated these vaccines in nonhuman primates. Our results indicate that all three vaccines do induce potent immune responses against both RABV and EBOV, while the protection of immunized animals against EBOV was largely dependent on the quality of humoral immune response against EBOV GP. We also determined if the induced antibodies against EBOV GP differ in their target, affinity, or the isotype. Our results show that IgG1-biased humoral responses as well as high levels of GP-specific antibodies were beneficial for the control of EBOV infection after immunization. These results further support the concept that a successful EBOV vaccine needs to induce strong antibodies against EBOV. We also showed that a dual vaccine against RABV and filoviruses is achievable; therefore addressing concerns for the marketability of this urgently needed vaccine.

  3. EDQM biological reference preparation for rabies vaccine (inactivated) for veterinary use.

    Science.gov (United States)

    Daas, A; Bruckner, L; Milne, C

    2015-01-01

    Rabies is a deadly zoonotic disease. Control of rabies in animals by vaccination is an important strategy to protect humans from infection and control the spread of the disease. Requirements for the quality control of rabies vaccines (inactivated) for veterinary use include an in vivo quantitative potency determination as outlined in the Ph. Eur. monograph 0451. Performance of this assay requires a reference preparation calibrated in International Units (IU). A European Pharmacopeia (Ph. Eur.) Biological Reference Preparation (BRP) for rabies vaccines (inactivated) for veterinary use, calibrated in IU, has been established for this purpose. Due to the dwindling stocks of the current batch (batch 4) of Ph. Eur. BRP for rabies vaccines (inactivated) for veterinary use, a collaborative study was run as part of the EDQM Biological Standardisation Programme to establish BRP batch 5. Ten laboratories, including Official Medicines Control Laboratories and manufacturers, participated. The candidate BRP5 was assayed against the 6(th) International Standard for rabies vaccine using the in vivo vaccination-challenge assay (monograph 0451) to assign a potency value. The candidate was also compared to BRP batch 4 to establish continuity. Taking into account the results from the comparisons a potency of 10 IU/vial was assigned and in March 2015 the Ph. Eur. Commission adopted the material as Ph. Eur. BRP for rabies vaccines (inactivated) for veterinary use batch 5. In addition to the in vivo assay 3 laboratories tested the candidate material using their in-house in vitro assays for information.

  4. Virus-Like-Vaccines against HIV.

    Science.gov (United States)

    Andersson, Anne-Marie C; Schwerdtfeger, Melanie; Holst, Peter J

    2018-02-11

    Protection against chronic infections has necessitated the development of ever-more potent vaccination tools. HIV seems to be the most challenging foe, with a remarkable, poorly immunogenic and fragile surface glycoprotein and the ability to overpower the cell immune system. Virus-like-particle (VLP) vaccines have emerged as potent inducers of antibody and helper T cell responses, while replication-deficient viral vectors have yielded potent cytotoxic T cell responses. Here, we review the emerging concept of merging these two technologies into virus-like-vaccines (VLVs) for the targeting of HIV. Such vaccines are immunologically perceived as viruses, as they infect cells and produce VLPs in situ, but they only resemble viruses, as the replication defective vectors and VLPs cannot propagate an infection. The inherent safety of such a platform, despite robust particle production, is a distinct advantage over live-attenuated vaccines that must balance safety and immunogenicity. Previous studies have delivered VLVs encoded in modified Vaccinia Ankara vectors and we have developed the concept into a single-reading adenovirus-based technology capable of eliciting robust CD8⁺ and CD4⁺ T cells responses and trimer binding antibody responses. Such vaccines offer the potential to display the naturally produced immunogen directly and induce an integrated humoral and cellular immune response.

  5. Super-oxidized water inactivates major viruses circulating in swine farms.

    Science.gov (United States)

    Chen, Jianing; Zhang, Chengyu; Liu, Yue; Liu, Guangliang

    2017-04-01

    Disinfectant is commonly employed to eliminate infectious agents and prevent its transmission. In this study, we investigated the efficacy of Medilox ® super-oxidized water on inactivating veterinary viruses mainly circulating in swine farms. The results demonstrated that this super-oxidized water could effectively inactivate porcine viruses. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Evaluation of the thermotolerance of an inactivated rabies vaccine ...

    African Journals Online (AJOL)

    This study provides the first robust data that the antibody response of dogs vaccinated with Nobivac® Rabies vaccine stored for several months at high temperatures (up to 30 °C) is not inferior to that of dogs vaccinated with vaccine stored under recommended cold-chain conditions (2 - 8 °C). A controlled and randomized ...

  7. [Vaccines against varicella-zoster virus (VZV)].

    Science.gov (United States)

    Salleras, Luis; Salleras, Montserrat; Soldevila, Nuria; Prat, Andreu; Garrido, Patricio; Domínguez, Ángela

    2015-01-01

    In Western countries, two attenuated varicella vaccines derived from the OKA strain are licensed: Varilrix® GlaxoSmithKline (OKA/RIT strain) and Varivax® Merck Sharp and Dohme (OKA/Merck strain). Currently, in Spain, varicella vaccination is only included in the Ministry of Health, Social Services and Equality official vaccination calendar for administration in adolescents who have not had the disease. Given the good results obtained in Navarra and Madrid with universal administration of the vaccine in children, it would be desirable to include the vaccine in the routine immunization schedule, with the administration of two doses at 15-18 months of age in the future. The protective efficacy of the attenuated herpes zoster vaccine was evaluated in the Shingles Prevention Study, which showed that in the short term (0-4 years) the vaccine reduced the incidence of herpes zoster by 53%, post-herpetic neuralgia by 66%, and the disease burden in immunocompetent persons aged ≥60 years by 61%. Another study demonstrated protective efficacy in persons aged 50-59 years. Over time, the protective efficacy decreases, but remains at acceptable levels, especially for post-herpetic neuralgia and the disease burden. Recently, the results of a controlled clinical trial (phase III) conducted in 18 countries to assess the protective efficacy of the inactivated subunit vaccine (glycoprotein E) adjuvanted with the adjuvant AS01B were published. The study inferred that the vaccine significantly reduced the incidence of herpes zoster in the short term (3.2 years) in people aged ≥50 years. Vaccine protection did not decrease with age at vaccination, ranging between 96.8% and 97.9% in all age groups. Copyright © 2015. Published by Elsevier España, S.L.U.

  8. Age affects quantity but not quality of antibody responses after vaccination with an inactivated flavivirus vaccine against tick-borne encephalitis.

    Directory of Open Access Journals (Sweden)

    Karin Stiasny

    Full Text Available The impairment of immune functions in the elderly (immunosenescence results in post-vaccination antibody titers that are significantly lower than in young individuals. It is, however, a controversial question whether also the quality of antibodies declines with age. In this study, we have therefore investigated the age-dependence of functional characteristics of antibody responses induced by vaccination with an inactivated flavivirus vaccine against tick-borne encephalitis (TBE. For this purpose, we quantified TBE virus-specific IgG and neutralizing antibody titers in post-vaccination sera from groups of young and elderly healthy adults and determined antibody avidities and NT/ELISA titer ratios (functional activity. In contrast to the quantitative impairment of antibody production in the elderly, we found no age-related differences in the avidity and functional activity of antibodies induced by vaccination, which also appeared to be independent of the age at primary immunization. There was no correlation between antibody avidity and NT/ELISA ratios suggesting that additional factors affect the quality of polyclonal responses, independent of age. Our work indicates that healthy elderly people are able to produce antibodies in response to vaccination with similar avidity and functional activity as young individuals, albeit at lower titers.

  9. Protection against dengue virus by non-replicating and live attenuated vaccines used together in a prime boost vaccination strategy.

    Science.gov (United States)

    Simmons, Monika; Burgess, Timothy; Lynch, Julia; Putnak, Robert

    2010-01-20

    A new vaccination strategy for dengue virus (DENV) was evaluated in rhesus macaques by priming with tetravalent purified inactivated virus (TPIV) or tetravalent plasmid DNA vaccines expressing the structural prME gene region (TDNA) then boosting 2 months later with a tetravalent live attenuated virus (TLAV) vaccine. Both vaccine combinations elicited virus neutralizing (N) antibodies. The TPIV/TLAV combination afforded complete protection against DENV 3 challenge at month 8. In a second experiment, priming with TPIV elicited N antibodies against all four serotypes (GMT 1:28 to 1:43). Boosting with TLAV led to an increase in the GMT for each serotype (1:500 to 1:1200 for DENVs 1, 3, and 4, and greater than 1:6000 for DENV 2), which declined by month 8 (GMT 1:62 for DENV 3, 1:154 for DENV 1, 1:174 for DENV 4, and 1:767 for DENV 2). After challenge with each one of the four DENV serotypes, vaccinated animals exhibited no viremia but showed anamnestic antibody responses to the challenge viruses.

  10. Progression of rabbit haemorrhagic disease virus 2 upon vaccination in an industrial rabbitry: a laboratorial approach

    OpenAIRE

    C.L. Carvalho; E.L. Duarte; J.M. Monteiro; C. Afonso; J. Pacheco; P. Carvalho; P. Mendonça; A. Botelho; T. Albuquerque; P. Themudo; M. Fevereiro; A.M. Henriques; S.S. Santos Barros; M. Dias Duarte

    2017-01-01

    Rabbit haemorrhagic disease virus 2 (RHDV2) emerged recently in several European countries, leading to extensive economic losses in the industry. In response to this new infection, specific inactivated vaccines were developed in Europe and full and rapid setup of protective immunity induced by vaccination was reported. However, data on the efficacy of these vaccines in an ongoing-infection scenario is unavailable. In this study we investigated an infected RHDV2 indoor industrial meat rabbitry...

  11. 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.

  12. 9 CFR 113.214 - Parvovirus Vaccine, Killed Virus (Canine).

    Science.gov (United States)

    2010-01-01

    ... (Canine). 113.214 Section 113.214 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... REQUIREMENTS Killed Virus Vaccines § 113.214 Parvovirus Vaccine, Killed Virus (Canine). Parvovirus Vaccine... antibody against canine parvovirus to determine susceptibility. A constant virus-varying serum...

  13. Effect of receptor binding specificity on the immunogenicity and protective efficacy of influenza virus A H1 vaccines

    Science.gov (United States)

    Sun, Xiangjie; Cao, Weiping; Pappas, Claudia; Liu, Feng; Katz, Jacqueline M.; Tumpey, Terrence M.

    2018-01-01

    The biological basis for the poor immunogenicity of unadjuvanted avian influenza A virus vaccines in mammals is not well understood. Here, we mutated the hemagglutinin (HA) of two H1N1 virus vaccines to determine whether virus receptor binding specificity contributes to the low immunogenicity of avian influenza virus vaccines. Mutations were introduced into the HA of an avian influenza virus, A/Duck/New York/15024–21/96 (Dk/96) which switched the binding preference from α2,3- to α2,6-linked sialic acid (SA). A switch in receptor specificity of the human A/South Carolina/1/18 (SC/18) virus generated a mutant virus with α2,3 SA (avian) binding preference. Inactivated vaccines were generated and administered to mice and ferrets intramuscularly. We found that the vaccines with human receptor binding preference induced slightly higher antibody titers and cell-mediated immune responses compared to their isogenic viruses with avian receptor binding specificity. Upon challenge with DK/96 or SC18 virus, differences in lung virus titers between the vaccine groups with different receptor-binding specificities were minimal. Overall, our data suggest that receptor binding specificity contributes only marginally to the immunogenicity of avian influenza vaccines and that other factors may also be involved. PMID:25078114

  14. Nucleic acid-based vaccines targeting respiratory syncytial virus: Delivering the goods.

    Science.gov (United States)

    Smith, Trevor R F; Schultheis, Katherine; Broderick, Kate E

    2017-11-02

    Respiratory syncytial virus (RSV) is a massive medical burden on a global scale. Infants, children and the elderly represent the vulnerable populations. Currently there is no approved vaccine to protect against the disease. Vaccine development has been hindered by several factors including vaccine enhanced disease (VED) associated with formalin-inactivated RSV vaccines, inability of target populations to raise protective immune responses after vaccination or natural viral infection, and a lack of consensus concerning the most appropriate virus-associated target antigen. However, with recent advances in the molecular understanding of the virus, and design of highly characterized vaccines with enhanced immunogenicity there is new belief a RSV vaccine is possible. One promising approach is nucleic acid-based vaccinology. Both DNA and mRNA RSV vaccines are showing promising results in clinically relevant animal models, supporting their transition into humans. Here we will discuss this strategy to target RSV, and the ongoing studies to advance the nucleic acid vaccine platform as a viable option to protect vulnerable populations from this important disease.

  15. Application of solid-phase radioimmunoassay in determining antibodies to Aujeszky's disease virus in blood serum of vaccinated pigs

    International Nuclear Information System (INIS)

    Rodak, L.; Smid, B.; Valicek, L.

    1983-01-01

    In the blood sera of pigs vaccinated with inactivated vaccines manufactured by three different manufacturers the RIA method was used to determine the specific antibodies to the virus of Aujeszky's disease. In certain groups of vaccinated pigs the results of the RIA examination are unfavourably affected by the bond of antibodies to the cellular antigenous determinants. This proves that following vaccination antibodies are formed not only against the viral antigen but also against the antigens of cells on which the vaccination virus is propagated. These shortcomings are eliminated by the use of suitable cellular cultures for the preparation of viral and control antigens. Antigens are applicable for RIA and for ELISA examinations of blood sera of infected and vaccinated pigs. The advantages are described of the RIA and ELISA methods as compared with the virus neutralization test. (author)

  16. Depression of Vaccinal Immunity to Marek's Disease by Infection with Chicken Infectious Anemia Virus.

    Science.gov (United States)

    Zhang, Yankun; Cui, Ning; Han, Ni; Wu, Jiayan; Cui, Zhizhong; Su, Shuai

    2017-01-01

    Marek's disease (MD) has been occurring with increasing frequency in chickens in recent years. To our knowledge, however, there has been no report of the very virulent plus (vv+) MD virus (MDV) field isolate in China. Studies have shown that dual infection with immunosuppressive viruses such as chicken infectious anemia virus (CIAV) occurs frequently in chickens developing MD. In this study, we performed a designed set of in vivo experiments, which comprised five different groups of chickens, including the group of CVI988/Rispens-vaccinated chickens, the groups of CVI988/Rispens-vaccinated chickens infected with MDV or CIAV or both viruses (MDV and CIAV), and the group of MDV-challenged chickens. The effects of CIAV dual infection on the immunization of commercial MDV vaccine CVI988/Rispens were evaluated. The results show that infection of the SD15 strain of CIAV significantly reduced the weight and antibody titers to avian influenza virus (AIV)/Newcastle disease virus (NDV) inactivated vaccines of chickens immunized with the CVI988/Rispens, and resulted in the atrophy of thymus/bursa and the enlargement of spleen. The CVI988/Rispens vaccination conferred good immune protection for chickens challenged with 2000 PFU of the GX0101 strain of MDV. However, dual infection with SD15 significantly reduced the body weight, antibody titers induced by AIV/NDV inactivated vaccines and protective index of CVI988/Rispens, and resulted in the aggravation of the immunosuppression, mortality, and viremia of GX0101 in CVI988/Rispens-immunized/GX0101-challenged chickens. Overall, CIAV infection significantly reduced the protective effects of the CVI988/Rispens vaccine against MDV, implying that concurrent infection with CIAV may be a major contributor in the frequent attacks of MD in China in recent years.

  17. Environmental Poliovirus Surveillance during Oral Poliovirus Vaccine and Inactivated Poliovirus Vaccine Use in Córdoba Province, Argentina▿

    OpenAIRE

    Mueller, Judith E.; Bessaud, Maël; Huang, Q. Sue; Martinez, Laura C.; Barril, Patricia A.; Morel, Viviane; Balanant, Jean; Bocacao, Judy; Hewitt, Joanne; Gessner, Brad D.; Delpeyroux, Francis; Nates, Silvia V.

    2009-01-01

    This study compares the presence of environmental poliovirus in two Argentinean populations using oral poliovirus vaccine (OPV) or inactivated poliovirus vaccine (IPV). From January 2003 to December 2005, Córdoba City used IPV in routine infant immunizations, with the exception of intermittent OPV use in August 2005. Between May 2005 and April 2006, we collected weekly wastewater samples in Córdoba City and the province's three major towns, which continued OPV use at all times. Wastewater sam...

  18. Thermotolerance of an inactivated rabies vaccine for dogs.

    Science.gov (United States)

    Lankester, Felix J; Wouters, Pieter A W M; Czupryna, Anna; Palmer, Guy H; Mzimbiri, Imam; Cleaveland, Sarah; Francis, Mike J; Sutton, David J; Sonnemans, Denny G P

    2016-11-04

    This study provides the first robust data that the antibody response of dogs vaccinated with Nobivac® Rabies vaccine stored for several months at high temperatures (up to 30°C) is not inferior to that of dogs vaccinated with vaccine stored under recommended cold-chain conditions (2-8°C). A controlled and randomized non-inferiority study was carried out comparing the four-week post vaccination serological responses of Tanzanian village dogs inoculated with vaccine which had been stored at elevated temperatures for different periods of time with those of dogs vaccinated with the same product stored according to label recommendations. Specifically, the neutralizing antibody response following the use of vaccine which had been stored for up to six months at 25°C or for three months at 30°C was not inferior to that following the use of cold-chain stored vaccine. These findings provide reassurance that the vaccine is likely to remain efficacious even if exposed to elevated temperatures for limited periods of time and, under these circumstances, it can safely be used and not necessarily destroyed or discarded. The availability of thermotolerant vaccines has been an important factor in the success of several disease control and elimination programs and could greatly increase the capacity of rabies vaccination campaigns to access hard to reach communities in Africa and Asia. We have not confirmed a 3-year duration of immunity for the high temperature stored vaccine, however because annual re-vaccination is usually practiced for dogs presented for vaccination during campaigns in Africa and Asia this should not be a cause for concern. These findings will provide confidence that, for rabies control and elimination programs using this vaccine in low-income settings, more flexible delivery models could be explored, including those that involve limited periods of transportation and storage at temperatures higher than that currently recommended. Copyright © 2016 The Authors

  19. Preparation and efficacy of a live newcastle disease virus vaccine encapsulated in chitosan nanoparticles.

    Directory of Open Access Journals (Sweden)

    Kai Zhao

    Full Text Available BACKGROUND: Newcastle disease (ND is a highly contagious viral disease of poultry caused by pathogenic strains of the Newcastle disease virus (NDV. Live NDV vaccines are administered by drinking water, eyedrops or coarse aerosol spray. To further enhance mucosal immune responses, chitosan nanoparticles were developed for the mucosal delivery of a live NDV vaccine. METHODOLOGY/PRINCIPAL FINDINGS: A lentogenic live-virus vaccine (strain LaSota against NDV encapsulated in chitosan nanoparticles were developed using an ionic crosslinking method. Chitosan nanoparticles containing the lentogenic live-virus vaccine against NDV (NDV-CS-NPs were produced with good morphology, high stability, a mean diameter of 371.1 nm, an encapsulation rate of 77% and a zeta potential of +2.84 mV. The Western blotting analysis showed that NDV structural proteins were detected in NDV-CS-NPs. The virus release assay results of NDV-CS-NPs indicated that NDV was released from NDV-CS-NPs. Chickens immunized orally or intranasally with NDV-CS-NPs were fully protected whereas one out of five chickens immunized with the LaSota live NDV vaccine and three out of five chickens immunized with the inactivated NDV vaccine were dead after challenge with the highly virulent NDV strain F48E9. CONCLUSIONS/SIGNIFICANCE: NDV-CS-NPs induced better protection of immunized specific pathogen free chickens compared to the live NDV vaccine strain LaSota and the inactivated NDV vaccine. This study lays a foundation for the further development of mucosal vaccines and drugs encapsulated in chitosan nanoparticles.

  20. Recombinant viruses as vaccines against viral diseases

    Directory of Open Access Journals (Sweden)

    A.P.D. Souza

    2005-04-01

    Full Text Available Vaccine approaches to infectious diseases are widely applied and appreciated. Amongst them, vectors based on recombinant viruses have shown great promise and play an important role in the development of new vaccines. Many viruses have been investigated for their ability to express proteins from foreign pathogens and induce specific immunological responses against these antigens in vivo. Generally, gene-based vaccines can stimulate potent humoral and cellular immune responses and viral vectors might be an effective strategy for both the delivery of antigen-encoding genes and the facilitation and enhancement of antigen presentation. In order to be utilized as a vaccine carrier, the ideal viral vector should be safe and enable efficient presentation of required pathogen-specific antigens to the immune system. It should also exhibit low intrinsic immunogenicity to allow for its re-administration in order to boost relevant specific immune responses. Furthermore, the vector system must meet criteria that enable its production on a large-scale basis. Several viral vaccine vectors have thus emerged to date, all of them having relative advantages and limits depending on the proposed application, and thus far none of them have proven to be ideal vaccine carriers. In this review we describe the potential, as well as some of the foreseeable obstacles associated with viral vaccine vectors and their use in preventive medicine.

  1. Effects of UVA irradiation, aryl azides, and reactive oxygen species on the orthogonal inactivation of the human immunodeficiency virus (HIV-1)

    International Nuclear Information System (INIS)

    Belanger, Julie M.; Raviv, Yossef; Viard, Mathias; Cruz, M. Jason de la; Nagashima, Kunio; Blumenthal, Robert

    2011-01-01

    Previously we reported that hydrophobic aryl azides partition into hydrophobic regions of the viral membrane of enveloped viruses and inactivate the virus upon UVA irradiation for 2 min. Prolonged irradiation (15 min) resulted in viral protein aggregation as visualized via Western blot analysis, due to reactive oxygen species (ROS) formation, with preservation of the surface antigenic epitopes. Herein, we demonstrate that these aggregates show detergent resistance and that this property may be useful towards the creation of a novel orthogonal virus inactivation strategy for use in preparing experimental vaccines. When ROS-modified HIV virus preparations were treated with 1% Triton X-100, there was an increase in the percent of viral proteins (gp41, p24) in the viral pellet after ultracentrifugation through sucrose. Transmission electron microscopy (TEM) of these detergent-resistant pellets shows some recognizable virus fragments, and immunoprecipitation studies of the gp41 aggregates suggest the aggregation is covalent in nature, involving short-range interactions.

