Stamboulian, D; Lopardo, G; Lopez, P; Cortes-Barbosa, C; Valencia, A; Bedell, L; Karsten, A; Dull, P M
This study compared the investigational quadrivalent meningococcal CRM₁₉₇ conjugate vaccine, MenACWY-CRM, with licensed quadrivalent polysaccharide (MPSV4) and conjugate (MenACWY-D) meningococcal vaccines. In this phase III multicenter study, 2505 adults (aged 19-55 years) were randomized to receive either MenACWY-CRM or MenACWY-D, and 326 adults (aged 56-65 years) were randomized to receive either MenACWY-CRM or MPSV4. Sera obtained pre-vaccination and at 1-month post-vaccination were tested for serogroup-specific serum bactericidal activity using human complement (hSBA) for immunogenicity non-inferiority and superiority analyses. The vaccines in all groups were well tolerated. In the 19-55 years age group, post-vaccination geometric mean titers (GMTs) were consistently higher for MenACWY-CRM than for MenACWY-D for all four serogroups. MenACWY-CRM was non-inferior to MenACWY-D for all serogroups, and superior for serogroup Y. In the 56-65 years age group, post-vaccination GMTs were 1.2- to 5.4-fold higher for MenACWY-CRM than for MPSV4 for the four serogroups. MenACWY-CRM is well tolerated and immunogenic in adults aged 19-65 years, with at least non-inferior immunogenicity compared with the currently licensed meningococcal vaccines. Copyright © 2010 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
Lalwani, Sanjay; Agarkhedkar, Sharad; Gogtay, Nithya; Palkar, Sonali; Agarkhedkar, Shalaka; Thatte, Urmila; Vakil, Hoshang; Jonnalagedda, Rekha; Pedotti, Paola; Hoyle, Margaret; Bhusal, Chiranjiwi; Arora, Ashwani
This phase 3, multi-center, open-label study evaluated the immunogenicity and safety of a quadrivalent meningococcal conjugate vaccine (MenACWY-CRM, Menveo(®); Novartis Vaccines and Diagnostics S.r.l., Siena, Italy) in healthy Indian subjects aged 2-75 years, to provide data for licensure in India. A total of 180 subjects were enrolled (60 subjects 2-10 years, 60 subjects 11-18 years, and 60 subjects 19-75 years) and received one dose of MenACWY-CRM. Serum bactericidal activity with human complement (hSBA) was measured before and 1 month after vaccination. Adverse events were collected throughout the 29-day study period. Percentages of subjects with post-vaccination hSBA ≥8 were 72%, 95%, 94%, and 90% for serogroups A, C, W, and Y, respectively. Geometric mean titers rose 7-fold to 42-fold against the four serogroups. Similar immune responses were observed for the age subgroups 2-10 years, 11-18 years, and 19-75 years. Seroresponse rates at 1 month following vaccination were 72%, 88%, 55%, and 71% for serogroups A, C, W, and Y, respectively. The vaccine was well tolerated with no safety concerns. A single dose of MenACWY-CRM induced a robust immune response against all four meningococcal serogroups and was well tolerated in an Indian population 2-75 years of age. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.
Reisinger, Keith S; Baxter, Roger; Block, Stanley L; Shah, Jina; Bedell, Lisa; Dull, Peter M
Neisseria meningitidis is a leading cause of bacterial meningitis in the United States, with the highest case fatality rates reported for individuals > or = 15 years of age. This study compares the safety and immunogenicity of the Novartis Vaccines investigational quadrivalent meningococcal CRM(197) conjugate vaccine, MenACWY-CRM, to those of the licensed meningococcal conjugate vaccine, Menactra, when administered to healthy adults. In this phase III multicenter study, 1,359 adults 19 to 55 years of age were randomly assigned to one of four groups (1:1:1:1 ratio) to receive a single dose of one of three lots of MenACWY-CRM or a single dose of Menactra. Serum samples obtained at baseline and 1 month postvaccination were tested for serogroup-specific serum bactericidal activity using human complement (hSBA). The hSBA titers following vaccination with MenACWY-CRM and Menactra were compared in noninferiority and prespecified superiority analyses. Reactogenicity was similar in the MenACWY-CRM and Menactra groups, and neither vaccine was associated with a serious adverse event. When compared with Menactra, MenACWY-CRM met the superiority criteria for the proportions of recipients achieving a seroresponse against serogroups C, W-135, and Y and the proportion of subjects achieving postvaccination titers of > or = 1:8 for serogroups C and Y. MenACWY-CRM's immunogenicity was statistically noninferior (the lower limit of the two-sided 95% confidence interval was more than -10%) to that of Menactra for all four serogroups, with the postvaccination hSBA geometric mean titers being consistently higher for MenACWY-CRM than for Menactra. MenACWY-CRM is well tolerated in adults 19 to 55 years of age, with immune responses to each of the serogroups noninferior and, in some cases, statistically superior to those to Menactra.