  2. Effects of UVA Irradiation, Aryl Azides, and Reactive Oxygen Species on the Orthogonal Inactivation of the Human Immunodeficiency Virus (HIV-1)

    Science.gov (United States)

    Belanger, Julie M.; Raviv, Yossef; Viard, Mathias; de la Cruz, M. Jason; Nagashima, Kunio; Blumenthal, Robert

    2011-01-01

    Previously we reported that hydrophobic aryl azides partition into hydrophobic regions of the viral membrane of enveloped viruses and inactivate the virus upon UVA irradiation for 2 minutes. Prolonged irradiation (15 minutes) resulted in viral protein aggregation as visualized via Western blot analysis, due to reactive oxygen species (ROS) formation, with preservation of the surface antigenic epitopes. Herein, we demonstrate that these aggregates show detergent resistance and that this property may be useful towards the creation of a novel orthogonal virus inactivation strategy for use in preparing experimental vaccines. When ROS-modified HIV virus preparations were treated with 1% Triton X-100, there was an increase in the percent of viral proteins (gp41, p24) in the viral pellet after ultracentrifugation through sucrose. Transmission electron microscopy (TEM) of these detergent-resistant pellets show some recognizable virus fragments, and immunoprecipitation studies of the gp41 aggregates suggest the aggregation is covalent in nature, involving short-range interactions. PMID:21726886

  3. Protection induced by virus-like particle vaccine containing tandem repeat gene of respiratory syncytial virus G protein.

    Directory of Open Access Journals (Sweden)

    Ah-Ra Kim

    Full Text Available Respiratory syncytial virus (RSV is the leading cause of lower respiratory tract illness in infants, young children and the elderly. However, there is no licensed vaccine available against RSV infection. In this study, we generated virus-like particle (VLP vaccine and investigated the vaccine efficacy in a mouse model. For VLP vaccines, tandem gene (1-780 bp for V1 VLPs and tandem repeat gene (repeated 450-780 bp for V5 VLPs were constructed in pFastBacTM vectors, respectively. Influenza matrix protein 1 (M1 was used as a core protein in the VLPs. Notably, upon challenge infection, significantly lower virus loads were measured in the lung of mice immunized with V1 or V5 VLPs compared to those of naïve mice and formalin-inactivated RSV immunized control mice. In particular, V5 VLPs immunization showed significantly lower virus titers than V1 VLPs immunization. Furthermore, V5 VLPs immunization elicited increased memory B cells responses in the spleen. These results indicated that V5 VLP vaccine containing tandem repeat gene protein provided better protection than V1 VLPs with significantly decreased inflammation in the lungs. Thus, V5 VLPs could be a potential vaccine candidate against RSV.

  4. Rapid Bedside Inactivation of Ebola Virus for Safe Nucleic Acid Tests

    DEFF Research Database (Denmark)

    Rosenstierne, Maiken Worsøe; Karlberg, Helen; Bragstad, Karoline

    2016-01-01

    Rapid bedside inactivation of Ebola virus would be a solution for the safety of medical and technical staff, risk containment, sample transport, and high-throughput or rapid diagnostic testing during an outbreak. We show that the commercially available Magna Pure lysis/binding buffer used...... for nucleic acid extraction inactivates Ebola virus. A rapid bedside inactivation method for nucleic acid tests is obtained by simply adding Magna Pure lysis/binding buffer directly into vacuum blood collection EDTA tubes using a thin needle and syringe prior to sampling. The ready-to-use inactivation vacuum...... tubes are stable for more than 4 months, and Ebola virus RNA is preserved in the Magna Pure lysis/binding buffer for at least 5 weeks independent of the storage temperature. We also show that Ebola virus RNA can be manually extracted from Magna Pure lysis/binding buffer-inactivated samples using...

  5. 9 CFR 113.208 - Avian Encephalomyelitis Vaccine, Killed Virus.

    Science.gov (United States)

    2010-01-01

    ..., Killed Virus. 113.208 Section 113.208 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.208 Avian Encephalomyelitis Vaccine, Killed Virus. Avian...

  6. 9 CFR 113.211 - Feline Rhinotracheitis Vaccine, Killed Virus.

    Science.gov (United States)

    2010-01-01

    ... Virus. 113.211 Section 113.211 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.211 Feline Rhinotracheitis Vaccine, Killed Virus. Feline...

  7. 9 CFR 113.216 - Bovine Rhinotracheitis Vaccine, Killed Virus.

    Science.gov (United States)

    2010-01-01

    ... Virus. 113.216 Section 113.216 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.216 Bovine Rhinotracheitis Vaccine, Killed Virus. Infectious Bovine...

  8. 9 CFR 113.210 - Feline Calicivirus Vaccine, Killed Virus.

    Science.gov (United States)

    2010-01-01

    ... Virus. 113.210 Section 113.210 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.210 Feline Calicivirus Vaccine, Killed Virus. Feline Calicivirus...

  9. Inactivation of H1N1 viruses exposed to acidic ozone water

    Science.gov (United States)

    Uhm, Han S.; Lee, Kwang H.; Seong, Baik L.

    2009-10-01

    The inactivation of H1N1 viruses upon exposure to acidic ozone water was investigated using chicken allantoic fluids of different dilutions, pH values, and initial ozone concentrations. The inactivation effect of the acidic ozone water was found to be stronger than the inactivation effect of the ozone water combined with the degree of acidity, indicating a synergic effect of acidity on ozone decay in water. It is also shown that acidic ozone water with a pH value of 4 or less is very effective means of virus inactivation if provided in conjunction with an ozone concentration of 20 mg/l or higher.

  10. Correlates of protection for inactivated enterovirus 71 vaccine: the analysis of immunological surrogate endpoints.

    Science.gov (United States)

    Zhu, Wenbo; Jin, Pengfei; Li, Jing-Xin; Zhu, Feng-Cai; Liu, Pei

    2017-09-01

    Inactivated Enterovirus 71 (EV71) vaccines showed significant efficacy against the diseases associated with EV71 and a neutralizing antibody (NTAb) titer of 1:16-1:32 was suggested as the correlates of the vaccine protection. This paper aims to further estimate the immunological surrogate endpoints for the protection of inactivated EV71 vaccines and the effect factors. Pre-vaccination NTAb against EV71 at baseline (day 0), post-vaccination NTAb against EV71 at day 56, and the occurrence of laboratory-confirmed EV71-associated diseases during a 24-months follow-up period were collected from a phase 3 efficacy trial of an inactivated EV71 vaccine. We used the mixed-scaled logit model and the absolute sigmoid function by some extensions in continuous models to estimate the immunological surrogate endpoint for the EV71 vaccine protection, respectively. For children with a negative baseline of EV71 NTAb titers, an antibody level of 26.6 U/ml (1:30) was estimated to provide at least a 50% protection for 12 months, and an antibody level of 36.2 U/ml (1:42) may be needed to achieve a 50% protective level of the population for 24 months. Both the pre-vaccination NTAb level and the vaccine protective period could affect the estimation of the immunological surrogate for EV71 vaccine. A post-vaccination NTAb titer of 1:42 or more may be needed for long-term protection. NCT01508247.

  11. Ebolavirus Vaccines: Progress in the Fight Against Ebola Virus Disease.

    Science.gov (United States)

    Wu, Xiao-Xin; Yao, Hang-Ping; Wu, Nan-Ping; Gao, Hai-Nv; Wu, Hai-Bo; Jin, Chang-Zhong; Lu, Xiang-Yun; Xie, Tian-Shen; Li, Lan-Juan

    2015-01-01

    Ebolaviruses are highly infectious pathogens that cause lethal Ebola virus disease (EVD) in humans and non-human primates (NHPs). Due to their high pathogenicity and transmissibility, as well as the potential to be misused as a bioterrorism agent, ebolaviruses would threaten the health of global populations if not controlled. In this review, we describe the origin and structure of ebolaviruses and the development of vaccines from the beginning of the 1980s, including conventional ebolavirus vaccines, DNA vaccines, Ebola virus-like particles (VLPs), vaccinia virus-based vaccines, Venezuelan equine encephalitis virus (VEEV)-like replicon particles, Kunjin virus-based vaccine, recombinant Zaire Ebolavirusx2206;VP30, recombinant cytomegalovirus (CMV)-based vaccines, recombinant rabies virus (RABV)-based vaccines, recombinant paramyxovirus-based vaccines, adenovirus-based vaccines and vesicular stomatitis virus (VSV)-based vaccines. No licensed vaccine or specific treatment is currently available to counteract ebolavirus infection, although DNA plasmids and several viral vector approaches have been evaluated as promising vaccine platforms. These vaccine candidates have been confirmed to be successful in protecting NHPs against lethal infection. Moreover, these vaccine candidates were successfully advanced to clinical trials. The present review provides an update of the current research on Ebola vaccines, with the aim of providing an overview on current prospects in the fight against EVD. © 2015 The Author(s) Published by S. Karger AG, Basel.

  12. Enhanced lung disease and Th2 response following human metapneumovirus infection in mice immunized with the inactivated virus.

    Science.gov (United States)

    Hamelin, Marie-Eve; Couture, Christian; Sackett, Melanie K; Boivin, Guy

    2007-12-01

    Human metapneumovirus (hMPV) is a paramyxovirus that causes acute respiratory-tract infections in humans. The histopathological and immunological responses to hMPV infection in BALB/c mice immunized with inactivated hMPV were characterized. Animals were immunized intraperitoneally with PBS, supernatant from non-infected LLC-MK2 cells and from heat-inactivated influenza A- or hMPV-infected cells, all in incomplete Freund's adjuvant, or with heat-inactivated hMPV without adjuvant, and then infected intranasally with 10(8) TCID50 virus. Following infection, lung samples and bronchoalveolar lavages were collected for determination of viral titre and cytokine levels and for histopathological studies. On day 1, 26 % of mice immunized with inactivated hMPV and adjuvant died, compared with none in the other groups. There was more significant lung inflammation associated with eosinophilic infiltration, as well as increased levels of interleukin-4 (IL-4) and IL-5, in the bronchoalveolar lavages of mice immunized with hMPV alone or with the adjuvant. Mice from the last two groups had a 4-5 log10 decrease in their pulmonary viral titres compared with controls. Our data demonstrate the risks associated with immunization using inactivated hMPV in this animal model and that this aberrant response should be considered in the development of hMPV vaccines.

  13. 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.

  14. Long-term immunity in young adults after a single dose of inactivated Hepatitis A vaccines.

    Science.gov (United States)

    Orr, Nadav; Klement, Eyal; Gillis, David; Sela, Tamar; Kayouf, Raid; Derazne, Estela; Grotto, Itamar; Balicer, Ran; Huerta, Michael; Aviram, Lisa; Ambar, Ruhama; Epstein, Yoram; Heled, Yuval; Cohen, Dani

    2006-05-15

    We evaluated in a prospective study the immune response of naïve subjects to a single dose of inactivated Hepatitis A vaccine. Ninety-seven percent of the vaccinees sero-converted 1 month after vaccination and 93% were still positive 2 years later. All of the vaccinees had a strong booster response 2 years after the single dose. Avaxim was more immunogenic than Vaqta for the primary dose (p = 0.01 for sero-positivity, p<0.001 for antibody level) but no differences were found after boosting with Avaxim. Performance of intense physical activity during the first month after a single vaccine dose was associated with lower antibody levels (p = 0.004). This study indicates that a single dose of inactivated HAV vaccine elicits protective immune memory for at least 2 years.

  15. 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.

  16. Does a monovalent inactivated human rotavirus vaccine induce heterotypic immunity?: Evidence from animal studies

    OpenAIRE

    Jiang, Baoming; Wang, Yuhuan; Glass, Roger I.

    2013-01-01

    There is substantial evidence for broad cross-reactive immunity and heterotypic protection among human rotavirus strains in children with natural infection or with monovalent Rotarix vaccination. In this commentary, we addressed this same topic by testing sera of guinea pigs and gnotobiotic piglets that were intramuscularly immunized with an inactivated human rotavirus vaccine and also demonstrated a broad cross-protective immunity among human rotavirus strains. Our findings from a single hum...

  17. Systemic and local immune response in pigs intradermally and intramuscularly injected with inactivated Mycoplasma hyopneumoniae vaccines.

    Science.gov (United States)

    Martelli, P; Saleri, R; Cavalli, V; De Angelis, E; Ferrari, L; Benetti, M; Ferrarini, G; Merialdi, G; Borghetti, P

    2014-01-31

    The systemic and respiratory local immune response induced by the intradermal administration of a commercial inactivated Mycoplasma hyopneumoniae whole-cell vaccine (Porcilis(®) MHYO ID ONCE - MSD AH) in comparison with two commercial vaccines administered via the intramuscular route and a negative control (adjuvant only) was investigated. Forty conventional M. hyopneumoniae-free pigs were randomly assigned to four groups (ten animals each): Group A=intradermal administration of the test vaccine by using the needle-less IDAL(®) vaccinator at a dose of 0.2 ml; Group B=intramuscular administration of a commercially available vaccine (vaccine B); Group C=intramuscular administration of the adjuvant only (2 ml of X-solve adjuvant); Group D=intramuscular administration of a commercially available vaccine (vaccine D). Pigs were vaccinated at 28 days of age. Blood and bronchoalveolar lavage (BAL) fluid samples were collected at vaccination (blood only), 4 and 8 weeks post-vaccination. Serum and BAL fluid were tested for the presence of antibodies by ELISA test. Peripheral blood monomorphonuclear cells (PBMC) were isolated to quantify the number of IFN-γ secreting cells by ELISpot. Moreover, cytokine gene expression from the BAL fluid was performed. Total antibodies against M. hyopneumoniae and specific IgG were detected in serum of intradermally and intramuscularly (vaccine B only) vaccinated pigs at 4 and 8 weeks post-vaccination. M. hyopneumoniae specific IgA were detected in BAL fluid from vaccinated animals (Groups A and B) but not from controls and animals vaccinated with the bacterin D (padministration of an adjuvanted bacterin induces both systemic and mucosal immune responses. Moreover, the intramuscularly administered commercial vaccines each had a different ability to stimulate the immune response both systemically and locally. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. Immunization with SARS coronavirus vaccines leads to pulmonary immunopathology on challenge with the SARS virus.

    Directory of Open Access Journals (Sweden)

    Chien-Te Tseng

    Full Text Available Severe acute respiratory syndrome (SARS emerged in China in 2002 and spread to other countries before brought under control. Because of a concern for reemergence or a deliberate release of the SARS coronavirus, vaccine development was initiated. Evaluations of an inactivated whole virus vaccine in ferrets and nonhuman primates and a virus-like-particle vaccine in mice induced protection against infection but challenged animals exhibited an immunopathologic-type lung disease.Four candidate vaccines for humans with or without alum adjuvant were evaluated in a mouse model of SARS, a VLP vaccine, the vaccine given to ferrets and NHP, another whole virus vaccine and an rDNA-produced S protein. Balb/c or C57BL/6 mice were vaccinated i.m. on day 0 and 28 and sacrificed for serum antibody measurements or challenged with live virus on day 56. On day 58, challenged mice were sacrificed and lungs obtained for virus and histopathology.All vaccines induced serum neutralizing antibody with increasing dosages and/or alum significantly increasing responses. Significant reductions of SARS-CoV two days after challenge was seen for all vaccines and prior live SARS-CoV. All mice exhibited histopathologic changes in lungs two days after challenge including all animals vaccinated (Balb/C and C57BL/6 or given live virus, influenza vaccine, or PBS suggesting infection occurred in all. Histopathology seen in animals given one of the SARS-CoV vaccines was uniformly a Th2-type immunopathology with prominent eosinophil infiltration, confirmed with special eosinophil stains. The pathologic changes seen in all control groups lacked the eosinophil prominence.These SARS-CoV vaccines all induced antibody and protection against infection with SARS-CoV. However, challenge of mice given any of the vaccines led to occurrence of Th2-type immunopathology suggesting hypersensitivity to SARS-CoV components was induced. Caution in proceeding to application of a SARS-CoV vaccine in

  19. Live-Attenuated Respiratory Syncytial Virus Vaccines

    Science.gov (United States)

    Buchholz, Ursula J.; Collins, Peter L.

    2016-01-01

    Live-attenuated respiratory syncytial virus (RSV) vaccines offer several advantages for immunization of infants and young children: (1) they do not cause vaccine-associated enhanced RSV disease; (2) they broadly stimulate innate, humoral, and cellular immunity, both systemically and locally in the respiratory tract; (3) they are delivered intranasally; and (4) they replicate in the upper respiratory tract of young infants despite the presence of passively acquired maternally derived RSV neutralizing antibody. This chapter describes early efforts to develop vaccines through the classic methods of serial cold-passage and chemical mutagenesis, and recent efforts using reverse genetics to derive attenuated derivatives of wild-type (WT) RSV and to develop parainfluenza vaccine vectors that express RSV surface glycoproteins. PMID:24362694

  20. Unravelling the genetic components involved in the immune response of pigs vaccinated against influenza virus.

    Science.gov (United States)

    Zanella, Ricardo; Gava, Danielle; Peixoto, Jane de Oliveira; Schaefer, Rejane; Ciacci-Zanella, Janice Reis; Biondo, Natalha; da Silva, Marcos Vinicius Gualberto Barbosa; Cantão, Maurício Egídio; Ledur, Mônica Corrêa

    2015-12-02

    A genome-wide association study for immune response to influenza vaccination in a crossbred swine population was conducted. Swine influenza is caused by influenza A virus (FLUAV) which is considered one of the most prevalent respiratory pathogens in swine worldwide. The main strategy used to control influenza in swine herds is through vaccination. However, the currently circulating FLUAV subtypes in swine are genetically and antigenically diverse and their interaction with the host genetics poses a challenge for the production of efficacious and cross-protective vaccines. In this study, 103 pigs vaccinated with an inactivated H1N1 pandemic virus were genotyped with the Illumina PorcineSNP60V2 BeadChip for the identification of genetic markers associated with immune response efficacy to influenza A virus vaccination. Immune response was measured based on the presence or absence of HA (hemagglutinin) and NP (nucleoprotein) antibodies induced by vaccination and detected in swine sera by the hemagglutination inhibition (HI) and ELISA assays, respectively. The ELISA test was also used as a measurement of antibody levels produced following the FLUAV vaccination. Associations were tested with x(2) test for a case and control data and using maximum likelihood method for the quantitative data, where a moderate association was considered if pimmune response. Using the response to vaccination measured by ELISA as a qualitative and quantitative phenotype, four genomic regions were associated with immune response: one on SSC12 and three on chromosomes SSC1, SSC7, and SSC15, respectively. Those regions harbor important functional candidate genes possibly involved with the degree of immune response to vaccination. These results show an important role of host genetics in the immune response to influenza vaccination. Genetic selection for pigs with better response to FLUAV vaccination might be an alternative to reduce the impact of influenza virus infection in the swine industry

  1. Effects of formalin-inactivated respiratory syncytial virus (FI-RSV in the perinatal lamb model of RSV.

    Directory of Open Access Journals (Sweden)

    Rachel J Derscheid

    Full Text Available Respiratory syncytial virus (RSV is the most frequent cause of bronchiolitis in infants and children worldwide. There are currently no licensed vaccines or effective antivirals. The lack of a vaccine is partly due to increased caution following the aftermath of a failed clinical trial of a formalin-inactivated RSV vaccine (FI-RSV conducted in the 1960's that led to enhanced disease, necessitating hospitalization of 80% of vaccine recipients and resulting in two fatalities. Perinatal lamb lungs are similar in size, structure and physiology to those of human infants and are susceptible to human strains of RSV that induce similar lesions as those observed in infected human infants. We sought to determine if perinatal lambs immunized with FI-RSV would develop key features of vaccine-enhanced disease. This was tested in colostrum-deprived lambs immunized at 3-5 days of age with FI-RSV followed two weeks later by RSV infection. The FI-RSV-vaccinated lambs exhibited several key features of RSV vaccine-enhanced disease, including reduced RSV titers in bronchoalveolar lavage fluid and lung, and increased infiltration of peribronchiolar and perivascular lymphocytes compared to lambs either undergoing an acute RSV infection or naïve controls; all features of RSV vaccine-enhanced disease. These results represent a first step proof-of-principle demonstration that the lamb can develop altered responses to RSV following FI-RSV vaccination. The lamb model may be useful for future mechanistic studies as well as the assessment of RSV vaccines designed for infants.

  2. 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...

  3. Evaluation of seasonal influenza vaccines for H1N1pdm09 and type B viruses based on a replication-incompetent PB2-KO virus.

    Science.gov (United States)

    Ui, Hiroki; Yamayoshi, Seiya; Uraki, Ryuta; Kiso, Maki; Oishi, Kohei; Murakami, Shin; Mimori, Shigetaka; Kawaoka, Yoshihiro

    2017-04-04

    Vaccination is the first line of protection against influenza virus infection in humans. Although inactivated and live-attenuated vaccines are available, each vaccine has drawbacks in terms of immunogenicity and safety. To overcome these issues, our group has developed a replication-incompetent PB2-knockout (PB2-KO) influenza virus that replicates only in PB2-expressing cells. Here we generated PB2-KO viruses possessing the hemagglutinin (HA) and neuraminidase (NA) segments from H1N1pdm09 or type B viruses and tested their vaccine potential. The two PB2-KO viruses propagated efficiently in PB2-expressing cells, and expressed chimeric HA as expected. Virus-specific IgG and IgA antibodies were detected in mice immunized with the viruses, and the immunized mice showed milder clinical signs and/or lower virus replication levels in the respiratory tract upon virus challenge. Our results indicate that these PB2-KO viruses have potential as vaccine candidates. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Decrease in formalin-inactivated respiratory syncytial virus (FI-RSV enhanced disease with RSV G glycoprotein peptide immunization in BALB/c mice.

    Directory of Open Access Journals (Sweden)

    Gertrud U Rey

    Full Text Available Respiratory syncytial virus (RSV is a high priority target for vaccine development. One concern in RSV vaccine development is that a non-live virus vaccine would predispose for enhanced disease similar to that seen with the formalin inactivated RSV (FI-RSV vaccine. Since a mAb specific to RSV G protein can reduce pulmonary inflammation and eosinophilia seen after RSV infection of FI-RSV vaccinated mice, we hypothesized that RSV G peptides that induce antibodies with similar reactivity may limit enhanced disease after subunit or other non-live RSV vaccines. In support of this hypothesis, we show that FI-RSV vaccinated mice administered RSV G peptide vaccines had a significant reduction in enhanced disease after RSV challenge. These data support the importance of RSV G during infection to RSV disease pathogenesis and suggest that use of appropriately designed G peptide vaccines to reduce the risk of enhanced disease with non-live RSV vaccines merits further study.

  5. Experimental induction of chicken amyloid A amyloidosis in white layer chickens by inoculation with inactivated vaccines.

    Science.gov (United States)

    Habibi, Wazir Ahmad; Hirai, Takuya; Niazmand, Mohammad Hakim; Okumura, Naoko; Yamaguchi, Ryoji

    2017-10-01

    We investigated the amyloidogenic potential of inactivated vaccines and the localized production of serum amyloid A (SAA) at the injection site in white layer chickens. Hens in the treated group were injected intramuscularly three times with high doses of inactivated oil-emulsion Salmonella Enteritidis vaccine and multivalent viral and bacterial inactivated oil-emulsion vaccines at two-week intervals. Chickens in the control group did not receive any inoculum. In the treated group, emaciation and granulomas were present, while several chickens died between 4 and 6 weeks after the first injection. Hepatomegaly was seen at necropsy, and the liver parenchyma showed inconsistent discolouration with patchy green to yellowish-brown areas, or sometimes red-brown areas with haemorrhage. Amyloid deposition in the liver, spleen, duodenum, and at injection sites was demonstrated using haematoxylin and eosin staining, Congo red, and immunohistochemistry. The incidence of chicken amyloid A (AA) amyloidosis was 47% (28 of 60) in the treated group. In addition, RT-PCR was used to identify chicken SAA mRNA expression in the liver and at the injection sites. Furthermore, SAA mRNA was detected by in situ hybridization in fibroblasts at the injection sites, and also in hepatocytes. We believe that this is the first report of the experimental induction of systemic AA amyloidosis in white layer chickens following repeated inoculation with inactivated vaccines without the administration of amyloid fibrils or other amyloid-enhancing factors.

  6. Regulatory Acceptance and Use of Serology for Inactivated Veterinary Rabies Vaccines

    NARCIS (Netherlands)

    Schiffelers, Marie-Jeanne W. A.; Blaauboer, Bas J.; Bakker, Wieger E.; Hendriksen, Coenraad F. M.

    2015-01-01

    In April 2013 the mouse antibody serum neutralization test (SNT) was formally incorporated into European Pharmacopoeia monograph 0451 for potency testing of inactivated veterinary rabies vaccines. The SNT is designed to replace the highly variable and pain and distress causing NIH mouse rabies

  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. Immunogenicity, safety, and antibody persistence at 3, 5, and 10 years postvaccination in adolescents randomized to booster immunization with a combined tetanus, diphtheria, 5-component acellular pertussis, and inactivated poliomyelitis vaccine administered with a hepatitis B virus vaccine concurrently or 1 month apart.

    Science.gov (United States)

    Embree, Joanne; Law, Barbara; Voloshen, Tim; Tomovici, Antigona

    2015-03-01

    An understanding of the antibody persistence elicited by a combined tetanus, diphtheria, 5-component acellular pertussis, and inactivated poliovirus vaccine (Tdap-IPV) after adolescent vaccination is important to optimize booster dosing intervals. Our objectives were to compare the safety and immunogenicity of Tdap-IPV coadministered with hepatitis B vaccine (HepB) and sequential administration and evaluate humoral immunity at 3, 5, and 10 years after Tdap-IPV vaccination in adolescents. This phase II randomized, controlled, and open-label study enrolled 280 11- to 14-year-old adolescents with up to 10 years postvaccination follow-up. Group 1 (n = 145) received Tdap-IPV, followed by a HepB dose 1 month later, and group 2 (n = 135) received both vaccines simultaneously. No consistent increases in solicited reactions or unsolicited adverse events occurred with coadministration. All vaccinees attained seroprotective antibody levels at ≥0.01 IU/ml for diphtheria and tetanus, at a ≥1:8 dilution for poliovirus (serotypes 1, 2, and 3), and ≥10 mIU/ml for hepatitis B at 1 month postvaccination. Clinically relevant immunologic interactions did not occur with coadministration. For pertussis, all participants achieved seropositivity levels (at or above the lower limit of quantitation), and 72.7% to 95.8% had 4-fold increases in pertussis antibodies at 1 month postvaccination. At 10 years postvaccination, the remaining participants (62.8% of the original cohort) maintained seroprotective levels of ≥0.01 IU/ml for diphtheria and tetanus, a ≥1:8 dilution for all 3 poliovirus serotypes, and 74.1% to 98.2% maintained pertussis seropositivity levels depending on the antigen tested. There were no differences between the groups. These results support the coadministration of Tdap-IPV and HepB to adolescents and suggest that vaccination with Tdap-IPV can offer protection for 10 years after an adolescent booster vaccination. Copyright © 2015, American Society for Microbiology

  9. 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

  10. Sunlight inactivation of human viruses and bacteriophages in coastal waters containing natural photosensitizers.

    Science.gov (United States)

    Silverman, Andrea I; Peterson, Britt M; Boehm, Alexandria B; McNeill, Kristopher; Nelson, Kara L

    2013-02-19

    Sunlight inactivation of poliovirus type 3 (PV3), adenovirus type 2 (HAdV2), and two bacteriophage (MS2 and PRD1) was investigated in an array of coastal waters to better understand solar inactivation mechanisms and the effect of natural water constituents on observed inactivation rates (k(obs)). Reactor scale inactivation experiments were conducted using a solar simulator, and k(obs) for each virus was measured in a sensitizer-free control and five unfiltered surface water samples collected from different sources. k(obs) values varied between viruses in the same water matrix, and for each virus in different matrices, with PV3 having the fastest and MS2 the slowest k(obs) in all waters. When exposed to full-spectrum sunlight, the presence of photosensitizers increased k(obs) of HAdV2, PRD1 and MS2, but not PV3, which provides evidence that the exogenous sunlight inactivation mechanism, involving damage by exogenously produced reactive intermediates, played a greater role for these viruses. While PV3 inactivation was observed to be dominated by endogenous mechanisms, this may be due to a masking of exogenous k(obs) by significantly faster endogenous k(obs). Results illustrate that differences in water composition can shift absolute and relative inactivation rates of viruses, which has important implications for natural wastewater treatment systems, solar disinfection (SODIS), and the use of indicator organisms for monitoring water quality.

  11. Immune response to a heat-inactivated hepatitis B vaccine in patients undergoing hemodialysis. Enhancement of the response by increasing the dose of hepatitis B surface antigen from 3 to 27 micrograms

    NARCIS (Netherlands)

    Lelie, P. N.; Reesink, H. W.; de Jong-van Manen, S. T.; Dees, P. J.; Reerink-Brongers, E. E.

    1985-01-01

    In a randomized trial, 227 patients undergoing hemodialysis who were seronegative for all markers of hepatitis B virus were immunized at monthly intervals with three doses of either 3 micrograms or 27 micrograms of heat-inactivated hepatitis B HB-vaccine (CLB). Five months after the first injection,

  12. Studies of inactivation mechanism of non-enveloped icosahedral virus by a visible ultrashort pulsed laser.

    Science.gov (United States)

    Tsen, Shaw-Wei D; Kingsley, David H; Poweleit, Christian; Achilefu, Samuel; Soroka, Douglas S; Wu, T C; Tsen, Kong-Thon

    2014-02-05

    Low-power ultrashort pulsed (USP) lasers operating at wavelengths of 425 nm and near infrared region have been shown to effectively inactivate viruses such as human immunodeficiency virus (HIV), M13 bacteriophage, and murine cytomegalovirus (MCMV). It was shown previously that non-enveloped, helical viruses such as M13 bacteriophage, were inactivated by a USP laser through an impulsive stimulated Raman scattering (ISRS) process. Recently, enveloped virus like MCMV has been shown to be inactivated by a USP laser via protein aggregation induced by an ISRS process. However, the inactivation mechanism for a clinically important class of viruses--non-enveloped, icosahedral viruses remains unknown. We have ruled out the following four possible inactivation mechanisms for non-enveloped, icosahedral viruses, namely, (1) inactivation due to ultraviolet C (UVC) photons produced by non-linear optical process of the intense, fundamental laser beam at 425 nm; (2) inactivation caused by thermal heating generated by the direct laser absorption/heating of the virion; (3) inactivation resulting from a one-photon absorption process via chromophores such as porphyrin molecules, or indicator dyes, potentially producing reactive oxygen or other species; (4) inactivation by the USP lasers in which the extremely intense laser pulse produces shock wave-like vibrations upon impact with the viral particle. We present data which support that the inactivation mechanism for non-enveloped, icosahedral viruses is the impulsive stimulated Raman scattering process. Real-time PCR experiments show that, within the amplicon size of 273 bp tested, there is no damage on the genome of MNV-1 caused by the USP laser irradiation. We conclude that our model non-enveloped virus, MNV-1, is inactivated by the ISRS process. These studies provide fundamental knowledge on photon-virus interactions on femtosecond time scales. From the analysis of the transmission electron microscope (TEM) images of viral particles

  13. Five-year antibody persistence in children after one dose of inactivated or live attenuated hepatitis A vaccine.

    Science.gov (United States)

    Zhang, Zhilun; Zhu, Xiangjun; Hu, Yuansheng; Liang, Miao; Sun, Jin; Song, Yufei; Yang, Qi; Ji, Haiquan; Zeng, Gang; Song, Lifei; Chen, Jiangting

    2017-06-03

    In China, both inactivated hepatitis A (HA) vaccine and live attenuated HA vaccine are available. We conducted a trial to evaluate 5-year immune persistence induced by one dose of inactivated or live attenuated HA vaccines in children. Subjects with no HA vaccination history had randomly received one dose of inactivated or live attenuated HA vaccine at 18-60 months of age. Anti-HAV antibody concentrations were measured before vaccination and at the first, second, and fifth year after vaccination. Suspected cases of hepatitis A were monitored during the study period. A total of 332 subjects were enrolled and 182 provided evaluable serum samples at all planned time points. seropositive rate at 5 y was 85.9% in the inactivated HA vaccine group and 90.7% in the live attenuated HA vaccine group. GMCs were 76.3% mIU/ml (95% CI: 61.7 - 94.4) and 66.8mIU/ml (95% CI: 57.8 - 77.3), respectively. No significant difference in antibody persistence between 2 groups was found. No clinical hepatitis A case was reported. A single dose of an inactivated or live attenuated HA vaccine at 18-60 months of age resulted in high HAV seropositive rate and anti-HAV antibody concentrations that lasted for at least 5 y.

  14. Inactivated polio vaccination using a microneedle patch is immunogenic in the rhesus macaque.

    Science.gov (United States)

    Edens, Chris; Dybdahl-Sissoko, Naomi C; Weldon, William C; Oberste, M Steven; Prausnitz, Mark R

    2015-09-08

    The phased replacement of oral polio vaccine (OPV) with inactivated polio vaccine (IPV) is expected to significantly complicate mass vaccination campaigns, which are an important component of the global polio eradication endgame strategy. To simplify mass vaccination with IPV, we developed microneedle patches that are easy to administer, have a small package size, generate no sharps waste and are inexpensive to manufacture. When administered to rhesus macaques, neutralizing antibody titers were equivalent among monkeys vaccinated using microneedle patches and conventional intramuscular injection for IPV types 1 and 2. Serologic response to IPV type 3 vaccination was weaker after microneedle patch vaccination compared to intramuscular injection; however, we suspect the administered type 3 dose was lower due to a flawed pre-production IPV type 3 analytical method. IPV vaccination using microneedle patches was well tolerated by the monkeys. We conclude that IPV vaccination using a microneedle patch is immunogenic in rhesus macaques and may offer a simpler method of IPV vaccination of people to facilitate polio eradication. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. The immunogenicity of tetravalent dengue DNA vaccine in mice pre-exposed to Japanese encephalitis or Dengue virus antigens.

    Science.gov (United States)

    Prompetchara, Eakachai; Ketloy, Chutitorn; Keelapang, Poonsook; Sittisombut, Nopporn; Ruxrungtham, Kiat

    2015-09-01

    Asian countries are an endemic area for both dengue (DENV) and Japanese encephalitis viruses (JEV). While JEV vaccines have been used extensively in this region, DENV vaccines remains under development. Whether preexisting naturally acquired or vaccination-induced immunity against JEV may affect the immune response to dengue vaccine candidate is unclear. In this study we used mice previously immunized with JEV vaccines to evaluate the impact on dengue-specific neutralizing antibody responses to a tetravalent dengue DNA vaccine candidate (TDNA). A tetravalent cocktail of plasmids encoding pre-membrane and envelope proteins from each dengue serotype was administered into mice which had been previously primed with inactivated or live-attenuated JEV vaccines, or dengue serotype2 virus (DENV-2). Neutralizing antibody response was measured employing a plaque reduction neutralization test at two weeks after the priming and at four weeks after the second dose of the dengue tetravalent plasmids. Inactivated or live-attenuated JEV vaccines, or DENV-2 induced low levels of neutralizing antibodies against the homologous viruses (JE and dengue virus, respectively). DENV-2 injection induced also low levels of cross-reactive antibodies against DENV-1, -3 and -4. JEV vaccines have no effect on the dengue-specific neutralizing antibody responses to the subsequent TDNA immunization. Pre-exposure to DENV-2 infection increased DENV-2 specific response neutralizing antibody to two doses of TDNA plasmids by six folds, but did not affect antibody response to other serotypes. Priming with JEV vaccines did not impact on dengue virus-specific neutralizing antibody response to a dengue TDNA vaccine candidate in mice.

  16. A universal influenza virus vaccine candidate confers protection against pandemic H1N1 infection in preclinical ferret studies.

    Science.gov (United States)

    Nachbagauer, Raffael; Liu, Wen-Chun; Choi, Angela; Wohlbold, Teddy John; Atlas, Talia; Rajendran, Madhusudan; Solórzano, Alicia; Berlanda-Scorza, Francesco; García-Sastre, Adolfo; Palese, Peter; Albrecht, Randy A; Krammer, Florian

    2017-01-01

    Influenza viruses evade human adaptive immune responses due to continuing antigenic changes. This makes it necessary to re-formulate and re-administer current seasonal influenza vaccines on an annual basis. Our pan-influenza vaccination approach attempts to redirect antibody responses from the variable, immuno-dominant hemagglutinin head towards the conserved-but immuno-subdominant-hemagglutinin stalk. The strategy utilizes sequential immunization with chimeric hemagglutinin-based vaccines expressing exotic head domains, and a conserved hemagglutinin stalk. We compared a live-attenuated influenza virus prime followed by an inactivated split-virus boost to two doses of split-virus vaccines and assessed the impact of adjuvant on protection against challenge with pandemic H1N1 virus in ferrets. All tested immunization regimens successfully induced broadly cross-reactive antibody responses. The combined live-attenuated/split virus vaccination conferred superior protection against pandemic H1N1 infection compared to two doses of split-virus vaccination. Our data support advancement of this chimeric hemagglutinin-based vaccine approach to clinical trials in humans.

  17. Hendra virus and Nipah virus animal vaccines.

    Science.gov (United States)

    Broder, Christopher C; Weir, Dawn L; Reid, Peter A

    2016-06-24

    Hendra virus (HeV) and Nipah virus (NiV) are zoonotic viruses that emerged in the mid to late 1990s causing disease outbreaks in livestock and people. HeV appeared in Queensland, Australia in 1994 causing a severe respiratory disease in horses along with a human case fatality. NiV emerged a few years later in Malaysia and Singapore in 1998-1999 causing a large outbreak of encephalitis with high mortality in people and also respiratory disease in pigs which served as amplifying hosts. The key pathological elements of HeV and NiV infection in several species of mammals, and also in people, are a severe systemic and often fatal neurologic and/or respiratory disease. In people, both HeV and NiV are also capable of causing relapsed encephalitis following recovery from an acute infection. The known reservoir hosts of HeV and NiV are several species of pteropid fruit bats. Spillovers of HeV into horses continue to occur in Australia and NiV has caused outbreaks in people in Bangladesh and India nearly annually since 2001, making HeV and NiV important transboundary biological threats. NiV in particular possesses several features that underscore its potential as a pandemic threat, including its ability to infect humans directly from natural reservoirs or indirectly from other susceptible animals, along with a capacity of limited human-to-human transmission. Several HeV and NiV animal challenge models have been developed which have facilitated an understanding of pathogenesis and allowed for the successful development of both active and passive immunization countermeasures. Published by Elsevier Ltd.

  18. Immunogenicity and Safety of an Inactivated Rift Valley Fever Vaccine in a 19-Year Study

    Science.gov (United States)

    2011-02-26

    quently emerged in the Mideast [4,5]. Introduction of RVF virus to areas of the world where the Aedes mosquito vector resides could have a significant...against lethal Rift Valley fever (RVFV) infection in transgenic IFNAR(−/−) mice induced by different DNA vaccination regimens. Vaccine 2010;28:2937–44

  19. DIVA vaccination strategies for avian influenza virus.

    Science.gov (United States)

    Suarez, David L

    2012-12-01

    Vaccination for both low pathogenicity avian influenza and highly pathogenic avian influenza is commonly used by countries that have become endemic for avian influenza virus, but stamping-out policies are still common for countries with recently introduced disease. Stamping-out policies of euthanatizing infected and at-risk flocks has been an effective control tool, but it comes at a high social and economic cost. Efforts to identify alternative ways to respond to outbreaks without widespread stamping out has become a goal for organizations like the World Organisation for Animal Health. A major issue with vaccination for avian influenza is trade considerations because countries that vaccinate are often considered to be endemic for the disease and they typically lose their export markets. Primarily as a tool to promote trade, the concept of DIVA (differentiate infected from vaccinated animals) has been considered for avian influenza, but the goal for trade is to differentiate vaccinated and not-infected from vaccinated and infected animals because trading partners are unwilling to accept infected birds. Several different strategies have been investigated for a DIVA strategy, but each has advantages and disadvantages. A review of current knowledge on the research and implementation of the DIVA strategy will be discussed with possible ways to implement this strategy in the field. The increased desire for a workable DIVA strategy may lead to one of these ideas moving from the experimental to the practical.

  20. Coxsackievirus A 16 infection does not interfere with the specific immune response induced by an enterovirus 71 inactivated vaccine in rhesus monkeys.

    Science.gov (United States)

    Wang, Jingjing; Qi, Sudong; Zhang, Xiaolong; Zhang, Ying; Liu, Longding; Che, Yanchun; He, Zhanlong; Zhao, Yuan; Lu, Shuaiyao; Yu, Wenhai; Li, Qihan

    2014-07-31

    Hand, foot and mouth disease is usually caused by enterovirus 71 (EV71) and coxsackievirus A 16 (CA16), which are members of the Picornaviridae family. In the present study, the characteristics of the immune response induced by an EV71 inactivated vaccine (made from human diploid cells) were explored in the presence of CA16 infection, based on the previously established neonatal rhesus monkey model. The typical clinical manifestations, including body temperature, viral viremia and virus shedding in the mouth, pharynx and feces, were characterized. A specific neutralizing antibody assay showed that the specific immune response induced by the EV71 inactivated vaccine was active against EV71 but not against CA16. No remarkable fluctuation in proinflammatory cytokine release was identified in the serum of immunized monkeys with EV71 vaccine and CA16 infections subsequently. The results showed that the specific immune response induced by the EV71 inactivated vaccine is effective against EV71 infection but is not affected by CA16 infection. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Virus-like particle vaccines containing F or F and G proteins confer protection against respiratory syncytial virus without pulmonary inflammation in cotton rats.

    Science.gov (United States)

    Hwang, Hye Suk; Kim, Ki-Hye; Lee, Youri; Lee, Young-Tae; Ko, Eun-Ju; Park, SooJin; Lee, Jong Seok; Lee, Byung-Cheol; Kwon, Young-Man; Moore, Martin L; Kang, Sang-Moo

    2017-05-04

    Vaccine-enhanced disease has been a major obstacle in developing a safe vaccine against respiratory syncytial virus (RSV). This study demonstrates the immunogenicity, efficacy, and safety of virus-like particle (VLP) vaccines containing RSV F (F VLP), G (G VLP), or F and G proteins (FG VLP) in cotton rats. RSV specific antibodies were effectively induced by vaccination of cotton rats with F VLP or FG VLP vaccines. After challenge, lung RSV clearance was observed with RSV F, G, FG VLP, and formalin inactivated RSV (FI-RSV) vaccines. Upon RSV infection, cotton rats with RSV VLP vaccines were protected against airway hyper-responsiveness and weight loss, which are different from FI-RSV vaccination exhibiting vaccine-enhanced disease of airway obstruction, weight loss, and severe histopathology with eosinophilia and mucus production. FG VLP and F VLP vaccines did not cause pulmonary inflammation whereas G VLP induced moderate lung inflammation with eosinophilia and mucus production. In particular, F VLP and FG VLP vaccines were found to be effective in inducing antibody secreting cell responses in bone marrow and lymphoid organs as well as avoiding the induction of T helper type 2 cytokines. These results provide further evidence to develop a safe RSV vaccine based on VLP platforms.

  2. Inactivated and subunit vaccines against porcine reproductive and respiratory syndrome: current status and future direction

    Science.gov (United States)

    Within a few years of its emergence in the late 1980's, the PRRS virus had spread globally to become the foremost infectious disease concern for the pork industry. Since 1994, modified live-attenuated vaccines against porcine reproductive and respiratory syndrome virus (PRRSV-MLV) have been widely u...

  3. 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.

  4. Study of the integrated immune response induced by an inactivated EV71 vaccine.

    Directory of Open Access Journals (Sweden)

    Longding Liu

    Full Text Available Enterovirus 71 (EV71, a major causative agent of hand-foot-and-mouth disease (HFMD, causes outbreaks among children in the Asia-Pacific region. A vaccine is urgently needed. Based on successful pre-clinical work, phase I and II clinical trials of an inactivated EV71 vaccine, which included the participants of 288 and 660 respectively, have been conducted. In the present study, the immune response and the correlated modulation of gene expression in the peripheral blood mononuclear cells (PBMCs of 30 infants (6 to 11 months immunized with this vaccine or placebo and consented to join this study in the phase II clinical trial were analyzed. The results showed significantly greater neutralizing antibody and specific T cell responses in vaccine group after two inoculations on days 0 and 28. Additionally, more than 600 functional genes that were up- or down-regulated in PBMCs were identified by the microarray assay, and these genes included 68 genes associated with the immune response in vaccine group. These results emphasize the gene expression profile of the immune system in response to an inactivated EV71 vaccine in humans and confirmed that such an immune response was generated as the result of the positive mobilization of the immune system. Furthermore, the immune response was not accompanied by the development of a remarkable inflammatory response.NCT01391494 and NCT01512706.

  5. Advances in the development of influenza virus vaccines.

    Science.gov (United States)

    Krammer, Florian; Palese, Peter

    2015-03-01

    Influenza virus infections are a major public health concern and cause significant morbidity and mortality worldwide. Current influenza virus vaccines are an effective countermeasure against infection but need to be reformulated almost every year owing to antigenic drift. Furthermore, these vaccines do not protect against novel pandemic strains, and the timely production of pandemic vaccines remains problematic because of the limitations of current technology. Several improvements have been made recently to enhance immune protection induced by seasonal and pandemic vaccines, and to speed up production in case of a pandemic. Importantly, vaccine constructs that induce broad or even universal influenza virus protection are currently in preclinical and clinical development.