Lee, Hoan Jong; Chung, Moon-Hyun; Kim, Woo Joo; Hong, Young Jin; Choi, Kyong Min; Lee, Jina; Oh, Chi Eun; Welsch, Jo Anne; Kim, Kyung-Hyo; Hong, Ki Bae; Dagnew, Alemnew F; Bock, Hans; Dull, Peter M; Odrljin, Tatjana
This phase III placebo-controlled study evaluated the immunogenicity and safety of MenACWY-CRM vaccination in healthy Korean adolescents and adults. Serum bactericidal activity with human complement (hSBA) was measured before and 1 month after vaccination against all four meningococcal serogroups. The IgG concentration specific for serogroup W capsular polysaccharide was measured in a subset of subjects in a post-hoc analysis. Adverse reactions were monitored throughout the study. Four hundred and fifty subjects were randomized 2:1 to receive MenACWY-CRM (N=297) or a saline placebo (N=153). MenACWY-CRM induced a good immune response against all four serogroups, with seroprotection rates (hSBA titers ≥8) of 79%, 99%, 98%, and 94% for serogroups A, C, W, and Y, respectively. Seroresponse rates were high for serogroups A, C, and Y, i.e. 76%, 86%, and 69%, respectively; the rate for serogroup W was 28%. MenACWY-CRM vaccine induced serum bactericidal antibodies against all four serogroups in a majority of subjects regardless of their baseline hSBA titers. MenACWY-CRM was generally well tolerated with most reactions being transient and mild to moderate in severity. Findings of this first study of a quadrivalent meningococcal polysaccharide conjugate vaccine in Korean adults and adolescents demonstrated that a single dose of MenACWY-CRM was well tolerated and immunogenic, as indicated by the percentages of subjects with hSBA titers ≥8 (79%, 99%, 98%, and 94% of subjects) and geometric mean titers (48, 231, 147, and 107) against serogroups A, C, W, and Y, respectively, at 1 month post-vaccination.
Hoan Jong Lee
Conclusions: Findings of this first study of a quadrivalent meningococcal polysaccharide conjugate vaccine in Korean adults and adolescents demonstrated that a single dose of MenACWY-CRM was well tolerated and immunogenic, as indicated by the percentages of subjects with hSBA titers ≥8 (79%, 99%, 98%, and 94% of subjects and geometric mean titers (48, 231, 147, and 107 against serogroups A, C, W, and Y, respectively, at 1 month post-vaccination.