  6. Ebola Virus and Marburg Virus in Human Milk Are Inactivated by Holder Pasteurization.

    Science.gov (United States)

    Hamilton Spence, Erin; Huff, Monica; Shattuck, Karen; Vickers, Amy; Yun, Nadezda; Paessler, Slobodan

    2017-05-01

    Potential donors of human milk are screened for Ebola virus (EBOV) using standard questions, but testing for EBOV and Marburg virus (MARV) is not part of routine serological testing performed by milk banks. Research aim: This study tested the hypothesis that EBOV would be inactivated in donor human milk (DHM) by standard pasteurization techniques (Holder) used in all North American nonprofit milk banks. Milk samples were obtained from a nonprofit milk bank. They were inoculated with EBOV (Zaire strain) and MARV (Angola strain) and processed by standard Holder pasteurization technique. Plaque assays for EBOV and MARV were performed to detect the presence of virus after pasteurization. Neither EBOV nor MARV was detectable by viral plaque assay in DHM or culture media samples, which were pasteurized by the Holder process. EBOV and MARV are safely inactivated in human milk by standard Holder pasteurization technique. Screening for EBOV or MARV beyond questionnaire and self-deferral is not needed to ensure safety of DHM for high-risk infants.

  7. 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.

  8. The Impact of Capsid Proteins on Virus Removal and Inactivation During Water Treatment Processes.

    Science.gov (United States)

    Mayer, Brooke K; Yang, Yu; Gerrity, Daniel W; Abbaszadegan, Morteza

    2015-01-01

    This study examined the effect of the amino acid composition of protein capsids on virus inactivation using ultraviolet (UV) irradiation and titanium dioxide photocatalysis, and physical removal via enhanced coagulation using ferric chloride. Although genomic damage is likely more extensive than protein damage for viruses treated using UV, proteins are still substantially degraded. All amino acids demonstrated significant correlations with UV susceptibility. The hydroxyl radicals produced during photocatalysis are considered nonspecific, but they likely cause greater overall damage to virus capsid proteins relative to the genome. Oxidizing chemicals, including hydroxyl radicals, preferentially degrade amino acids over nucleotides, and the amino acid tyrosine appears to strongly influence virus inactivation. Capsid composition did not correlate strongly to virus removal during physicochemical treatment, nor did virus size. Isoelectric point may play a role in virus removal, but additional factors are likely to contribute.

  9. 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...

  10. HUMAN PAPILLOMA VIRUS. NEW OPPORTUNITIES FOR VACCINATION

    Directory of Open Access Journals (Sweden)

    A. G. Gaivoronskaya

    2014-01-01

    Full Text Available One of the most important problems in the modern world is the papilloma virus infection. As is known, this is the most widely spread sexually-transmitted infection. The human papilloma virus is responsible for the occurrence of such a terrible disease as cervical cancer, which ranks third after breast cancer and cancer of the body in the structure of oncological morbidity organs of the reproductive system and mammary glands in women. The other manifestations of the papilloma virus infection are pointed condyloma genital warts, which occur frequently both in men and in women. The only reliable method of the prevention of the papilloma virus infection is immunization. The authors present new data regarding the use of bivalent vaccine, including a new scheme of immunization for girls from nine to fourteen years old. Foreign investigations showed that the double scheme of introduction of the vaccine in young girls is as effective as a triple scheme of introduction in the category of women over 15 years of age.

  11. 9 CFR 113.311 - Bovine Virus Diarrhea Vaccine.

    Science.gov (United States)

    2010-01-01

    ... shall be tested for virus titer using the titration method used in paragraph (c)(2) of this section. To... titrations shall be conducted on a sample of the vaccine virus dilution used. (3) At least once during a...

  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. Immune response in cattle vaccinated against rabies

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    Oliveira Alexandre Nunes de

    2000-01-01

    Full Text Available In order to determine the best type of rabies vaccine to use as a booster, 78 serological samples from singly vaccinated cattle were analyzed by counterimmunoelectrophoresis technique. The animals were divided into several groups, received the first vaccine dose with modified live virus vaccine (ERA strain and were revaccinated with inactivated virus or modified live virus vaccines. Boosters were given at 2, 4, 8, 12 and 16 weeks following first vaccination. Results showed high titres in the cases of booster with inactivated vaccine. In all cases, however, detectable antibody titres declined quickly.

  14. Adjuvanticity of a CTLA-4 3' UTR complementary oligonucleotide for emulsion formulated recombinant subunit and inactivated vaccines.

    Science.gov (United States)

    Li, Xin; Yang, Lei; Zhao, Peiyan; Yao, Yun; Lu, Fangjie; Tu, Liqun; Liu, Jiwei; Li, Zhiqin; Yu, Yongli; Wang, Liying

    2017-04-25

    Cytotoxic T-lymphocyte antigen 4 (CTLA-4) is recognized as a critical inhibitory regulator of T-cell proliferation and activation, opposing the action of CD28-mediated co-stimulation. Interfering or blocking CTLA-4 can result in continuous T-cell activation required for the full immune response to pathogenic microbes and vaccines. To test if nucleic acid-based CTLA-4 inhibitors could be developed into a novel adjuvant, we designed two oligonucleotides, CMD-1 and CMD-2, with the sequences complementary to the conserve regions identical between human and mouse CTLA-4 mRNA 3' untranslated region (3' UTR), and tested their in vitro effects on CTLA-4 production and their adjuvanticity for vaccines in mice. We found that CMD-1 inhibited the antigen-induced CTLA-4 up-regulation on the CD4 + T cells by interfering its mRNA expression, maintained higher levels of CD80 and CD86 on the CD11c + cells and promoted the recalled proliferation of the CD4 + T cells and CD19 + B cells, and that the CMD-1 enhanced the antibody response against recombinant PCV2b capsid protein or inactivated foot-and-mouth disease virus in both ICR and BALB/c mice. These data suggest that the CMD-1 could be used as a novel vaccine adjuvant capable of inhibiting inhibitory signals rather than inducing stimulatory signals of immune cells. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Evidence of pestivirus RNA in human virus vaccines.

    Science.gov (United States)

    Harasawa, R; Tomiyama, T

    1994-01-01

    We examined live virus vaccines against measles, mumps, and rubella for the presence of pestivirus RNA or of pestiviruses by reverse transcription PCR. Pestivirus RNA was detected in two measles-mumps-rubella combined vaccines and in two monovalent vaccines against mumps and rubella. Nucleotide sequence analysis of the PCR products indicated that a modified live vaccine strain used for immunization of cattle against bovine viral diarrhea is not responsible for the contamination of the vaccines. Images PMID:8077414

  16. FMD virus type Asia-1 irradiated vaccine and evaluation of immune response on guinea-pig model

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    Farahnaz Motamedi-Sedeh

    2017-09-01

    Full Text Available Introduction: Foot and Mouth Disease (FMD is the most contagious disease in cloven-hoofed animals which causes a lot of economical losses. FMD virus belongs to Picornaviridae family and Aphthovirus genus. The aim of the study is evaluation of humoral and cellular immune responses triggered by a Gamma-irradiated FMD vaccine in the guinea-pig model. Materials and Methods: FMD virus type Asia-1 was multiplied on BHK21 cell line and irradiated by gamma ray in different doses. According  to dose/survival curve, D10 value and optimum dose of virus inactivation were calculated 7.69 and 50 kGy, respectively. Antigenic characteristic of irradiated and un-irradiated virus samples were evaluated by complement fixation test (CF test and safety test was done by four blind passages cell culture on IBRS2 cell line. The inactivated virus sample was formulated as Radio- vaccine and immune responses were evaluated in three groups of ginea-pigs; the first group Radio-vaccine, the second group conventional vaccine and the last one was negative control. Results: The results of neutralizing antibody titration for two vaccinated groups were significant (P

  17. Inactivation of internalized and surface contaminated enteric viruses in green onions.

    Science.gov (United States)

    Hirneisen, Kirsten A; Kniel, Kalmia E

    2013-09-02

    With increasing outbreaks of gastroenteritis associated with produce, it is important to assess interventions to reduce the risk of illness. UV, ozone and high pressure are non-thermal processing technologies that have potential to inactivate human pathogens on produce and allow the retention of fresh-like organoleptic properties. The objective of this study was to determine if UV, ozone, and high pressure are effective technologies compared to traditional chlorine spray on green onions to reduce enteric viral pathogens and to determine the effect of location of the virus (surface or internalized) on the efficacy of these processes. Mature green onion plants were inoculated with murine norovirus (MNV), hepatitis A virus (HAV) and human adenovirus type 41 (Ad41) either on the surface through spot inoculation or through inoculating contaminated hydroponic solution allowing for uptake of the virus into the internal tissues. Inoculated green onions were treated with UV (240 mJ s/cm(2)), ozone (6.25 ppm for 10 min), pressure (500 MPa, for 5 min at 20°C), or sprayed with calcium hypochlorite (150 ppm, 4°C). Viral inactivation was determined by comparing treated and untreated inoculated plants using cell culture infectivity assays. Processing treatments were observed to greatly affect viral inactivation. Viral inactivation for all three viruses was greatest after pressure treatment and the lowest inactivation was observed after chlorine and UV treatment. Both surface inoculated viruses and viruses internalized in green onions were inactivated to some extent by these post-harvest processing treatments. These results suggest that ozone and high pressure processes aimed to reduce the level of microbial contamination of produce have the ability to inactivate viruses if they become localized in the interior portions of produce. © 2013.

  18. 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.

  19. Cross-protection induced by Japanese encephalitis vaccines against different genotypes of Dengue viruses in mice.

    Science.gov (United States)

    Li, Jieqiong; Gao, Na; Fan, Dongying; Chen, Hui; Sheng, Ziyang; Fu, Shihong; Liang, Guodong; An, Jing

    2016-01-28

    Dengue viruses (DENVs) and Japanese encephalitis virus (JEV) are closely related mosquito-borne flaviviruses that cause very high global disease burdens. Although cross-reactivity and cross-protection within flaviviruses have been demonstrated, the effect of JEV vaccination on susceptibility to DENV infection has not been well elucidated. In this study, we found that vaccination with the JEV inactivated vaccine (INV) and live attenuated vaccine (LAV) could induce cross-immune responses and cross-protection against DENV1-4 in mice. Despite the theoretical risk of immune enhancement, no increased mortality was observed in our mouse model. Additionally, low but consistently detectable cross-neutralizing antibodies against DENV2 and DENV3 were also observed in the sera of JEV vaccine-immunized human donors. The results suggested that both JEV-LAV and JEV-INV could elicit strong cross-immunity and protection against DENVs, indicating that inoculation with JEV vaccines may influence the distribution of DENVs in co-circulated areas and that the cross-protection induced by JEV vaccines against DENVs might provide important information in terms of DENV prevention.

  20. Ammonia as an In Situ Sanitizer: Influence of Virus Genome Type on Inactivation.

    Science.gov (United States)

    Decrey, Loïc; Kazama, Shinobu; Kohn, Tamar

    2016-08-15

    Treatment of human excreta and animal manure (HEAM) is key in controlling the spread of persistent enteric pathogens, such as viruses. The extent of virus inactivation during HEAM storage and treatment appears to vary with virus genome type, although the reasons for this variability are not clear. Here, we investigated the inactivation of viruses of different genome types under conditions representative of HEAM storage or mesophilic digestion. The goals were to characterize the influence of HEAM solution conditions on inactivation and to determine the potential mechanisms involved. Specifically, eight viruses representing the four viral genome types (single-stranded RNA [ssRNA], double-stranded RNA [dsRNA], single-stranded DNA [ssDNA], and double-stranded DNA [dsDNA]) were exposed to synthetic solutions with well-controlled temperature (20 to 35°C), pH (8 to 9), and ammonia (NH3) concentrations (0 to 40 mmol liter(-1)). DNA and dsRNA viruses were considerably more resistant than ssRNA viruses, resulting in up to 1,000-fold-longer treatment times to reach a 4-log inactivation. The apparently slower inactivation of DNA viruses was rationalized by the higher stability of DNA than that of ssRNA in HEAM. Pushing the system toward harsher pH (>9) and temperature (>35°C) conditions, such as those encountered in thermophilic digestion and alkaline treatments, led to more consistent inactivation kinetics among ssRNA and other viruses. This suggests that the dependence of inactivation on genome type disappeared in favor of protein-mediated inactivation mechanisms common to all viruses. Finally, we recommend the use of MS2 as a conservative indicator to assess the inactivation of ssRNA viruses and the stable ΦX174 or dsDNA phages as indicators for persistent viruses. Viruses are among the most environmentally persistent pathogens. They can be present in high concentrations in human excreta and animal manure (HEAM). Therefore, appropriate treatment of HEAM is important

  1. Humoral Immune Response Induced by PLGA Micro Particle Coupled Newcastle Disease Virus Vaccine in Chickens

    Directory of Open Access Journals (Sweden)

    Sanganagouda K

    2014-02-01

    Full Text Available This experiment was conducted for evaluating the humoral immune responses induced by Poly Lactide-co-Glycolide Acid (PLGA microspheres coupled inactivated Newcastle Disease Virus (NDV vaccine in comparison to an ‘in-house’ prepared inactivated and a live commercial vaccine. PLG microparticles containing inactivated NDV were prepared by a double emulsion technique based on solvent evaporation method. The size of the NDV coupled PLG microparticles was determined by Electron Microscopy. NDV coupled PLG microparticles were spherical having smooth surface, hollow core inside with no pores on the surface. The experiment was conducted in four groups of chickens (n=15. The encapsulation efficiency of NDV coupled PLG microparticles was determined by protein estimation and HA activity in elute. The mean (± SE size of PLG microspheres was found to be 2.409 ± 0.65 µm. The mean percent of encapsulation efficiency of PLG microspheres coupled to NDV was assessed based on the total protein content and HA activity in elute was found to be 8.03 ± 0.50 and 12.5 ± 0.00, respectively. In conclusion, the results of the experiment showed that PLGA coupled NDV vaccine elicited stronger and prolonged humoral immune response in chickens, in comparison to the other tested vaccines, as assessed by haemagglutination inhibition and enzyme linked immuno sorbent asaay titers.

  2. 9 CFR 113.203 - Feline Panleukopenia Vaccine, Killed Virus.

    Science.gov (United States)

    2010-01-01

    ... susceptibility. (1) A constant virus-varying serum neutralization test in tissue culture using 100 to 300 TCID50... Virus. 113.203 Section 113.203 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... Vaccine, Killed Virus, shall be prepared from virus-bearing cell culture fluids. Only Master Seed which...

  3. 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.

  4. Gamma-irradiated influenza A virus provides adjuvant activity to a co-administered poorly immunogenic SFV vaccine in mice.

    Directory of Open Access Journals (Sweden)

    Rachelle eBabb

    2014-06-01

    Full Text Available Many currently available inactivated vaccines require 'adjuvants' to maximise the protective immune responses generated against the antigens of interest. Recent studies in mice with gamma-irradiated influenza A virus (γ-FLU have shown its superior efficacy compared to other forms of inactivated FLU vaccines and its ability to induce both potent type-I interferon (IFN-I responses and the IFN-I associated partial lymphocyte activation. Commonly, IFN-I responses induced by adjuvants, combined in vaccine preparations, have been shown to effectively enhance the immunogenicity of the antigens of interest. Therefore, we investigated the potential adjuvant activity of γ-FLU and the possible effect on antibody responses against co-administrated antigens, using gamma-irradiated Semliki Forest Virus (γ-SFV as the experimental vaccine in mice. Our data show that co-vaccination with γ-FLU and γ-SFV resulted in enhanced SFV-specific antibody responses in terms of increased titres by 6 fold and greater neutralisation efficacy, when compared to vaccination with γ-SFV alone. This study provides promising evidence related to the possible use of γ-FLU as an adjuvant to poorly immunogenic vaccines without compromising the vaccine efficacy of γ-FLU.

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

    Directory of Open Access Journals (Sweden)

    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

  6. The affect of infectious bursal disease virus on avian influenza virus vaccine efficacy

    Science.gov (United States)

    Immunosuppressive viruses are known to affect vaccinal immunity, however the impact of virally induced immunosuppression on avian influenza vaccine efficacy has not been quantified. In order to determine the effect of exposure to infectious bursal disease virus (IBDV) on vaccinal immunity to highly ...

  7. 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.

    Science.gov (United States)

    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

  8. 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.

  9. Introduction of Inactivated Poliovirus Vaccine and Impact on Vaccine-Associated Paralytic Poliomyelitis - Beijing, China, 2014-2016.

    Science.gov (United States)

    Zhao, Dan; Ma, Rui; Zhou, Tao; Yang, Fan; Wu, Jin; Sun, Hao; Liu, Fang; Lu, Li; Li, Xiaomei; Zuo, Shuyan; Yao, Wei; Yin, Jian

    2017-12-15

    When included in a sequential polio vaccination schedule, inactivated polio vaccine (IPV) reduces the risk for vaccine-associated paralytic poliomyelitis (VAPP), a rare adverse event associated with receipt of oral poliovirus vaccine (OPV). During January 2014, the World Health Organization (WHO) recommended introduction of at least 1 IPV dose into routine immunization schedules in OPV-using countries (1). The Polio Eradication and Endgame Strategic Plan 2013-2018 recommended completion of IPV introduction in 2015 and globally synchronized withdrawal of OPV type 2 in 2016 (2). Introduction of 1 dose of IPV into Beijing's Expanded Program on Immunization (EPI) on December 5, 2014 represented China's first province-wide IPV introduction. Coverage with the first dose of polio vaccine was maintained from 96.2% to 96.9%, similar to coverage with the first dose of diphtheria and tetanus toxoids and pertussis vaccine (DTP) (96.5%-97.2%); the polio vaccine dropout rate (the percentage of children who received the first dose of polio vaccine but failed to complete the series) was 1.0% in 2015 and 0.4% in 2016. The use of 3 doses of private-sector IPV per child decreased from 18.1% in 2014, to 17.4% in 2015, and to 14.8% in 2016. No cases of VAPP were identified during 2014-2016. Successful introduction of IPV into the public sector EPI program was attributed to comprehensive planning, preparation, implementation, robust surveillance for adverse events after immunization (AEFI), and monitoring of vaccination coverage. This evaluation provided information that helped contribute to the expansion of IPV use in China and in other OPV-using countries.

  10. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  12. Immune Serum From Sabin Inactivated Poliovirus Vaccine Immunization Neutralizes Multiple Individual Wild and Vaccine-Derived Polioviruses.

    Science.gov (United States)

    Sun, Mingbo; Li, Changgui; Xu, Wenbo; Liao, Guoyang; Li, Rongcheng; Zhou, Jian; Li, Yanping; Cai, Wei; Yan, Dongmei; Che, Yanchun; Ying, Zhifang; Wang, Jianfeng; Yang, Huijuan; Ma, Yan; Ma, Lei; Ji, Guang; Shi, Li; Jiang, Shude; Li, Qihan

    2017-05-15

    A Sabin strain-based inactivated poliomyelitis vaccine (Sabin-IPV) is the rational option for completely eradicating poliovirus transmission. The neutralizing capacity of Sabin-IPV immune serum to different strains of poliovirus is a key indicator of the clinical protective efficacy of this vaccine. Sera collected from 500 infants enrolled in a randomized, blinded, positive control, phase 2 clinical trial were randomly divided into 5 groups: Groups A, B, and C received high, medium, and low doses, respectively, of Sabin-IPV, while groups D and E received trivalent oral polio vaccine and Salk strain-based IPV, respectively, all on the same schedule. Immune sera were collected after the third dose of primary immunization, and tested in cross-neutralization assays against 19 poliovirus strains of all 3 types. All immune sera from all 5 groups interacted with the 19 poliovirus strains with various titers and in a dose-dependent manner. One type 2 immunodeficiency-associated vaccine-derived poliovirus strain was not recognized by these immune sera. Sabin-IPV vaccine can induce protective antibodies against currently circulating and reference wild poliovirus strains and most vaccine-derived poliovirus strains, with rare exceptions. NCT01056705. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  13. Ebola Virus Vaccines – reality or fiction?

    Science.gov (United States)

    Mire, Chad E.; Geisbert, Thomas W.; Feldmann, Heinz

    2016-01-01

    For 40 years ebolaviruses have been responsible for sporadic outbreaks of severe and often fatal hemorrhagic fever in humans and nonhuman primates. In December 2013 an unprecedented Zaire ebolavirus epidemic began in West Africa. Although “patient zero” has finally been reached after 2 years, the virus is again causing disease in the region. Currently there are no licensed vaccines or therapeutic countermeasures against ebolaviruses; however, the epidemic in West Africa has focused attention on the potential vaccine platforms developed over the past 15 years. There has been remarkable progress using a variety of platforms including DNA, subunit, and several viral vector approaches, replicating and non-replicating, which have shown varying degrees of protective efficacy in the “gold-standard” nonhuman primate models for Ebolavirus infections. A number of these vaccine platforms have moved into clinical trials over the past year with the hope of finding an efficacious vaccine to prevent future outbreaks/epidemics of Ebola hemorrhagic fever on the scale of the West African epidemic. PMID:27078187

  14. Interference of Infectious Bursal Diseases (IBD) Virus and Vaccine ...

    African Journals Online (AJOL)

    The interference of Infectious bursal disease (IBD) virus and vaccine with the immune response of the grey brested guinea fowl (Numida meleagridis galeata palas) to Newcastle desease (ND) “LaSota” vaccine was studied using hemagglutination inhibition (HI) test for detection of ND virus antibody and agar gel ...

  15. Control of Influenza and Poliomyelitis with Killed Virus Vaccines

    Science.gov (United States)

    Salk, Jonas; Salk, Darrell

    1977-01-01

    Discusses control of poliomyelitis and influenza by live and killed virus vaccines. Considered are the etiological agents, pathogenic mechanisms and epidemiology of each disease. Reviews recent scientific studies of the diseases. Recommends use of killed virus vaccines in controlling both diseases. (CS)

  16. Chikungunya virus and prospects for a vaccine

    Science.gov (United States)

    Weaver, Scott C; Osorio, Jorge E; Livengood, Jill A; Chen, Rubing; Stinchcomb, Dan T

    2013-01-01

    In 2004, chikungunya virus (CHIKV) re-emerged from East Africa to cause devastating epidemics of debilitating and often chronic arthralgia that have affected millions of people in the Indian Ocean Basin and Asia. More limited epidemics initiated by travelers subsequently occurred in Italy and France, as well as human cases exported to most regions of the world, including the Americas where CHIKV could become endemic. Because CHIKV circulates during epidemics in an urban mosquito–human cycle, control of transmission relies on mosquito abatement, which is rarely effective. Furthermore, there is no antiviral treatment for CHIKV infection and no licensed vaccine to prevent disease. Here, we discuss the challenges to the development of a safe, effective and affordable chikungunya vaccine and recent progress toward this goal. PMID:23151166

  17. Progression of rabbit haemorrhagic disease virus 2 upon vaccination in an industrial rabbitry: a laboratorial approach

    Directory of Open Access Journals (Sweden)

    C.L. Carvalho

    2017-03-01

    Full Text Available Rabbit haemorrhagic disease virus 2 (RHDV2 emerged recently in several European countries, leading to extensive economic losses in the industry. In response to this new infection, specific inactivated vaccines were developed in Europe and full and rapid setup of protective immunity induced by vaccination was reported. However, data on the efficacy of these vaccines in an ongoing-infection scenario is unavailable. In this study we investigated an infected RHDV2 indoor industrial meat rabbitry, where fatalities continued to occur after the implementation of the RHDV2 vaccination, introduced to control the disease. The aim of this study was to understand if these mortalities were RHDV2-related, to discover if the dead animals showed any common features such as age or time distance from vaccination, and to identify the source of the outbreak. Anatomo-pathological analysis of vaccinated animals with the virus showed lesions compatible with systemic haemorrhagic disease and RHDV2-RNA was detected in 85.7% of the animals tested. Sequencing of the vp60 gene amplified from liver samples led to the recognition of RHDV2 field strains demonstrating that after the implementation of vaccination, RHDV2 continued to circulate in the premises and to cause sporadic deaths. A nearby, semi-intensive, RHDV2 infected farm belonging to the same owner was identified as the most probable source of the virus. The main risk factors for virus introduction in these two industries were identified. Despite the virus being able to infect a few of the vaccinated rabbits, the significant decrease in mortality rate observed in vaccinated adult rabbits clearly reflects the efficacy of the vaccination. Nonetheless, the time taken to control the infection also highlights the importance of RHDV2 vaccination prior to the first contact with the virus, highly recommendable in endemic areas, to mitigate the infection’s impact on the industry.

  18. Hepatitis B Virus Vaccine: The Nigerian Story | Odusanya | Journal ...

    African Journals Online (AJOL)

    Hepatitis B (HBV) virus in endemic in Nigeria. Infection is acquired mainly in childhood through horizontal transmission. The infection is preventable by vaccination. Universal childhood vaccination against the infection started in Nigeria less than ten years. Hepatitis B vaccine coverage in Nigeria is 41%, though now it has ...

  19. Kunjin replicon-based simian immunodeficiency virus gag vaccines

    NARCIS (Netherlands)

    Anruka, I.; Mokhonov, V.; Rattanasena, P.; Mokhonova, E.; Leung, J.Y.; Pijlman, G.P.; Cara, A.; Schroder, W.A.; Khromykh, A.A.; Suhrbier, A.

    2008-01-01

    An RNA-based, non-cytopathic replicon vector system, based on the flavivirus Kunjin, has shown considerable promise as a new vaccine delivery system. Here we describe the testing in mice of four different SIVmac239 gag vaccines delivered by Kunjin replicon virus-like-particles. The four vaccines

  20. Optimal Use of Vaccines for Control of Influenza A Virus in Swine

    Science.gov (United States)

    Sandbulte, Matthew R.; Spickler, Anna R.; Zaabel, Pamela K.; Roth, James A.

    2015-01-01

    Influenza A virus in swine (IAV-S) is one of the most important infectious disease agents of swine in North America. In addition to the economic burden of IAV-S to the swine industry, the zoonotic potential of IAV-S sometimes leads to serious public health concerns. Adjuvanted, inactivated vaccines have been licensed in the United States for over 20 years, and there is also widespread usage of autogenous/custom IAV-S vaccines. Vaccination induces neutralizing antibodies and protection against infection with very similar strains. However, IAV-S strains are so diverse and prone to mutation that these vaccines often have disappointing efficacy in the field. This scientific review was developed to help veterinarians and others to identify the best available IAV-S vaccine for a particular infected herd. We describe key principles of IAV-S structure and replication, protective immunity, currently available vaccines, and vaccine technologies that show promise for the future. We discuss strategies to optimize the use of available IAV-S vaccines, based on information gathered from modern diagnostics and surveillance programs. Improvements in IAV-S immunization strategies, in both the short term and long term, will benefit swine health and productivity and potentially reduce risks to public health. PMID:26344946

  1. Optimal Use of Vaccines for Control of Influenza A Virus in Swine

    Directory of Open Access Journals (Sweden)

    Matthew R. Sandbulte

    2015-01-01

    Full Text Available Influenza A virus in swine (IAV-S is one of the most important infectious disease agents of swine in North America. In addition to the economic burden of IAV-S to the swine industry, the zoonotic potential of IAV-S sometimes leads to serious public health concerns. Adjuvanted, inactivated vaccines have been licensed in the United States for over 20 years, and there is also widespread usage of autogenous/custom IAV-S vaccines. Vaccination induces neutralizing antibodies and protection against infection with very similar strains. However, IAV-S strains are so diverse and prone to mutation that these vaccines often have disappointing efficacy in the field. This scientific review was developed to help veterinarians and others to identify the best available IAV-S vaccine for a particular infected herd. We describe key principles of IAV-S structure and replication, protective immunity, currently available vaccines, and vaccine technologies that show promise for the future. We discuss strategies to optimize the use of available IAV-S vaccines, based on information gathered from modern diagnostics and surveillance programs. Improvements in IAV-S immunization strategies, in both the short term and long term, will benefit swine health and productivity and potentially reduce risks to public health.

  2. Progress in Developing Virus-like Particle Influenza Vaccines

    Science.gov (United States)

    Quan, Fu-Shi; Lee, Young-Tae; Kim, Ki-Hye; Kim, Min-Chul; Kang, Sang-Moo

    2016-01-01

    Summary Recombinant vaccines based on virus-like particles (VLPs) or nanoparticles have been successful in their safety and efficacy in preclinical and clinical studies. The technology of expressing enveloped VLP vaccines has combined with molecular engineering of proteins in membrane-anchor and immunogenic forms mimicking the native conformation of surface proteins on the enveloped viruses. This review summarizes recent developments in influenza VLP vaccines against seasonal, pandemic, and avian influenza viruses from the perspective of use in humans. The immunogenicity and efficacies of influenza VLP vaccine in the homologous and cross-protection were reviewed. Discussions include limitations of current influenza vaccination strategies and future directions to confer broadly cross protective new influenza vaccines as well as vaccination. PMID:27058302

  3. Engineering attenuated virus vaccines by controlling replication fidelity.

    Science.gov (United States)

    Vignuzzi, Marco; Wendt, Emily; Andino, Raul

    2008-02-01

    Long-lasting protection against viral infection is best achieved by vaccination with attenuated viruses. Obtaining stably attenuated vaccine strains has traditionally been an empirical process, which greatly restricts the number of effective vaccines for viral diseases. Here we describe a rational approach for engineering stably attenuated viruses that can serve as safe and effective vaccines. Our approach exploits the observation that restricting viral population diversity by increasing replication fidelity greatly reduces viral tissue tropism and pathogenicity. We show that poliovirus variants with reduced genetic diversity elicit a protective immune response in an animal model of infection. Indeed, these novel vaccine candidates are comparable in efficacy to the currently available Sabin type 1 vaccine strain, but have the added advantage of being more stable, as their increased replication fidelity prevents reversion to the pathogenic wild-type phenotype. We propose that restricting viral quasispecies diversity provides a general approach for the rational design of stable, attenuated vaccines for a wide variety of viruses.

  4. Overcoming maternal antibody interference by vaccination with human adenovirus 5 recombinant viruses expressing the hemagglutinin and the nucleoprotein of swine influenza virus.

    Science.gov (United States)

    Wesley, Ronald D; Lager, Kelly M

    2006-11-26

    Sows and gilts lack immunity to human adenovirus 5 (Ad-5) vectored vaccines so immunogens of swine pathogens can be expressed with these vaccines in order to immunize suckling piglets that have interfering, maternally derived antibodies. In this study 7-day-old piglets, that had suckled H3N2 infected gilts, were sham-inoculated with a non-expressing Ad-5 vector or given a primary vaccination with replication-defective Ad-5 viruses expressed the H3 hemagglutinin and the nucleoprotein of swine influenza virus (SIV) subtype H3N2. The hemagglutination inhibition (HI) titer of the sham-inoculated group (n = 12) showed continued antibody decay whereas piglets vaccinated with Ad-5 SIV (n = 23) developed an active immune response by the second week post-vaccination. At 4 weeks-of-age when the HI titer of the sham-inoculated group had decayed to 45, the sham-inoculated group and half of the Ad-5 SIV vaccinated pigs were boosted with a commercial inactivated SIV vaccine. The boosted pigs that had been primed in the presence of maternal interfering antibodies had a strong anamnestic response while sham-inoculated pigs did not respond to the commercial vaccine. Two weeks after the booster vaccination the pigs were challenged with a non-homologous H3N2 virulent SIV. The efficacy of the vaccination protocol was demonstrated by abrogation of clinical signs, by clearance of challenge virus from pulmonary lavage fluids, by markedly reduced virus shedding in nasal secretions, and by the absence of moderate or severe SIV-induced lung lesions. These recombinant Ad-5 SIV vaccines are useful for priming the immune system to override the effects of maternally derived antibodies which interfere with conventional SIV vaccines.

  5. A propagation model of computer virus with nonlinear vaccination probability

    Science.gov (United States)

    Gan, Chenquan; Yang, Xiaofan; Liu, Wanping; Zhu, Qingyi

    2014-01-01

    This paper is intended to examine the effect of vaccination on the spread of computer viruses. For that purpose, a novel computer virus propagation model, which incorporates a nonlinear vaccination probability, is proposed. A qualitative analysis of this model reveals that, depending on the value of the basic reproduction number, either the virus-free equilibrium or the viral equilibrium is globally asymptotically stable. The results of simulation experiments not only demonstrate the validity of our model, but also show the effectiveness of nonlinear vaccination strategies. Through parameter analysis, some effective strategies for eradicating viruses are suggested.

  6. Inactivation of human immunodeficiency virus (HIV) by ionizing radiation in body fluids and serological evidence

    International Nuclear Information System (INIS)

    Bigbee, P.D.; Sarin, P.S.; Humphreys, J.C.; Eubanks, W.G.; Sun, D.; Hocken, D.G.; Thornton, A.; Adams, D.E.; Simic, M.G.

    1989-01-01

    A method to use ionizing radiation to inactivate HIV (Human Immunodeficiency Virus) in human body fluids was studied in an effort to reduce the risk of accidental infection to forensic science laboratory workers. Experiments conducted indicate that an X-ray absorbed dose of 25 krad was required to completely inactivate HIV. This does not alter forensically important constituents such as enzymes and proteins in body fluids. This method of inactivation of HIV cannot be used on body fluids which will be subjected to deoxyribonucleic acid (DNA) typing

  7. Selective inactivation of human immunodeficiency virus with subpicosecond near-infrared laser pulses

    International Nuclear Information System (INIS)

    Tsen, K T; Tsen, S-W D; Hung, C-F; Wu, T-C; Kiang, Juliann G

    2008-01-01

    We demonstrate for the first time that human immunodeficiency virus (HIV) can be inactivated by irradiation with subpicosecond near-infrared laser pulses at a moderate laser power density. By comparing the threshold laser power density for the inactivation of HIV with those of human red blood cells and mouse dendritic cells, we conclude that it is plausible to use the ultrashort pulsed laser to selectively inactivate blood-borne pathogens such as HIV while leaving sensitive materials like human red blood cells unharmed. This finding has important implications in the development of a new laser technology for disinfection of viral pathogens in blood products and in the clinic. (fast track communication)

  8. FAST TRACK COMMUNICATION: Inactivation of viruses with a very low power visible femtosecond laser

    Science.gov (United States)

    Tsen, K. T.; Tsen, Shaw-Wei D.; Chang, Chih-Long; Hung, Chien-Fu; Wu, T.-C.; Kiang, Juliann G.

    2007-08-01

    We demonstrate for the first time that, by using a visible femtosecond laser, it is effective to inactivate viruses such as bacteriophage M13 through impulsive stimulated Raman scattering. By using a very low power visible femtosecond laser having a wavelength of 425 nm and a pulse width of 100 fs, we show that M13 phages were inactivated when the laser power density was greater than or equal to 50 MW cm-2. The inactivation of M13 phages was determined by plaque counts and depended on the pulse width as well as power density of the excitation laser.

  9. Inactivation of viruses with a very low power visible femtosecond laser

    Energy Technology Data Exchange (ETDEWEB)

    Tsen, K T [Department of Physics, Arizona State University, Tempe, AZ 85287 (United States); Tsen, Shaw-Wei D [Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD 21231 (United States); Chang, C.-L. [Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD 21231 (United States); Hung, C.-F. [Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD 21231 (United States); Wu, T-C [Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD 21231 (United States); Kiang, Juliann G [Scientific Research Department, Armed Forces Radiobiology Research Institute, Uniformed Services University of The Health Sciences, Bethesda, MD 20889-5603 (United States)

    2007-08-15

    We demonstrate for the first time that, by using a visible femtosecond laser, it is effective to inactivate viruses such as bacteriophage M13 through impulsive stimulated Raman scattering. By using a very low power visible femtosecond laser having a wavelength of 425 nm and a pulse width of 100 fs, we show that M13 phages were inactivated when the laser power density was greater than or equal to 50 MW cm{sup -2}. The inactivation of M13 phages was determined by plaque counts and depended on the pulse width as well as power density of the excitation laser. (fast track communication)

  10. Inactivation strategy for pseudorabies virus in milk for production of biopharmaceuticals.

    Science.gov (United States)

    Chang, Jen-Ting; Chou, Yu-Chi; Lin, Meng-Shiue; Wang, Shih-Rong

    2010-11-01

    By selecting pseudorabies virus (PrV) as a model virus, this study assessed the feasibility of applying viral inactivation strategies to manufacturing medicinal products from the milk of transgenic sows. The efficacy of heat, acidic/alkaline and detergent treatments was also evaluated with respect to their ability to inactivate PrV in milk samples. Experimental results indicate that PrV was inactivated obviously at least 7.125 log10 for 30 min at 60 degrees C. At alkaline values of pH 10 and acidic value of pH 4, PrV infectivity was reduced to 3.625 log10 and exceeded 5 log10, respectively. Moreover, PrV virus was inactivated efficiently (> 3.875 log10) by using 0.25-1% of Triton X-100 treatment and without a loss of biological activity of the recombinant human coagulation factor IX (rhFIX). of this study demonstrate the effectiveness of the proposed detergent inactivation method for PrV inactivation of rhFIX production from transgenic products, especially in milk materials.

  11. Buffer AVL Alone Does Not Inactivate Ebola Virus in a Representative Clinical Sample Type.

    Science.gov (United States)

    Smither, Sophie J; Weller, Simon A; Phelps, Amanda; Eastaugh, Lin; Ngugi, Sarah; O'Brien, Lyn M; Steward, Jackie; Lonsdale, Steve G; Lever, Mark S

    2015-10-01

    Rapid inactivation of Ebola virus (EBOV) is crucial for high-throughput testing of clinical samples in low-resource, outbreak scenarios. The EBOV inactivation efficacy of Buffer AVL (Qiagen) was tested against marmoset serum (EBOV concentration of 1 × 10(8) 50% tissue culture infective dose per milliliter [TCID50 · ml(-1)]) and murine blood (EBOV concentration of 1 × 10(7) TCID50 · ml(-1)) at 4:1 vol/vol buffer/sample ratios. Posttreatment cell culture and enzyme-linked immunosorbent assay (ELISA) analysis indicated that treatment with Buffer AVL did not inactivate EBOV in 67% of samples, indicating that Buffer AVL, which is designed for RNA extraction and not virus inactivation, cannot be guaranteed to inactivate EBOV in diagnostic samples. Murine blood samples treated with ethanol (4:1 [vol/vol] ethanol/sample) or heat (60°C for 15 min) also showed no viral inactivation in 67% or 100% of samples, respectively. However, combined Buffer AVL and ethanol or Buffer AVL and heat treatments showed total viral inactivation in 100% of samples tested. The Buffer AVL plus ethanol and Buffer AVL plus heat treatments were also shown not to affect the extraction of PCR quality RNA from EBOV-spiked murine blood samples. © Crown copyright 2015.

  12. Photodynamic inactivation of rubella virus enhances recombination with a latent virus of a baby hamster kidney cell line BHK21

    Energy Technology Data Exchange (ETDEWEB)

    Yamamoto, Nobuto; Urade, Masahiro (Hahnemann Univ. School of Medicine, Philadelphia, PA (USA))

    1989-09-01

    Rubella virus is very sensitive to photodynamic action. When tested with 1.2 x 10{sup -5} M toluidine blue and 8 W fluorescent lamp at a fluence of 11 W/m{sup 2}, inactivation kinetics showed a linear single hit curve with a k value of 1.48 min{sup -1}. Photodynamic inactivation of rubella virus greatly enhanced recombination with a latent virus (R-virus) of baby hamster kidney BHK21 cells. In contrast, no hybrids were detected in lysates of the cells infected with either UV-treated or untreated rubella virus. Therefore, hybrid viruses were readily detected only in lysates of BHK21 cells infected with photodynamically treated rubella virus. Photodynamic damage of rubella virus genomes generated a new hybrid type (hybrid type 3) in addition to a previously described type 2 hybrid (formerly designated as HPV-RV variant). Although both of these hybrid types carry the CF antigens of rubella virus, plaque forming ability of type 3 hybrid is neutralized neither by anti-rubella serum nor by anti-latent virus serum while type 2 hybrid is neutralized by anti-latent virus serum. (author).

  13. Photodynamic inactivation of rubella virus enhances recombination with a latent virus of a baby hamster kidney cell line BHK21

    International Nuclear Information System (INIS)

    Yamamoto, Nobuto; Urade, Masahiro

    1989-01-01

    Rubella virus is very sensitive to photodynamic action. When tested with 1.2 x 10 -5 M toluidine blue and 8 W fluorescent lamp at a fluence of 11 W/m 2 , inactivation kinetics showed a linear single hit curve with a k value of 1.48 min -1 . Photodynamic inactivation of rubella virus greatly enhanced recombination with a latent virus (R-virus) of baby hamster kidney BHK21 cells. In contrast, no hybrids were detected in lysates of the cells infected with either UV-treated or untreated rubella virus. Therefore, hybrid viruses were readily detected only in lysates of BHK21 cells infected with photodynamically treated rubella virus. Photodynamic damage of rubella virus genomes generated a new hybrid type (hybrid type 3) in addition to a previously described type 2 hybrid (formerly designated as HPV-RV variant). Although both of these hybrid types carry the CF antigens of rubella virus, plaque forming ability of type 3 hybrid is neutralized neither by anti-rubella serum nor by anti-latent virus serum while type 2 hybrid is neutralized by anti-latent virus serum. (author)

  14. Inactivation of human T-cell lymphotropic virus, type III by heat, chemicals, and irradiation

    International Nuclear Information System (INIS)

    Quinnan, G.V. Jr.; Wells, M.A.; Wittek, A.E.; Phelan, M.A.; Mayner, R.E.; Feinstone, S.; Purcell, R.H.; Epstein, J.S.

    1986-01-01

    Infectivity of human T-cell lymphotropic virus, Type III (HTLV-III) was inactivated by heat more rapidly if in liquid medium than if lyophilized and more rapidly at 60 than 56 0 C. When HTLV-III was added to factor VIII suspension, then lyophilized and heated at 60 0 C for 2 hours or longer there was elimination of 1 X 10(6) in vitro infectious units (IVIU) of virus. Much of the viral inactivation appeared to result from lyophilization. The application of water-saturated chloroform to the lyophilized material containing virus also resulted in elimination of infectivity. HTLV-III was efficiently inactivated by formalin, beta-propiolactone, ethyl ether, detergent, and ultraviolet light plus psoralen. The results are reassuring regarding the potential safety of various biological products

  15. 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...

  16. Comparison of protection from homologous cell-free vs cell-associated SIV challenge afforded by inactivated whole SIV vaccines.

    NARCIS (Netherlands)

    J.L. Heeney (Jonathan); P. de Vries (Petra); R. Dubbes (Rob); W. Koornstra (Willem); H. Niphuis; P. ten Haaft (Peter); J. Boes (Jolande); M.E.M. Dings (Marlinda); B. Morein (Bror); A.D.M.E. Osterhaus (Albert)

    1992-01-01

    textabstractThis study attempted to determine if SIV vaccines could protect against challenge with peripheral blood mononuclear cells (PBMCs) from an SIV infected rhesus monkey. Mature Macaca mulatta were vaccinated four times with formalin inactivated SIVmac32H administered in MDP adjuvant (n = 8)

  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. Application of solid-phase radioimmunoassay in determining antibodies to Aujeszky's disease virus in blood serum of vaccinated pigs

    Energy Technology Data Exchange (ETDEWEB)

    Rodak, L.; Smid, B.; Valicek, L. (Vyzkumny Ustav Veterinarniho Lekarstvi, Brno-Medlanky (Czechoslovakia))

    1983-11-01

    In the blood sera of pigs vaccinated with inactivated vaccines manufactured by three different manufacturers the RIA method was used to determine the specific antibodies to the virus of Aujeszky's disease. In certain groups of vaccinated pigs the results of the RIA examination are unfavourably affected by the bond of antibodies to the cellular antigenous determinants. This proves that following vaccination antibodies are formed not only against the viral antigen but also against the antigens of cells on which the vaccination virus is propagated. These shortcomings are eliminated by the use of suitable cellular cultures for the preparation of viral and control antigens. Antigens are applicable for RIA and for ELISA examinations of blood sera of infected and vaccinated pigs. The advantages are described of the RIA and ELISA methods as compared with the virus neutralization test.

  19. Differences in female-male mortality after high-titre measles vaccine and association with subsequent vaccination with diphtheria-tetanus-pertussis and inactivated poliovirus

    DEFF Research Database (Denmark)

    Aaby, Peter; Jensen, Henrik; Samb, Badara

    2003-01-01

    Females given high-titre measles vaccine (HTMV) have high mortality; diphtheria-tetanus-pertussis (DTP) vaccination might be associated with increased female mortality. We aimed to assess whether DTP or inactivated poliovirus (IPV) administered after HTMV was associated with increased female...