Nolan, Terry M; Nissen, Michael D; Naz, Aftab; Shepard, Julie; Bedell, Lisa; Hohenboken, Matthew; Odrljin, Tatjana; Dull, Peter M
Infants are at the highest risk for meningococcal disease and a broadly protective and safe vaccine is an unmet need in this youngest population. We evaluated the immunogenicity and safety of a 4-dose infant/toddler regimen of MenACWY-CRM given at 2, 4, 6, and 12 months of age concomitantly with pentavalent diphtheria-tetanus-acellular pertussis-Hemophilus influenzae type b-inactivated poliovirus-combination vaccine (DTaP-IPV/Hib), hepatitis B vaccine (HBV), 7- or 13-valent conjugate pneumococcal vaccine (PCV), and measles, mumps, and rubella vaccine (MMR). Four doses of MenACWY-CRM induced hSBA titers ≥8 in 89%, 95%, 97%, and 96% of participants against serogroups A, C, W-135, and Y, respectively. hSBA titers ≥8 were present in 76-98% of participants after the first 3 doses. A categorical linear analysis incorporating vaccine group and study center showed responses to routine vaccines administered with MenACWY-CRM were non-inferior to routine vaccines alone, except for seroresponse to the pertussis antigen fimbriae. The reactogenicity profile was not affected when MenACWY-CRM was administered concomitantly with routine vaccines. MenACWY-CRM administered with routine concomitant vaccinations in young infants was well tolerated and induced highly immunogenic responses against each of the serogroups without significant interference with the immune responses to routine infant vaccinations. Healthy 2 month old infants were randomized to receive MenACWY-CRM with routine vaccines (n = 258) or routine vaccines alone (n = 271). Immunogenicity was assessed by serum bactericidal assay using human complement (hSBA). Medically attended adverse events (AEs), serious AEs (SAEs) and AEs leading to study withdrawal were collected throughout the study period.
Ilyina, Natalia; Kharit, Susanna; Namazova-Baranova, Leila; Asatryan, Asmik; Benashvili, Mayya; Tkhostova, Elmira; Bhusal, Chiranjiwi; Arora, Ashwani Kumar
Neisseria meningitidis is the leading cause of bacterial invasive infections in people aged safety of the quadrivalent meningococcal CRM197-conjugate vaccine MenACWY when administered to healthy Russian subjects aged 2 years and above. A total of 197 subjects were immunized with a single dose of the vaccine, and serogroup-specific serum bactericidal activity was measured pre and 1-month post-vaccination with human complement (hSBA) serum titers. Regardless of baseline serostatus, 1 month after a single dose of MenACWY-CRM197 85% (95%CI, 79-90%) of subjects showed serologic response against serogroup A, 74% (67-80%) against serogroup C, 60% (53-67%) against serogroup W, and 83% (77-88%) against serogroup Y. The percentage of subjects with hSBA titers ≥ 1:8 1 month after vaccination was 89% (83-93%) against serogroup A, 84% (78-89%) against serogroup C, 97% (93-99%) against serogroup W, and 88% (82-92%) against serogroup Y. Comparable results were obtained across all subjects: children (2 to 10 years), adolescents (11 to 17 years), and adults (≥18 years). The MenACWY-CRM197 vaccine showed an acceptable safety profile and was well tolerated across all age groups, with no serious adverse events or deaths reported during the study. In conclusion, a single dose of meningococcal MenACWY-CRM197 vaccine is immunogenic and has an acceptable safety profile, provides a broad protection against the most frequent epidemic serogroups, and is a suitable alternative to currently available unconjugated monovalent or bivalent polysaccharide vaccines in Russia.
Block, Stan L; Christensen, Shane; Verma, Bikash; Xie, Fang; Keshavan, Pavitra; Dull, Peter M; Smolenov, Igor
In a multi-center extension study, children 2-10 years of age, initially vaccinated with one or two doses (2-5 year-olds) or one dose (6-10 year-olds) of quadrivalent meningococcal CRM197-conjugate vaccine (MenACWY-CRM), were assessed five years later for antibody persistence and booster response using serum bactericidal assay with human complement (hSBA). Children 7-10 and 11-15 years of age, who received MenACWY-CRM in the original study, and age-matched vaccine-naïve children, were enrolled in this extension study. After an initial blood draw, children received one dose of MenACWY-CRM as booster or primary dose, with a second blood draw 28 days later. hSBA titers decreased five years after primary vaccination, but were higher than in non-vaccinated controls against serogroups C, W and Y, with substantial proportions having titers ≥8: 7-22% for A, 32-57% for C, 74-83% for W, and 48-54% for Y. Previously-vaccinated children demonstrated booster responses to revaccination against all four serogroups. Responses to primary vaccination in vaccine-naïve controls were lower and similar to primary responses observed in the original study. All vaccinations were generally well tolerated, with no safety concern raised. Approximately half the children vaccinated as 2-10 year-olds maintained protective antibodies against serogroups C, W and Y five years later, but fewer did against serogroup A. Declining titers five years after vaccination and robust booster responses suggest that five years may be an appropriate interval to revaccinate children, subject to epidemiology and delivery considerations. Copyright © 2015 Elsevier Ltd. All rights reserved.