  20. Emergency postexposure vaccination with vesicular stomatitis virus-vectored Ebola vaccine after needlestick.

    Science.gov (United States)

    Lai, Lilin; Davey, Richard; Beck, Allison; Xu, Yongxian; Suffredini, Anthony F; Palmore, Tara; Kabbani, Sarah; Rogers, Susan; Kobinger, Gary; Alimonti, Judie; Link, Charles J; Rubinson, Lewis; Ströher, Ute; Wolcott, Mark; Dorman, William; Uyeki, Timothy M; Feldmann, Heinz; Lane, H Clifford; Mulligan, Mark J

    Safe and effective vaccines and drugs are needed for the prevention and treatment of Ebola virus disease, including following a potentially high-risk exposure such as a needlestick. To assess response to postexposure vaccination in a health care worker who was exposed to the Ebola virus. Case report of a physician who experienced a needlestick while working in an Ebola treatment unit in Sierra Leone on September 26, 2014. Medical evacuation to the United States was rapidly initiated. Given the concern about potentially lethal Ebola virus disease, the patient was offered, and provided his consent for, postexposure vaccination with an experimental vaccine available through an emergency Investigational New Drug application. He was vaccinated on September 28, 2014. The vaccine used was VSVΔG-ZEBOV, a replicating, attenuated, recombinant vesicular stomatitis virus (serotype Indiana) whose surface glycoprotein gene was replaced by the Zaire Ebola virus glycoprotein gene. This vaccine has entered a clinical trial for the prevention of Ebola in West Africa. The vaccine was administered 43 hours after the needlestick occurred. Fever and moderate to severe symptoms developed 12 hours after vaccination and diminished over 3 to 4 days. The real-time reverse transcription polymerase chain reaction results were transiently positive for vesicular stomatitis virus nucleoprotein gene and Ebola virus glycoprotein gene (both included in the vaccine) but consistently negative for Ebola virus nucleoprotein gene (not in the vaccine). Early postvaccination cytokine secretion and T lymphocyte and plasmablast activation were detected. Subsequently, Ebola virus glycoprotein-specific antibodies and T cells became detectable, but antibodies against Ebola viral matrix protein 40 (not in the vaccine) were not detected. It is unknown if VSVΔG-ZEBOV is safe or effective for postexposure vaccination in humans who have experienced a high-risk occupational exposure to the Ebola virus, such as a

  1. Hatchability, serology and virus excretion following in ovo vaccination of chickens with an avian metapneumovirus vaccine.

    Science.gov (United States)

    Hess, M; Huggins, M B; Heincz, U

    2004-12-01

    The present investigation describes for the first time the effect of an avian metapneumovirus vaccine administered in ovo to 18-day-old chicken embryos. The application of the vaccine had no adverse effect on the hatchability or the health of the chicks post hatch. The antibody titres achieved were higher than those determined for birds vaccinated at 1 day old. Not only were the mean titres in the in ovo vaccinated groups higher, but many more birds developed a measurable antibody response than birds vaccinated at 1 day old. Variation of the vaccine dose used in ovo had little effect on the serological responses that peaked 21 to 28 days post hatch. Re-isolation of the vaccine virus was much more successful from birds vaccinated in ovo than from birds vaccinated at 1 day old, and detection of the nucleic acid by polymerase chain reaction correlated with the results of live virus isolation.

  2. Delayed vaccine virus replication in chickens vaccinated subcutaneously with an immune complex infectious bursal disease vaccine: Quantification of vaccine virus by real-time polymerase chain reaction

    OpenAIRE

    Iván, Judit; Velhner, Maja; Ursu, Krisztina; Germán, Péter; Mató, Tamás; Drén, Csaba Nick; Mészáros, János

    2005-01-01

    The distribution of the immune complex vaccine virus for infectious bursal disease (IBD) in tissue was examined and the viral loads of the organs were quantitatively compared. One-day-old specific pathogen free (SPF) and maternally immune broiler chickens were injected subcutaneously with the vaccine. Lymphoid and non-lymphoid tissues were collected at various time intervals during the experiment to test for infectious bursal disease virus (IBDV)-RNA by using reverse transcriptase-polymerase ...

  3. Effect of manufacturing process parameters on virus inactivation by dry heat treatment at 80 degrees C in factor VIII.

    Science.gov (United States)

    Roberts, P L; Dunkerley, C; McAuley, A; Winkelman, L

    2007-01-01

    Dry heat treatment at 80 degrees C for 72 h is used as a virus inactivation step for some coagulation factor concentrates such as Bio Products Laboratory's (BPL) factor VIII 8Y. In the current study, the effect of this process has been tested on a range of viruses. In addition the effect of various manufacturing process parameters on virus inactivation has been investigated. Samples of product intermediate were obtained from manufacturing, spiked with virus and subjected to freeze drying and dry heat treatment. Virus inactivation was determined by infectivity assay. Freeze drying followed by dry heat treatment was effective for inactivating a wide range of enveloped and nonenveloped viruses. Sucrose or protein concentration had no effect on virus inactivation. Product presentation or the interruption of heat treatment also had no effect. The inactivation of some of the viruses was greater at higher residual water content but under such conditions the stability of the product was reduced. This virus inactivation step was effective for a wide range of viruses and over the range of process conditions encountered in manufacturing. This demonstrates the robustness of this process step.

  4. Evaluation of a genetically modified foot-and-mouth disease virus vaccine candidate generated by reverse genetics

    Science.gov (United States)

    2012-01-01

    Background Foot-and-mouth disease (FMD) is the most economically important and highly contagious disease of cloven-hoofed animals worldwide. Control of the disease has been mainly based on large-scale vaccinations with whole-virus inactivated vaccines. In recent years, a series of outbreaks of type O FMD occurred in China (including Chinese Taipei, Chinese Hong Kong) posed a tremendous threat to Chinese animal husbandry. Its causative agent, type O FMDV, has evolved into three topotypes (East–South Asia (ME-SA), Southeast Asia (SEA), Cathay (CHY)) in these regions, which represents an important obstacle to disease control. The available FMD vaccine in China shows generally good protection against ME-SA and SEA topotype viruses infection, but affords insufficient protection against some variants of the CHY topotype. Therefore, the choice of a new vaccine strain is of fundamental importance. Results The present study describes the generation of a full-length infectious cDNA clone of FMDV vaccine strain and a genetically modified virus with some amino acid substitutions in antigenic sites 1, 3, and 4, based on the established infectious clone. The recombinant viruses had similar growth properties to the wild O/HN/CHA/93 virus. All swine immunized with inactivated vaccine prepared from the O/HN/CHA/93 were fully protected from challenge with the viruses of ME-SA and SEA topotypes and partially protected against challenge with the virus of CHY topotype at 28 days post-immunization. In contrast, the swine inoculated with the genetically modified vaccine were completely protected from the infection of viruses of the three topotypes. Conclusions Some amino acid substitutions in the FMDV vaccine strain genome did not have an effect on the ability of viral replication in vitro. The vaccine prepared from genetically modified FMDV by reverse genetics significantly improved the protective efficacy to the variant of the CHY topotype, compared with the wild O/HN/CHA/93 virus

  5. Evaluation of a genetically modified foot-and-mouth disease virus vaccine candidate generated by reverse genetics

    Directory of Open Access Journals (Sweden)

    Li Pinghua

    2012-05-01

    Full Text Available Abstract Background Foot-and-mouth disease (FMD is the most economically important and highly contagious disease of cloven-hoofed animals worldwide. Control of the disease has been mainly based on large-scale vaccinations with whole-virus inactivated vaccines. In recent years, a series of outbreaks of type O FMD occurred in China (including Chinese Taipei, Chinese Hong Kong posed a tremendous threat to Chinese animal husbandry. Its causative agent, type O FMDV, has evolved into three topotypes (East–South Asia (ME-SA, Southeast Asia (SEA, Cathay (CHY in these regions, which represents an important obstacle to disease control. The available FMD vaccine in China shows generally good protection against ME-SA and SEA topotype viruses infection, but affords insufficient protection against some variants of the CHY topotype. Therefore, the choice of a new vaccine strain is of fundamental importance. Results The present study describes the generation of a full-length infectious cDNA clone of FMDV vaccine strain and a genetically modified virus with some amino acid substitutions in antigenic sites 1, 3, and 4, based on the established infectious clone. The recombinant viruses had similar growth properties to the wild O/HN/CHA/93 virus. All swine immunized with inactivated vaccine prepared from the O/HN/CHA/93 were fully protected from challenge with the viruses of ME-SA and SEA topotypes and partially protected against challenge with the virus of CHY topotype at 28 days post-immunization. In contrast, the swine inoculated with the genetically modified vaccine were completely protected from the infection of viruses of the three topotypes. Conclusions Some amino acid substitutions in the FMDV vaccine strain genome did not have an effect on the ability of viral replication in vitro. The vaccine prepared from genetically modified FMDV by reverse genetics significantly improved the protective efficacy to the variant of the CHY topotype, compared with the

  6. [Recent Advances in Vaccines and Drugs Against the Ebola Virus].

    Science.gov (United States)

    Zhu, Xiang; Yao, Chenguang; Wei, Yanhong; Kou, Zheng; Hu, Kanghong

    2015-05-01

    The Ebola virus belongs to the Filovirus family, which causes Ebola hemorrhagic fever (mortality, 25%-90%). An outbreak of infection by the Ebola virus is sweeping across West Africa, leading to high mortality and worldwide panic. The Ebola virus has caused a serious threat to public health, so intensive scientific studies have been carried out. Several vaccines (e.g., rVSV-ZEBOV, ChAd3-ZEBOV) have been put into clinical trials and antiviral drugs (e.g., TKM-Ebola, ZMAPP) have been administered in the emergency setting to patients infected by the Ebola virus. Here, recent advances in vaccines and drugs against the Ebola virus are reviewed.

  7. Serum-free microcarrier based production of replication deficient Influenza vaccine candidate virus lacking NS1 using Vero cells

    Directory of Open Access Journals (Sweden)

    Yan Mylene L

    2011-08-01

    Full Text Available Abstract Background Influenza virus is a major health concern that has huge impacts on the human society, and vaccination remains as one of the most effective ways to mitigate this disease. Comparing the two types of commercially available Influenza vaccine, the live attenuated virus vaccine is more cross-reactive and easier to administer than the traditional inactivated vaccines. One promising live attenuated Influenza vaccine that has completed Phase I clinical trial is deltaFLU, a deletion mutant lacking the viral Nonstructural Protein 1 (NS1 gene. As a consequence of this gene deletion, this mutant virus can only propagate effectively in cells with a deficient interferon-mediated antiviral response. To demonstrate the manufacturability of this vaccine candidate, a batch bioreactor production process using adherent Vero cells on microcarriers in commercially available animal-component free, serum-free media is described. Results Five commercially available animal-component free, serum-free media (SFM were evaluated for growth of Vero cells in agitated Cytodex 1 spinner flask microcarrier cultures. EX-CELL Vero SFM achieved the highest cell concentration of 2.6 × 10^6 cells/ml, whereas other SFM achieved about 1.2 × 10^6 cells/ml. Time points for infection between the late exponential and stationary phases of cell growth had no significant effect in the final virus titres. A virus yield of 7.6 Log10 TCID50/ml was achieved using trypsin concentration of 10 μg/ml and MOI of 0.001. The Influenza vaccine production process was scaled up to a 3 liter controlled stirred tank bioreactor to achieve a cell density of 2.7 × 10^6 cells/ml and virus titre of 8.3 Log10 TCID50/ml. Finally, the bioreactor system was tested for the production of the corresponding wild type H1N1 Influenza virus, which is conventionally used in the production of inactivated vaccine. High virus titres of up to 10 Log10 TCID50/ml were achieved. Conclusions We describe for the

  8. Protective effect of inactivated hepatitis A vaccine against the outbreak of hepatitis A in an open rural community.

    Science.gov (United States)

    Shen, Yue-Gen; Gu, Xie-Jun; Zhou, Jian-Hong

    2008-05-07

    To evaluate the protective effect of inactivated hepatitis A vaccine (Healive) against hepatitis A outbreak in an emergency vaccination campaign. During an outbreak of hepatitis A in Honghe Town, Xiuzhou District, Jiaxing City, Zhejiang Province, two nonrandomized controlled trials were conducted in September 2006. The first trial was to vaccinate 108 anti-HAV negative individuals with close contacts of the patients from September with 1 dose of an inactivated hepatitis A vaccine, Healive. The control group comprised of 115 individuals with close contacts of the patients before September. The second trial was to vaccinate 3365 primary and secondary school students who volunteered to receive a dose of Healive and 2572 students who did not receive Healive serving as its controls. An epidemiological survey was conducted to evaluate the protective efficacy of the vaccine. A total of 136 hepatitis A cases were reported during an outbreak that started in June, peaked in August and September, and ended after December of 2006. After a massive vaccination of school children in September, the number of cases declined significantly. No hepatitis A was detected in the 108 vaccinated individuals with close contacts of patients, whereas 4 cases of hepatitis A were found in the controls. The infection rate of hepatitis A was not significantly different in the individuals with close contacts of patients whether or not they received the vaccine (P = 0.122). No hepatitis A was detected in the 3365 students who received the vaccine, four cases of hepatitis A were found in the controls. The infection rate of students with or without vaccination was significantly different in the students who received the vaccine (0/3365 vs 4/2572, P = 0.035). The protective efficacy of the vaccine was 100%. Inactivated hepatitis A vaccine demonstrates a good protective effect against an outbreak of hepatitis A.

  9. 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.

  10. A side effect of decreased fertility associated with vaccination against bluetongue virus serotype 8 in Holstein dairy cows.

    Science.gov (United States)

    Nusinovici, Simon; Seegers, Henri; Joly, Alain; Beaudeau, François; Fourichon, Christine

    2011-08-01

    Inactivated virus vaccines have been widely used to control bluetongue after introduction of serotype 8 of the bluetongue virus (BTV) in northern Europe in 2006. To evaluate vaccination, quantitative knowledge of its possible side effects is needed. One current adverse reaction with inactivated vaccines is a rise in body temperature, which could reduce cow reproductive performance. The objective of this study was to quantify a possible side effect of vaccination on fertility before the implantation of the embryo of dairy cows under field conditions. The study was performed on herds that were not exposed to BTV. Fertility was assessed by return-to-service following artificial insemination (AI). Biological assumptions for a possible side effect of vaccination were conception failure and embryonic death. Associations between return-to-service rates and vaccine injections were assessed using mixed-logistic regression models and survival analysis. Two models were considered: a 3-week-return-to-service model comparing cows vaccinated between 3 days before and 16 days after AI and unvaccinated cows (assuming an effect on conception failure or early embryonic death), and a 90-day-return-to-service model comparing cows vaccinated between 3 days before and 42 days after AI and unvaccinated cows (assuming an effect on conception failure, early or late embryonic death). Only cows receiving a second vaccine injection between 2 and 7 days after AI had a significantly higher risk of 3-week-return-to-service (RR=1.19 [1.07-1.33]). This corresponds to an increase of return-to-service by 4 percentage points. A side effect of vaccination could be due to early embryonic death. The slight side effect on fertility associated with vaccination was low compared to effects of BTV-8 exposure on fertility. Copyright © 2011 Elsevier B.V. All rights reserved.

  11. Physicochemical inactivation of Lassa, Ebola, and Marburg viruses and effect on clinical laboratory analyses

    International Nuclear Information System (INIS)

    Mitchell, S.W.; McCormick, J.B.

    1984-01-01

    Clinical specimens from patients infected with Lassa, Ebola, or Marburg virus may present a serious biohazard to laboratory workers. The authors have examined the effects of heat, alteration of pH, and gamma radiation on these viruses in human blood and on the electrolytes, enzymes, and coagulation factors measured in laboratory tests that are important in the care of an infected patient. Heating serum at 60 degrees C for 1 h reduced high titers of these viruses to noninfectious levels without altering the serum levels of glucose, blood urea nitrogen, and electrolytes. Dilution of blood in 3% acetic acid, diluent for a leukocyte count, inactivated all of these viruses. All of the methods tested for viral inactivation markedly altered certain serum proteins, making these methods unsuitable for samples that are to be tested for certain enzyme levels and coagulation factors

  12. Synthetic protocells interact with viral nanomachinery and inactivate pathogenic human virus.

    Directory of Open Access Journals (Sweden)

    Matteo Porotto

    Full Text Available We present a new antiviral strategy and research tool that could be applied to a wide range of enveloped viruses that infect human beings via membrane fusion. We test this strategy on two emerging zoonotic henipaviruses that cause fatal encephalitis in humans, Nipah (NiV and Hendra (HeV viruses. In the new approach, artificial cell-like particles (protocells presenting membrane receptors in a biomimetic manner were developed and found to attract and inactivate henipavirus envelope glycoprotein pseudovirus particles, preventing infection. The protocells do not accumulate virus during the inactivation process. The use of protocells that interact with, but do not accumulate, viruses may provide significant advantages over current antiviral drugs, and this general approach may have wide potential for antiviral development.

  13. Evaluation of enteric-coated tablets as a whole cell inactivated vaccine candidate against Vibrio cholerae.

    Science.gov (United States)

    Fernández, Sonsire; Año, Gemma; Castaño, Jorge; Pino, Yadira; Uribarri, Evangelina; Riverón, Luis A; Cedré, Bárbara; Valmaseda, Tania; Falero, Gustavo; Pérez, José L; Infante, Juan F; García, Luis G; Solís, Rosa L; Sierra, Gustavo; Talavera, Arturo

    2013-01-01

    A vaccine candidate against cholera was developed in the form of oral tablets to avoid difficulties during application exhibited by current whole cell inactivated cholera vaccines. In this study, enteric-coated tablets were used to improve the protection of the active compound from gastric acidity. Tablets containing heat-killed whole cells of Vibrio cholerae strain C7258 as the active pharmaceutical compound was enteric-coated with the polymer Kollicoat(®) MAE-100P, which protected them efficiently from acidity when a disintegration test was carried out. Enzyme-linked immunosorbent assay (ELISA) anti-lipopolysaccharide (LPS) inhibition test and Western blot assay revealed the presence of V. cholerae antigens as LPS, mannose-sensitive haemagglutinin (MSHA) and outer membrane protein U (Omp U) in enteric-coated tablets. Immunogenicity studies (ELISA and vibriocidal test) carried out by intraduodenal administration in rabbits showed that the coating process of tablets did not affect the immunogenicity of V. cholerae-inactivated cells. In addition, no differences were observed in the immune response elicited by enteric-coated or uncoated tablets, particularly because the animal model and immunization route used did not allow discriminating between acid resistances of both tablets formulations in vivo. Clinical studies with volunteers will be required to elucidate this aspect, but the results suggest the possibility of using enteric-coated tablets as a final pharmaceutical product for a cholera vaccine. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Co-administration of live measles and yellow fever vaccines and inactivated pentavalent vaccines is associated with increased mortality compared with measles and yellow fever vaccines only. An observational study from Guinea-Bissau

    DEFF Research Database (Denmark)

    Fisker, Ane Bærent; Ravn, Henrik Bylling; Rodrigues, Amabelia

    2014-01-01

    Studies from low-income countries indicate that co-administration of inactivated diphtheria-tetanus-pertussis (DTP) vaccine and live attenuated measles vaccine (MV) is associated with increased mortality compared with receiving MV only. Pentavalent (DTP-H. Influenza type B-Hepatitis B) vaccine...

  15. Assessing Inactivated Polio Vaccine Introduction and Utilization in Kano State, Nigeria, April-November 2015.

    Science.gov (United States)

    Osadebe, Lynda U; MacNeil, Adam; Elmousaad, Hashim; Davis, Lora; Idris, Jibrin M; Haladu, Suleiman A; Adeoye, Olorunsogo B; Nguku, Patrick; Aliu-Mamudu, Uneratu; Hassan, Elizabeth; Vertefeuille, John; Bloland, Peter

    2017-07-01

    Kano State, Nigeria, introduced inactivated polio vaccine (IPV) into its routine immunization (RI) schedule in March 2015 and was the pilot site for an RI data module for the National Health Management Information System (NHMIS). We determined factors impacting IPV introduction and the value of the RI module on monitoring new vaccine introduction. Two assessment approaches were used: (1) analysis of IPV vaccinations reported in NHMIS, and (2) survey of 20 local government areas (LGAs) and 60 associated health facilities (HF). By April 2015, 66% of LGAs had at least 20% of HFs administering IPV, by June all LGAs had HFs administering IPV and by July, 91% of the HFs in Kano reported administering IPV. Among surveyed staff, most rated training and implementation as successful. Among HFs, 97% had updated RI reporting tools, although only 50% had updated microplans. Challenges among HFs included: IPV shortages (20%), hesitancy to administer 2 injectable vaccines (28%), lack of knowledge on multi-dose vial policy (30%) and age of IPV administration (8%). The introduction of IPV was largely successful in Kano and the RI module was effective in monitoring progress, although certain gaps were noted, which should be used to inform plans for future vaccine introductions. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

  16. 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

  17. Newcastle disease virus-based H5 influenza vaccine protects chickens from lethal challenge with a highly pathogenic H5N2 avian influenza virus.

    Science.gov (United States)

    Ma, Jingjiao; Lee, Jinhwa; Liu, Haixia; Mena, Ignacio; Davis, A Sally; Sunwoo, Sun Young; Lang, Yuekun; Duff, Michael; Morozov, Igor; Li, Yuhao; Yang, Jianmei; García-Sastre, Adolfo; Richt, Juergen A; Ma, Wenjun

    2017-01-01

    Since December 2014, Eurasian-origin, highly pathogenic avian influenza H5 viruses including H5N1, H5N2, and H5N8 subtypes (called H5N x viruses), which belong to the H5 clade 2.3.4.4, have been detected in U.S. wild birds. Subsequently, highly pathogenic H5N2 and H5N8 viruses have caused outbreaks in U.S. domestic poultry. Vaccination is one of the most effective ways to control influenza outbreaks and protect animal and public health. Newcastle disease virus (NDV)-based influenza vaccines have been demonstrated to be efficacious and safe in poultry. Herein, we developed an NDV-based H5 vaccine (NDV-H5) that expresses a codon-optimized ectodomain of the hemagglutinin from the A/chicken/Iowa/04-20/2015 (H5N2) virus and evaluated its efficacy in chickens. Results showed that both live and inactivated NDV-H5 vaccines induced hemagglutinin inhibition antibody titers against the H5N2 virus in immunized chickens after prime and booster, and both NDV-H5 vaccines completely protected chickens from lethal challenge with the highly pathogenic H5N2 A/turkey/Minnesota/9845-4/2015 virus. No clinical signs and only minimal virus shedding was observed in both vaccinated groups. In contrast, all mock-vaccinated, H5N2-infected chickens shed virus and died within 5 days post challenge. Furthermore, one dose of the live NDV-H5 vaccine also provided protection of 90% chickens immunized by coarse spraying; after exposure to H5N2 challenge, sera from vaccinated surviving chickens neutralized both highly pathogenic H5N1 and H5N8 viruses. Taken together, our results suggest that the NDV-based H5 vaccine is able to protect chickens against intercontinental highly pathogenic H5N x viruses and can be used by mass application to protect the poultry industry.

  18. Green propolis phenolic compounds act as vaccine adjuvants, improving humoral and cellular responses in mice inoculated with inactivated vaccines

    Directory of Open Access Journals (Sweden)

    Geferson Fischer

    2010-11-01

    Full Text Available Adjuvants play an important role in vaccine formulations by increasing their immunogenicity. In this study, the phenolic compound-rich J fraction (JFR of a Brazilian green propolis methanolic extract stimulated cellular and humoral immune responses when co-administered with an inactivated vaccine against swine herpesvirus type 1 (SuHV-1. When compared to control vaccines that used aluminium hydroxide as an adjuvant, the use of 10 mg/dose of JFR significantly increased (p < 0.05 neutralizing antibody titres against SuHV-1, as well as the percentage of protected animals following SuHV-1 challenge (p < 0.01. Furthermore, addition of phenolic compounds potentiated the performance of the control vaccine, leading to increased cellular and humoral immune responses and enhanced protection of animals after SuHV-1 challenge (p < 0.05. Prenylated compounds such as Artepillin C that are found in large quantities in JFR are likely to be the substances that are responsible for the adjuvant activity.

  19. Retinoic acid facilitates inactivated transmissible gastroenteritis virus induction of CD8+ T-cell migration to the porcine gut

    Science.gov (United States)

    Chen, Xiaojuan; Tu, Chongzhi; Qin, Tao; Zhu, Liqi; Yin, Yinyan; Yang, Qian

    2016-01-01

    The digestive tract is the entry site for transmissible gastroenteritis virus (TGEV). TGEV transmission can be prevented if local immunity is established with increased lymphocytes. The current parenteral mode of vaccination stimulates systemic immunity well, but it does not induce sufficient mucosal immunity. Retinoic acid (RA) plays an important role in the induction of cells that imprint gut-homing molecules. We examined whether RA assist parenteral vaccination of pigs could improve mucosal immunity. We demonstrated that elevated numbers of gut-homing CD8+ T cells (which express α4β7 and CCR9 molecules) were presented in porcine inguinal lymph nodes and were recruited to the small intestine by RA. Intestinal mucosal immunity (IgA titre) and systemic immunity (serum IgG titre) were enhanced by RA. Therefore, we hypothesized that RA could induce DCs to form an immature mucosal phenotype and could recruit them to the small intestinal submucosa. Porcine T-cells expressed β7 integrin and CCR9 receptors and migrated to CCL25 by a mechanism that was dependent of activation by RA-pretreated DCs, rather than direct activation by RA. Together, our results provide powerful evidence that RA can assist whole inactivated TGEV (WI-TGEV) via subcutaneous (s.c.) immunization to generate intestinal immunity, and offer new vaccination strategies against TGEV. PMID:27080036

  20. Retinoic acid facilitates inactivated transmissible gastroenteritis virus induction of CD8(+) T-cell migration to the porcine gut.

    Science.gov (United States)

    Chen, Xiaojuan; Tu, Chongzhi; Qin, Tao; Zhu, Liqi; Yin, Yinyan; Yang, Qian

    2016-04-15

    The digestive tract is the entry site for transmissible gastroenteritis virus (TGEV). TGEV transmission can be prevented if local immunity is established with increased lymphocytes. The current parenteral mode of vaccination stimulates systemic immunity well, but it does not induce sufficient mucosal immunity. Retinoic acid (RA) plays an important role in the induction of cells that imprint gut-homing molecules. We examined whether RA assist parenteral vaccination of pigs could improve mucosal immunity. We demonstrated that elevated numbers of gut-homing CD8(+) T cells (which express α4β7 and CCR9 molecules) were presented in porcine inguinal lymph nodes and were recruited to the small intestine by RA. Intestinal mucosal immunity (IgA titre) and systemic immunity (serum IgG titre) were enhanced by RA. Therefore, we hypothesized that RA could induce DCs to form an immature mucosal phenotype and could recruit them to the small intestinal submucosa. Porcine T-cells expressed β7 integrin and CCR9 receptors and migrated to CCL25 by a mechanism that was dependent of activation by RA-pretreated DCs, rather than direct activation by RA. Together, our results provide powerful evidence that RA can assist whole inactivated TGEV (WI-TGEV) via subcutaneous (s.c.) immunization to generate intestinal immunity, and offer new vaccination strategies against TGEV.

  1. Pathogen inactivation of Dengue virus in red blood cells using amustaline and glutathione.

    Science.gov (United States)

    Aubry, Maite; Laughhunn, Andrew; Santa Maria, Felicia; Lanteri, Marion C; Stassinopoulos, Adonis; Musso, Didier

    2017-12-01

    Dengue virus (DENV) is an arbovirus primarily transmitted through mosquito bite; however, DENV transfusion-transmitted infections (TTIs) have been reported and asymptomatic DENV RNA-positive blood donors have been identified in endemic countries. DENV is considered a high-risk pathogen for blood safety. One of the mitigation strategies to prevent arbovirus TTIs is pathogen inactivation. In this study we demonstrate that the amustaline and glutathione (S-303/GSH) treatment previously found effective against Zika virus in red blood cells (RBCs) is also effective in inactivating DENV. Red blood cells were spiked with high levels of DENV. Viral RNA loads and infectious titers were measured in the untreated control and before and after pathogen inactivation treatment of RBC samples. DENV infectivity was also assessed over five successive cell culture passages to detect any potential residual replicative virus. The mean ± SD DENV titer in RBCs before inactivation was 6.61 ± 0.19 log 50% tissue culture infectious dose (TCID 50 )/mL and the mean viral RNA load was 8.42 log genome equivalents/mL. No replicative DENV was detected either immediately after completion of treatment using S-303/GSH or after cell culture passages. Treatment using S-303/GSH inactivated high levels of DENV in RBCs to the limit of detection. In combination with previous studies showing the effective inactivation of DENV in plasma and platelets using the licensed amotosalen/UVA system, this study demonstrates that high levels of DENV can be inactivated in all blood components. © 2017 The Authors Transfusion published by Wiley Periodicals, Inc. on behalf of AABB.

  2. Review of 10 years of marketing experience with Chinese domestic inactivated hepatitis A vaccine Healive®

    Science.gov (United States)

    Wu, Jun-Yu; Liu, Yan; Chen, Jiang-Ting; Xia, Ming; Zhang, Xiao-Mei

    2012-01-01

    In 2002, the first Chinese domestic preservative-free inactivated hepatitis A vaccine, Healive®, was introduced in China. It is highly immunogenic, and provides lasting protection in healthy individuals and generates protective levels of antibodies in other at-risk individuals. Over 10 years since its first licensure, postmarketing surveillance data have confirmed the outstanding safety profile of the vaccine. Comparative clinical trials indicated that Healive® induce equal or similar immunogenicity with other currently available inactivated hepatitis A vaccines and are interchangeable for the course of HAV immunization in Chinese children. The vaccine is effective in curbing outbreaks of hepatitis A due to rapid seroconversion and the long incubation period of the disease. Additional issues surrounding the use of the vaccine are also reviewed. PMID:23032165

  3. Induction of uterine cancer with inactivated herpes simplex virus, types 1 and 2

    International Nuclear Information System (INIS)

    Wentz, W.B.; Reagan, J.W.; Heggie, A.D.; Fu, Y.S.; Anthony, D.D.

    1981-01-01

    A series of studies were performed to evaluate the oncogenic potential of inactivated herpes simplex viruses types 1 (HSV-1) and 2 (HSV-2) in the mouse cervix. HSV-1 or HSV-2 prepared in HEp-2 cell cultures and inactivated by exposure to formalin or ultraviolet light was applied to the mouse cervix for periods ranging from 20 to 90 weeks. Control mice were exposed for the same period to control fluids. Vaginal cytologic preparations from all animals were examined weekly to detect epithelial abnormalities. Animals were sacrificed and histopathological studies were carried out when cellular changes seen on vaginal smears resembled those indicative of premalignant or malignant changes as previously established in a similar model system using coal tar hydrocarbons. Other animals were exposed for periods up to 90 weeks, or until there was cellular evidence of invasive cancer. Cytologic and histologic materials were coded and evaluated without knowledge of whether they were from virus-exposed or control animals. Premalignant and malignant cervical lesions similar to those that occur in women were encountered in 78 to 90% of the virus-exposed animals. All controls were normal. Invasive cancer was detected in 24 to 60% of the animals and dysplasia was found in 18 to 66%. The yield of invasive cancer was twice as great after exposure to ultraviolet-inactivated HSV-2 as compared with formalin-inactivated virus. Various histologic grades of carcinoma of the cervix and endometrium were found. No primary lesions were found in the vagina or ovaries

  4. 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

  5. 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

  6. Comparative study of methods for inactivation of vaccines on development process of veterinary “Ghost” vaccine

    International Nuclear Information System (INIS)

    Pencheva, Daniela; Genova-Kalou, Petia; Bryaskova, Rayna

    2016-01-01

    Experimental and laboratory tests were carried out in order to identify the advantages of “ghost” antigens obtained by treatment of the bacterial cell with silver nanoparticles in comparison to the inactivated antigens obtained by classical methods as heating or treatment with formalin. The Minimal Bactericidal Concentrations (MBC) of the hybrid material containing silver nanoparticles (PVA/AgNps), used for inactivation of the tested E. coli strains were determined and they were categorized as susceptible to the action of silver nanoparticles. The changes in the structure of the bacterial cells obtained after the treatment with the hybrid material containing silver nanoparticles or with formaldehyde, respectively, were established by TEM (Transmission electron microscopy) analysis. The advantages of the “ghost” vaccines are expressed in undamaged cell wall and better immunogenicity, thus resulting in faster formation of specific titer after immunization of experimental animals. Key words: E. coli O149, E. coli O157H7, “ghost” vaccine, silver nanoparticles, TEM

  7. Immunogenicity, safety, and interchangeability of two inactivated hepatitis A vaccines in Chilean children.

    Science.gov (United States)

    Abarca, Katia; Ibánez, Isabel; Perret, Cecilia; Vial, Pablo; Zinsou, Jean-Antoine

    2008-05-01

    To compare the immunogenicity, safety, and interchangeability of two pediatric hepatitis A vaccines, Avaxim 80U-Pediatric and Havrix 720, in Chilean children. In this randomized trial, 332 hepatitis A virus (HAV) seronegative children from 1 to 15 years of age received two doses of Avaxim, two doses of Havrix, or Havrix followed by Avaxim, 6 months apart. Anti-HAV antibody titers were measured before and 14 days after the first dose of vaccine, and before and 28 days after the second dose of vaccine. Immediate reactions were monitored; reactogenicity was evaluated from parental reports. Seroconversion rates after the first vaccination were 99.4% and 100% for Avaxim and Havrix, respectively. Anti-HAV geometric mean concentrations (GMCs) were 138 mIU/ml for Havrix (95% confidence interval (CI): 120; 159) and 311 mIU/ml for Avaxim (95% CI: 274; 353). GMCs increased to 4008 mIU/ml after two doses of Havrix, 8537 mIU/ml following two doses of Avaxim, and 7144 mIU/ml in children who received Havrix with Avaxim as the second dose. Following the first injection, 36% of subjects given Avaxim and 44% given Havrix reported local reactions; 38% of subjects in the Avaxim group and 40% in the Havrix group reported systemic reactions related to vaccination. Solicited reactions were less frequent after the second dose of Avaxim or Havrix, occurring in 27% to 37% of subjects. No significant difference in seroconversion rates was seen 14 days after a single dose of vaccine. A two-dose schedule with either vaccine or with Havrix/Avaxim provided a strong booster response. Both vaccines were well tolerated and can be recommended for routine vaccination of Chilean children. Avaxim 80 may be used to complete a vaccine schedule begun with Havrix 720.

  8. Coated microneedle arrays for transcutaneous delivery of live virus vaccines

    Science.gov (United States)

    Vrdoljak, Anto; McGrath, Marie G.; Carey, John B.; Draper, Simon J.; Hill, Adrian V.S.; O’Mahony, Conor; Crean, Abina M.; Moore, Anne C.

    2016-01-01

    Vaccines are sensitive biologics that require continuous refrigerated storage to maintain their viability. The vast majority of vaccines are also administered using needles and syringes. The need for cold chain storage and the significant logistics surrounding needle-and-syringe vaccination is constraining the success of immunization programs. Recombinant live viral vectors are a promising platform for the development of vaccines against a number of infectious diseases, however these viruses must retain infectivity to be effective. Microneedles offer an effective and painless method for delivery of vaccines directly into skin that in the future could provide solutions to current vaccination issues. Here we investigated methods of coating live recombinant adenovirus and modified vaccinia virus Ankara (MVA) vectors onto solid microneedle arrays. An effective spray-coating method, using conventional pharmaceutical processes, was developed, in tandem with suitable sugar-based formulations, which produces arrays with a unique coating of viable virus in a dry form around the shaft of each microneedle on the array. Administration of live virus-coated microneedle arrays successfully resulted in virus delivery, transcutaneous infection and induced an antibody or CD8+ T cell response in mice that was comparable to that obtained by needle-and-syringe intradermal immunization. To our knowledge, this is the first report of successful vaccination with recombinant live viral vectored vaccines coated on microneedle delivery devices. PMID:22245683

  9. Immunity to viruses: learning from successful human vaccines.

    Science.gov (United States)

    Pulendran, Bali; Oh, Jason Z; Nakaya, Helder I; Ravindran, Rajesh; Kazmin, Dmitri A

    2013-09-01

    For more than a century, immunologists and vaccinologists have existed in parallel universes. Immunologists have for long reveled in using 'model antigens', such as chicken egg ovalbumin or nitrophenyl haptens, to study immune responses in model organisms such as mice. Such studies have yielded many seminal insights about the mechanisms of immune regulation, but their relevance to humans has been questioned. In another universe, vaccinologists have relied on human clinical trials to assess vaccine efficacy, but have done little to take advantage of such trials for studying the nature of immune responses to vaccination. The human model provides a nexus between these two universes, and recent studies have begun to use this model to study the molecular profile of innate and adaptive responses to vaccination. Such 'systems vaccinology' studies are beginning to provide mechanistic insights about innate and adaptive immunity in humans. Here, we present an overview of such studies, with particular examples from studies with the yellow fever and the seasonal influenza vaccines. Vaccination with the yellow fever vaccine causes a systemic acute viral infection and thus provides an attractive model to study innate and adaptive responses to a primary viral challenge. Vaccination with the live attenuated influenza vaccine causes a localized acute viral infection in mucosal tissues and induces a recall response, since most vaccinees have had prior exposure to influenza, and thus provides a unique opportunity to study innate and antigen-specific memory responses in mucosal tissues and in the blood. Vaccination with the inactivated influenza vaccine offers a model to study immune responses to an inactivated immunogen. Studies with these and other vaccines are beginning to reunite the estranged fields of immunology and vaccinology, yielding unexpected insights about mechanisms of viral immunity. Vaccines that have been proven to be of immense benefit in saving lives offer us a new

  10. Alkaline stabilization of manure slurry inactivates porcine epidemic diarrhea virus

    Science.gov (United States)

    The porcine epidemic diarrhea virus (PEDv) outbreak in North America has substantially impacted swine production since it causes nearly 100% mortality in infected pre-weaned piglets. The PED virus is transmitted via the fecal oral route and manure may remain a source of reinfection; therefore, prop...

  11. Dual-Emission Fluorescence Resonance Energy Transfer (FRET) Real-Time PCR Differentiates Feline Immunodeficiency Virus Subtypes and Discriminates Infected from Vaccinated Cats▿ §

    OpenAIRE

    Wang, Chengming; Johnson, Calvin M.; Ahluwalia, Sudhir K.; Chowdhury, Erfan; Li, Yihang; Gao, Dongya; Poudel, Anil; Rahman, K. Shamsur; Kaltenboeck, Bernhard

    2010-01-01

    Feline immunodeficiency virus (FIV) is among the most common infectious agents of cats. Five well-characterized FIV subtypes, A, B, C, D, and E, are recognized worldwide. As in HIV diagnosis, serum antibodies against FIV classically serve as an indicator of infection status. After the introduction of an inactivated FIV vaccine, this approach has become problematic, since antibodies generated by vaccination are indistinguishable from antibodies in response to infection. However, PCR detection ...

  12. Effect of passive immunization on immunogenicity and protective efficacy of vaccination against a Mexican low-pathogenic avian H5N2 influenza virus.

    Science.gov (United States)

    Forrest, Heather L; Garcia, Alejandro; Danner, Angela; Seiler, Jon P; Friedman, Kimberly; Webster, Robert G; Jones, Jeremy C

    2013-11-01

    Despite the use of vaccines, low-pathogenic (LP) H5N2 influenza viruses have continued to circulate and evolve in chickens in Mexico since 1993, giving rise to multiple genetic variants. Antigenic drift is partially responsible for the failure to control H5N2 influenza by vaccination; the contribution of maternal antibodies to this problem has received less attention. We investigated the effect of different antisera on the efficacy of vaccination and whether booster doses of vaccine can impact immune suppression. While single doses of inactivated oil emulsion vaccine to currently circulating H5N2 influenza viruses provide partial protection from homologous challenge, chickens that receive high-titer homologous antisera intraperitoneally before vaccination showed effects ranging from added protection to immunosuppression. Post-infection antisera were less immunosuppressive than antisera obtained from field-vaccinated chickens. Homologous, post-infection chicken antisera provided initial protection from virus challenge, but reduced the induction of detectable antibody responses. Homologous antisera from field-vaccinated chickens were markedly immunosuppressive, annulling the efficacy of the vaccine and leaving the chickens as susceptible to infection as non-vaccinated birds. Booster doses of vaccine reduced the immunosuppressive effects of the administered sera. Vaccine efficacy against LP H5N2 in Mexico can be severely reduced by maternal antibodies. Source-dependent antisera effects offer the possibility of further elucidation of the immunosuppressive components involved. © 2013 John Wiley & Sons Ltd.

  13. 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.

    Science.gov (United States)

    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.

  14. Newcastle disease virus outbreaks: vaccine mismatch or inadequate application?

    Science.gov (United States)

    Dortmans, Jos C F M; Peeters, Ben P H; Koch, Guus

    2012-11-09

    Newcastle disease (ND) is one of the most important diseases of poultry, and may cause devastating losses in the poultry industry worldwide. Its causative agent is Newcastle disease virus (NDV), also known as avian paramyxovirus type 1. Many countries maintain a stringent vaccination policy against ND, but there are indications that ND outbreaks can still occur despite intensive vaccination. It has been argued that this may be due to antigenic divergence between the vaccine strains and circulating field strains. Here we present the complete genome sequence of a highly virulent genotype VII virus (NL/93) obtained from vaccinated poultry during an outbreak of ND in the Netherlands in 1992-1993. Using this strain, we investigated whether the identified genetic evolution of NDV is accompanied by antigenic evolution. In this study we show that a live vaccine that is antigenically adapted to match the genotype VII NL/93 outbreak strain does not provide increased protection compared to a classic genotype II live vaccine. When challenged with the NL/93 strain, chickens vaccinated with a classic vaccine were completely protected against clinical disease and mortality and virus shedding was significantly reduced, even with a supposedly suboptimal vaccine dose. These results suggest that it is not antigenic variation but rather poor flock immunity due to inadequate vaccination practices that may be responsible for outbreaks and spreading of virulent NDV field strains. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. Foot and mouth disease virus transmission among vaccinated pigs after exposure to virus shedding pigs

    NARCIS (Netherlands)

    Orsel, K.; Jong, de M.C.M.; Bouma, A.; Stegeman, J.A.; Dekker, A.

    2007-01-01

    The aim of this study was to design a transmission experiment that enabled quantification of the effectiveness of vaccination against foot and mouth disease (FMD) virus in groups of pigs. Previous experiments showed that intradermal injection of pigs with FMD virus 14 days after vaccination was not

  16. Systematic review and meta-analysis of the effectiveness of commercially available vaccines against bovine herpesvirus, bovine viral diarrhea virus, bovine respiratory syncytial virus, and parainfluenza type 3 virus for mitigation of bovine respiratory disease complex in cattle.

    Science.gov (United States)

    Theurer, Miles E; Larson, Robert L; White, Brad J

    2015-01-01

    To evaluate and analyze data from controlled studies on the effectiveness of vaccinating cattle with commercially available viral antigen vaccines for mitigation of the effects of bovine respiratory disease complex (BRDC). Systematic review and meta-analysis. 31 studies comprising 88 trials. Studies that reported the effectiveness of commercially available bovine herpesvirus-1 (BHV-1), bovine viral diarrhea virus (BVDV), bovine respiratory syncytial virus (BRSV), and parainfluenza type 3 virus (PI3) vaccines for protection of cattle against BRDC or its components were included in the analysis. Studies or trials were categorized as natural exposure or experimental challenge and were further divided by the viral antigen evaluated and vaccine type (modified-live virus [MLV] or inactivated vaccine). Meta-analysis was performed; summary Mantel-Haenszel risk ratios were determined, and Forest plots were generated. In natural exposure trials, beef calves vaccinated with various antigen combinations had a significantly lower BRDC morbidity risk than did nonvaccinated control calves. In trials evaluating BHV-1 and MLV BVDV vaccines in experimental challenge models, vaccinated calves had a lower BRDC morbidity risk than did control calves; however, in experimental challenge trials evaluating MLV BRSV and PI3 vaccines, no significant difference in morbidity or mortality risk was found between vaccinated and control calves. Estimating clinical efficacy from results of experimental challenge studies requires caution because these models differ substantially from those involving natural exposure. The literature provides data but does not provide sufficiently strong evidence to guide definitive recommendations for determining which virus components are necessary to include in a vaccination program for prevention or mitigation of BRDC in cattle.

  17. Inactivation of human enteric virus surrogates by high-intensity ultrasound.

    Science.gov (United States)

    Su, Xiaowei; Zivanovic, Svetlana; D'Souza, Doris H

    2010-09-01

    Foodborne viruses, especially human noroviruses, are recognized as leading causes of nonbacterial gastroenteritis worldwide. Development of effective inactivation methods is of great importance to control their spread. In this study, the effect of high-intensity ultrasound (HIUS) on the infectivity of three foodborne virus surrogates was investigated. The three surrogates, murine norovirus (MNV-1), feline calicivirus (FCV-F9), and MS2 bacteriophage, were diluted in phosphate-buffered saline (PBS) or orange juice to a titer of approximately 6 log(10) PFU/mL or approximately 4 log(10) PFU/mL. The ultrasound treatment was performed in duplicate by immersing the HIUS probe in virus-containing solution that was cooled in ice-water and sonicated at 20 kHz for 2, 5, 10, 15, 20, and 30 min with 30 sec on and 30 sec off. The infectivity of the recovered viruses after each ultrasound treatment was evaluated in duplicate using standardized plaque assays and compared to untreated controls. The results show that HIUS effectiveness depended on the virus type, the initial titer of the viruses, and the virus suspension solution. At titers of approximately 4 log(10) PFU/mL in PBS, feline calicivirus (FCV)-F9, MS2, and murine norovirus (MNV)-1 required 5-, 10-, and 30-min treatment, respectively, for complete inactivation. At initial titers of approximately 4 log(10) PFU/mL in orange juice, FCV-F9 required a 15-min treatment for complete inactivation and only a 1.55 log(10) PFU/mL reduction was achieved for MNV-1 in orange juice after 30-min treatment. Thus, inactivation by HIUS in orange juice was much lower than in PBS. Experiments using titers of approximately 6 log(10) PFU/mL showed decreased effects compared to those using titers of approximately 4 log(10) PFU/mL. These results indicate that HIUS alone is not sufficient to inactivate virus in food. Hurdle technologies that combine HIUS with antimicrobials, heat, or pressure should be explored for viral inactivation.

  18. Acceptability of Aujeszky's disease vaccines.

    Science.gov (United States)

    Kimman, T G

    1992-01-01

    Vaccines against Aujeszky's disease are not only used to prevent the clinical consequences of a field infection, but also to support eradication of the virus. The current Aujeszky's disease vaccines (ADV) protect against severe clinical signs of disease and they reduce but usually do not prevent virus multiplication and excretion or the establishment of latency after infection. Vaccines also limit virus multiplication after reactivation. The efficacy of vaccination is reduced by passively acquired maternal antibodies. The mechanisms that afford immunity to the virus are only poorly understood. No simple parameters for immunity are therefore available. The European Pharmacopoeia formulates requirements for inactivated and live ADV vaccines for parenteral use. The vaccines must be safe; they must not induce local or systemic reactions; they must not be transmitted to unvaccinated pigs; they must not be transmitted by semen and across the placenta; the attenuation must be irreversible (live vaccines); the inactivation must be complete (inactivated vaccines); they must prevent mortality and limit growth retardation after challenge infection; the vaccine must not contain contaminating micro-organisms and viruses. No requirements have been formulated with regard to reduction of excretion of challenge virus after experimental infection, efficacy in pigs with maternal antibodies, reproducibility of efficacy studies, reduction of virus transmission under field conditions, the presence of a serological marker, safety for other species, and safety and efficacy of intranasally administered vaccines. Future developments should be directed to the development and evaluation of ADV vaccines that are able to limit transmission of the virus.

  19. Gene Constellation of Influenza A Virus Reassortants with High Growth Phenotype Prepared as Seed Candidates for Vaccine Production

    Science.gov (United States)

    Fulvini, Andrew A.; Ramanunninair, Manojkumar; Le, Jianhua; Pokorny, Barbara A.; Arroyo, Jennifer Minieri; Silverman, Jeanmarie; Devis, Rene; Bucher, Doris

    2011-01-01

    Background Influenza A virus vaccines undergo yearly reformulations due to the antigenic variability of the virus caused by antigenic drift and shift. It is critical to the vaccine manufacturing process to obtain influenza A seed virus that is antigenically identical to circulating wild type (wt) virus and grows to high titers in embryonated chicken eggs. Inactivated influenza A seasonal vaccines are generated by classical reassortment. The classical method takes advantage of the ability of the influenza virus to reassort based on the segmented nature of its genome. In ovo co-inoculation of a high growth or yield (hy) donor virus and a low yield wt virus with antibody selection against the donor surface antigens results in progeny viruses that grow to high titers in ovo with wt origin hemagglutinin (HA) and neuraminidase (NA) glycoproteins. In this report we determined the parental origin of the remaining six genes encoding the internal proteins that contribute to the hy phenotype in ovo. Methodology The genetic analysis was conducted using reverse transcription-polymerase chain reaction (RT-PCR) and restriction fragment length polymorphism (RFLP). The characterization was conducted to determine the parental origin of the gene segments (hy donor virus or wt virus), gene segment ratios and constellations. Fold increase in growth of reassortant viruses compared to respective parent wt viruses was determined by hemagglutination assay titers. Significance In this study fifty-seven influenza A vaccine candidate reassortants were analyzed for the presence or absence of correlations between specific gene segment ratios, gene constellations and hy reassortant phenotype. We found two gene ratios, 6∶2 and 5∶3, to be the most prevalent among the hy reassortants analyzed, although other gene ratios also conferred hy in certain reassortants. PMID:21695145

  20. Antibody response of sandhill and whooping cranes to an eastern equine encephalitis virus vaccine

    Science.gov (United States)

    Clark, G.G.; Dein, F.J.; Crabbs, C.L.; Carpenter, J.W.; Watts, D.M.

    1987-01-01

    As a possible strategy to protect whooping cranes (Grus americana) from fatal eastern equine encephalitis (EEE) viral infection, studies were conducted to determine the immune response of this species and sandhill cranes (Grus canadensis) to a formalin-inactivated EEE viral vaccine. Viral-specific neutralizing antibody was elicited in both species after intramuscular (IM) vaccination. Subcutaneous and intravenous routes of vaccination failed to elicit detectable antibody in sandhill cranes. Among the IM vaccinated cranes, the immune response was characterized by nondetectable or low antibody titers that waned rapidly following primary exposure to the vaccine. However, one or more booster doses consistently elicited detectable antibody and/or increased antibody titers in the whooping cranes. In contrast, cranes with pre-existing EEE viral antibody, apparently induced by natural infection, exhibited a rapid increase and sustained high-antibody titers. Even though EEE virus vaccine induced neutralizing antibody and produced no adverse side effects, further studies will be required to determine the protective efficacy of the antibody.

  1. 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

  2. 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...

  3. Distinction between infections with European and American/vaccine type PRRS virus after vaccination with a modified-live PRRS virus vaccine

    DEFF Research Database (Denmark)

    Bøtner, Anette; Strandbygaard, Bertel; Sørensen, K. J.

    2000-01-01

    In July 1996 a modified live Porcine reproductive and respiratory syndrome (PRRS) vaccine, based on an American (US) strain of the PRRS virus (PRRSV), was licensed in Denmark. The vaccine was licensed for use in 3-18 week old pigs, exclusively. Starting during the middle of October 1996, several...... herds who had recently begun vaccination, experienced acute PRRS-like symptoms including an increasing number of abortions and stillborn piglets and an increasing mortality in the nursing period. During the period from October 1996 until May 1997, the PRRS virus (PRRSV), identified as the vaccine....../US type of PRRSV, was isolated from fetuses, dead piglets, pleural fluids and/or lung tissues from 114 of such herds. These findings indicated the spread of the vaccine virus to non-vaccinated sows followed by transplacental infection of fetuses. Also, a number of not previously PRRSV infected and non-vaccinated...

  4. Inactivation of viruses and bacteria in sewage sludge by gamma radiation

    International Nuclear Information System (INIS)

    Stettmund von Brodorotti, H.; Mahnel, H.

    1980-01-01

    The kinetics of inactivation and the resistance to gamma radiation of microorganisms usually to be found in raw sludge were examined with five viruses, three bacteria and a fungus serving as prototypes in comparative studies. All these infectious agents could reliably be inactivated by gamma rays in raw sewage sludge but they were dearly more resistant to gamma rays compared to irradiation in a liquid suspension. The reduction of the virus content required a much higher radiation dose compared to bacteria and the fungus used, excluding Streptococcus faecalis which was exceptionally resistant. Considering the content of pathogenic viruses and other agents in raw sewage sludge, the required radiation dose necessary to comply with average to strict demands for the hygienisation of sewage sludge is discussed. The radiation dose of 500 to 1,000 krad seems therefore to be sufficient. (orig.) [de

  5. 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.

  6. Rift Valley Fever Vaccine Virus Clone 13 Is Able to Cross the Ovine Placental Barrier Associated with Foetal Infections, Malformations, and Stillbirths

    Science.gov (United States)

    Makoschey, Birgit; van Kilsdonk, Emma; Hubers, Willem R.; Vrijenhoek, Mieke P.; Smit, Marianne; Wichgers Schreur, Paul J.; Kortekaas, Jeroen; Moulin, Véronique

    2016-01-01

    Rift Valley fever virus (RVFV) is a mosquito-borne pathogen that affects domesticated ruminants and occasionally humans. Classical RVF vaccines are based on formalin-inactivated virus or the live-attenuated Smithburn strain. The inactivated vaccine is highly safe but requires multiple administrations and yearly re-vaccinations. Although the Smithburn vaccine provides solid protection after a single vaccination, this vaccine is not safe for pregnant animals. An alternative live-attenuated vaccine, named Clone 13, carries a large natural deletion in the NSs gene which encodes the major virulence factor of the virus. The Clone 13 vaccine was previously shown to be safe for young lambs and calves. Moreover, a study in pregnant ewes suggested that the vaccine could also be applied safely during gestation. To anticipate on a possible future incursion of RVFV in Europe, we have evaluated the safety of Clone 13 for young lambs and pregnant ewes. In line with the guidelines from the World Organisation for Animal health (Office International des Epizooties, OIE) and regulations of the European Pharmacopeia (EP), these studies were performed with an overdose. Our studies with lambs showed that Clone 13 dissemination within vaccinated animals is very limited. Moreover, the Clone 13 vaccine virus was not shed nor spread to in-contact sentinels and did not revert to virulence upon animal-to-animal passage. Importantly, a large experiment with pregnant ewes demonstrated that the Clone 13 virus is able to spread to the fetus, resulting in malformations and stillbirths. Altogether, our results suggest that Clone 13 can be applied safely in lambs, but that caution should be taken when Clone 13 is used in pregnant animals, particularly during the first trimester of gestation. PMID:27031621

  7. 9 CFR 113.300 - General requirements for live virus vaccines.

    Science.gov (United States)

    2010-01-01

    ... vaccines. 113.300 Section 113.300 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... REQUIREMENTS Live Virus Vaccines § 113.300 General requirements for live virus vaccines. When prescribed in an applicable Standard Requirement or in the filed Outline of Production, a live virus vaccine shall meet the...

  8. 9 CFR 113.200 - General requirements for killed virus vaccines.

    Science.gov (United States)

    2010-01-01

    ... vaccines. 113.200 Section 113.200 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... REQUIREMENTS Killed Virus Vaccines § 113.200 General requirements for killed virus vaccines. When prescribed in an applicable Standard Requirement or in the filed Outline of Production, a killed virus vaccine...

  9. Fractional-Dose Inactivated Poliovirus Vaccine Campaign - Sindh Province, Pakistan, 2016.

    Science.gov (United States)

    Pervaiz, Aslam; Mbaeyi, Chukwuma; Baig, Mirza Amir; Burman, Ashley; Ahmed, Jamal A; Akter, Sharifa; Jatoi, Fayaz A; Mahamud, Abdirahman; Asghar, Rana Jawad; Azam, Naila; Shah, Muhammad Nadeem; Laghari, Mumtaz Ali; Soomro, Kamaluddin; Wadood, Mufti Zubair; Ehrhardt, Derek; Safdar, Rana M; Farag, Noha

    2017-12-01

    Following the declaration of eradication of wild poliovirus (WPV) type 2 in September 2015, trivalent oral poliovirus vaccine (tOPV) was withdrawn globally to reduce the risk for type 2 vaccine-derived poliovirus (VDPV2) transmission; all countries implemented a synchronized switch to bivalent OPV (type 1 and 3) in April 2016 (1,2). Any isolation of VDPV2 after the switch is to be treated as a potential public health emergency and might indicate the need for supplementary immunization activities (3,4). On August 9, 2016, VDPV2 was isolated from a sewage sample taken from an environmental surveillance site in Hyderabad, Sindh province, Pakistan. Possible vaccination activities in response to VDPV2 isolation include the use of injectable inactivated polio vaccine (IPV), which poses no risk for vaccine-derived poliovirus transmission. Fractional-dose, intradermal IPV (fIPV), one fifth of the standard intramuscular dose, has been developed to more efficiently manage limited IPV supplies. fIPV has been shown in some studies to be noninferior to full-dose IPV (5,6) and was used successfully in response to a similar detection of a single VDPV2 isolate from sewage in India (7). Injectable fIPV was used for response activities in Hyderabad and three neighboring districts. This report describes the findings of an assessment of preparatory activities and subsequent implementation of the fIPV campaign. Despite achieving high coverage (>80%), several operational challenges were noted. The lessons learned from this campaign could help to guide the planning and implementation of future fIPV vaccination activities.

  10. Awareness and Uptake of Human Papilloma Virus Vaccination and ...

    African Journals Online (AJOL)

    Background: Cervical cancer is the second leading malignancy affecting women worldwide. Human papilloma virus (HPV) vaccination protects against developing cervical cancer. The study was designed to determine the awareness and uptake of HPV vaccination and cervical screening among female undergraduates in ...

  11. Deep insight into white spot syndrome virus vaccines: A review

    Directory of Open Access Journals (Sweden)

    MA Badhul Haq

    2012-02-01

    Full Text Available White spot syndrome virus (WSSV, the causative virus of the disease, is found in most shrimp farming areas of the world, where it causes large economic losses to the shrimp farming industry. The potentially fatal virus has been found to be a threat not only to all shrimp species, but also to other marine and freshwater crustaceans, such as crab and crayfish. To date, no effective prophylactic treatment measures are available for viral infections in shrimp and other crustaceans. Due to current aquaculture practices and the broad host range of WSSV, intervention strategies including vaccination against this virus would be pivotal to save and protect shrimp farming. Several achievements have been attained in the search of novel vaccines for WSSV. DNA vaccination, recombinant vaccines, oral vaccination techniques and gene therapy are some of the thrust areas of focus for scientists and researchers. This review article highlights the recent trends in the development of WSSV vaccines either as DNA vaccines or recombinant vaccines and their functioning strategies as suggested by the researchers worldwide.

  12. Human Papilloma Virus Vaccine: Determinants of Acceptability by ...

    African Journals Online (AJOL)

    Vaccination of adolescent females against Human Papilloma Virus (HPV), the causative agent for cervical cancer has recently become available. As minors, parental acceptance of the vaccines for adolescent daughters requires exploration. This was a cross-sectional survey of 201 mothers attending the gynaecology clinic ...

  13. Enveloped virus-like particles as vaccines against pathogenic arboviruses

    NARCIS (Netherlands)

    Pijlman, G.P.

    2015-01-01

    Arthropod-borne arboviruses form a continuous threat to human and animal health, but few arboviral vaccines are currently available. Advances in expression technology for complex, enveloped virus-like particles (eVLPs) create new opportunities to develop potent vaccines against pathogenic

  14. Human Papilloma Virus vaccination: knowledge, attitude and uptake ...

    African Journals Online (AJOL)

    Background: Human papilloma virus (HPV) infection is implicated in the cause of cervical cancer which is the second most common cancer in women worldwide. HPV vaccination is a primary prevention toolagainst HPV infection, thus the need to assess the knowledge, attitude and uptake of HPV vaccination among female ...

  15. Chitosan Nanoparticle Encapsulated Hemagglutinin-Split Influenza Virus Mucosal Vaccine

    OpenAIRE

    Sawaengsak, Chompoonuch; Mori, Yasuko; Yamanishi, Koichi; Mitrevej, Ampol; Sinchaipanid, Nuttanan

    2013-01-01

    Subunit/split influenza vaccines are less reactogenic compared with the whole virus vaccines. However, their immunogenicity is relatively low and thus required proper adjuvant and/or delivery vehicle for immunogenicity enhancement. Influenza vaccines administered intramuscularly induce minimum, if any, mucosal immunity at the respiratory mucosa which is the prime site of the infection. In this study, chitosan (CS) nanoparticles were prepared by ionic cross-linking of the CS with sodium tripol...

  16. Cold-Adapted Viral Attenuation (CAVA): Highly Temperature Sensitive Polioviruses as Novel Vaccine Strains for a Next Generation Inactivated Poliovirus Vaccine

    Science.gov (United States)

    Sanders, Barbara P.; de los Rios Oakes, Isabel; van Hoek, Vladimir; Bockstal, Viki; Kamphuis, Tobias; Uil, Taco G.; Song, Yutong; Cooper, Gillian; Crawt, Laura E.; Martín, Javier; Zahn, Roland; Lewis, John; Wimmer, Eckard; Custers, Jerome H. H. V.; Schuitemaker, Hanneke; Cello, Jeronimo; Edo-Matas, Diana

    2016-01-01

    The poliovirus vaccine field is moving towards novel vaccination strategies. Withdrawal of the Oral Poliovirus Vaccine and implementation of the conventional Inactivated Poliovirus Vaccine (cIPV) is imminent. Moreover, replacement of the virulent poliovirus strains currently used for cIPV with attenuated strains is preferred. We generated Cold-Adapted Viral Attenuation (CAVA) poliovirus strains by serial passage at low temperature and subsequent genetic engineering, which contain the capsid sequences of cIPV strains combined with a set of mutations identified during cold-adaptation. These viruses displayed a highly temperature sensitive phenotype with no signs of productive infection at 37°C as visualized by electron microscopy. Furthermore, decreases in infectious titers, viral RNA, and protein levels were measured during infection at 37°C, suggesting a block in the viral replication cycle at RNA replication, protein translation, or earlier. However, at 30°C, they could be propagated to high titers (9.4–9.9 Log10TCID50/ml) on the PER.C6 cell culture platform. We identified 14 mutations in the IRES and non-structural regions, which in combination induced the temperature sensitive phenotype, also when transferred to the genomes of other wild-type and attenuated polioviruses. The temperature sensitivity translated to complete absence of neurovirulence in CD155 transgenic mice. Attenuation was also confirmed after extended in vitro passage at small scale using conditions (MOI, cell density, temperature) anticipated for vaccine production. The inability of CAVA strains to replicate at 37°C makes reversion to a neurovirulent phenotype in vivo highly unlikely, therefore, these strains can be considered safe for the manufacture of IPV. The CAVA strains were immunogenic in the Wistar rat potency model for cIPV, inducing high neutralizing antibody titers in a dose-dependent manner in response to D-antigen doses used for cIPV. In combination with the highly productive

  17. Effectiveness and safety of immunization with live-attenuated and inactivated vaccines for pediatric liver transplantation recipients.

    Science.gov (United States)

    Kawano, Yoshihiko; Suzuki, Michio; Kawada, Jun-ichi; Kimura, Hiroshi; Kamei, Hideya; Ohnishi, Yasuharu; Ono, Yasuyuki; Uchida, Hiroo; Ogura, Yasuhiro; Ito, Yoshinori

    2015-03-17

    Liver transplantation recipients are at high risk for severe complications due to infections because of being treated with immunosuppressive drugs that affect the immune system. Vaccination for liver transplantation candidates is generally recommended before surgery, but the opportunities for vaccination prior to transplantation in pediatric candidates are often limited by severe disease conditions. The participants in this study comprised 39 pediatric recipients of living donor liver transplantation performed between 2005 and 2013. Criteria for administering live-attenuated (measles, rubella, mumps, and varicella) and inactivated (hepatitis B, pertussis, and Japanese encephalitis) vaccines were as follows: (1) >1 year after transplantation; (2) no use of systemic steroids to treat acute rejection within the last 6 months; (3) serum trough concentration of tacrolimus vaccination for recipients with primary vaccine failure after first vaccination were 100% (8/8), 50% (1/2), 71% (5/7), and 50% (5/10), respectively. While four recipients contracted mumps and eight contracted varicella before immunization, one recipient developed varicella after immunization. No serious systemic adverse events were observed in vaccinated recipients. Seroprotection rates for measles, mumps, and varicella appeared low in children after the first post-transplantation vaccination. Immunizations with four live-attenuated and three inactivated vaccines were safe and effective for pediatric liver transplantation recipients who were not severely immunosuppressed. Copyright © 2015. Published by Elsevier Ltd.

  18. Validation and evaluation of serological correlates of protection for inactivated enterovirus 71 vaccine in children aged 6-35 months.

    Science.gov (United States)

    Jin, Pengfei; Li, Jingxin; Zhang, Xuefeng; Meng, Fangyue; Zhou, Yang; Yao, Xuejun; Gan, Zhengkai; Zhu, Fengcai

    2016-04-02

    A primary goal of this study was to establish the serological mechanistic correlate of protection (mCoP) for an inactivated Enterovirus 71 (EV71) vaccine. We used the Prentice criterion framework and scaled logit model to explore the relationship between the neutralizing antibody (NTAb) and EV71-associated disease, and to build a protection curve for estimating the efficacy of EV71 vaccine. Data of NTAb at day 56 post-vaccination and the occurrence of EV71-associated disease during a 12-month follow-up period were collected from a phase 3 efficacy trial of EV71 vaccine in this study. NTAb at day 56 post-vaccination in participants met the Prentice criterion framework. According to the protection curve, the antibody levels of 14.7, 27.8, 55.7, 129.0 and 459.4 (U/mL) were associated with 50%, 60%, 70%, 80% and 90% clinical protection rate, respectively. Vaccine efficacy predicted by the model was 81.5%, which was very similar to the actual vaccine efficacy of 80.4% (95% CI, 58.2, 90.8) observed in the phase 3 trial. NTAb titers post-vaccination can be validated as mCoP for evaluating the efficacy of an inactivated enterovirus 71 vaccine, with a titers of 14.7 (U/ml) as a surrogate associated with the protection of 50% against EV71-associated disease.

  19. Plasma temperature during methylene blue/light treatment influences virus inactivation capacity and product quality.

    Science.gov (United States)

    Gravemann, U; Handke, W; Sumian, C; Alvarez, I; Reichenberg, S; Müller, T H; Seltsam, A

    2018-02-27

    Photodynamic treatment using methylene blue (MB) and visible light is in routine use for pathogen inactivation of human plasma in different countries. Ambient and product temperature conditions for human plasma during production may vary between production sites. The influence of different temperature conditions on virus inactivation capacity and plasma quality of the THERAFLEX MB-Plasma procedure was investigated in this study. Plasma units equilibrated to 5 ± 2°C, room temperature (22 ± 2°C) or 30 ± 2°C were treated with MB/light and comparatively assessed for the inactivation capacity for three different viruses, concentrations of MB and its photoproducts, activity of various plasma coagulation factors and clotting time. Reduced solubility of the MB pill was observed at 5 ± 2°C. Photocatalytic degradation of MB increased with increasing temperature, and the greatest formation of photoproducts (mainly azure B) occurred at 30 ± 2°C. Inactivation of suid herpesvirus, bovine viral diarrhoea virus and vesicular stomatitis virus was significantly lower at 5 ± 2°C than at higher temperatures. MB/light treatment affected clotting times and the activity of almost all investigated plasma proteins. Factor VIII (-17·7 ± 8·3%, 22 ± 2°C) and fibrinogen (-14·4 ± 16·4%, 22 ± 2°C) showed the highest decreases in activity. Increasing plasma temperatures resulted in greater changes in clotting time and higher losses of plasma coagulation factor activity. Temperature conditions for THERAFLEX MB-Plasma treatment must be carefully controlled to assure uniform quality of pathogen-reduced plasma in routine production. Inactivation of cooled plasma is not recommended. © 2018 International Society of Blood Transfusion.