Johnston, William; Essink, Brandon; Kirstein, Judith; Forleo-Neto, Eduardo; Percell, Sandra; Han, Linda; Keshavan, Pavitra; Smolenov, Igor
We compared the immunogenicity, safety and 1-year antibody persistence of a single-dose and a 2-dose series of a licensed meningococcal ACWY-CRM conjugate vaccine (MenACWY-CRM) in 2- to 10-year-old children. In this phase III, multicenter, observer-blind study, children aged 2-5 years (n = 359) and 6-10 years (n = 356) were randomized 1:1 to receive 2 doses of MenACWY-CRM (ACWY2) or 1 dose of placebo followed by 1 dose of MenACWY-CRM (ACWY1), 2 months apart. Immunogenicity was measured using serum bactericidal activity with human complement (hSBA). Primary outcomes were to assess the immunologic noninferiority and superiority of ACWY2 versus ACWY1. One-month after the second dose, the hSBA seroresponse in ACWY2 was noninferior to ACWY1 for all 4 serogroups, in both age cohorts, and was superior for serogroups C and Y in the 2- to 5-year-old age cohort and for serogroup Y in the 6- to 10-year-old age cohort. Overall, 90%-99% of subjects in ACWY2 and 65%-96% in ACWY1 had hSBA titers ≥ 8; geometric mean titers were 1.8- to 6.4-fold higher in ACWY2 than ACWY1 across serogroups. At 1 year postvaccination, geometric mean titers declined, and the differences between ACWY2 and ACWY1 remained significant for serogroups A and C in the 2- to 5-year-old age cohort and for serogroups C and Y in the 6- to 10-year-old age cohort. The safety profile of MenACWY-CRM was similar in both groups. The single dose and 2-dose MenACWY-CRM series were immunogenic and well tolerated. Although antibody responses were greater after 2 doses, especially in the 2- to 5-year-old age cohort, this difference was less pronounced at 1 year postvaccination.
Leonardi, Michael; Latiolais, Thomas; Sarpong, Kwabena; Simon, Michael; Twiggs, Jerry; Lei, Paul; Rinderknecht, Stephen; Blatter, Mark; Bianco, Veronique; Baine, Yaela; Friedland, Leonard R; Baccarini, Carmen; Miller, Jacqueline M
Co-administration of an investigational quadrivalent meningococcal serogroups A, C, W and Y tetanus toxoid conjugate vaccine (MenACWY-TT) with the fourth dose of diphtheria-tetanus-acellular pertussis vaccine (DTaP) at age 15-18 months was investigated in 3-dose Haemophilus influenzae type b-meningococcal serogroups C/Y conjugate vaccine (HibMenCY-TT)-primed toddlers. Infants were randomized (5:1) and primed at 2, 4 and 6 months of age with HibMenCY-TT and DTaP-hepatitis B-inactivated poliovirus (DTaP-HBV-IPV) vaccine, or Hib-TT and DTaP-HBV-IPV (Control). HibMenCY-TT+ DTaP-HBV-IPV vaccinees were re-randomized (2:2:1) to receive MenACWY-TT at 12-15 months and DTaP at 15-18 months (MenACWY-TT group); MenACWY-TT co-administered with DTaP at 15-18 months (Coad group); or HibMenCY-TT at 12-15 months and DTaP at 15-18 months (HibMenCY-TT group). Controls received DTaP at 15-18 months. Only children in the HibMenCY-TT group received a fourth dose of Hib conjugate vaccine due to Hib conjugate vaccine shortage at the time of the study. DTaP immunogenicity and reactogenicity were assessed one month post-vaccination. Pre-defined statistical non-inferiority criteria between Coad and Control groups were met for diphtheria, tetanus and filamentous haemagglutinin but not pertussis toxoid and pertactin. Following vaccination ≥99% of children had anti-diphtheria/anti-tetanus concentrations ≥1.0 IU/ml. Pertussis GMCs were lower in all investigational groups versus Control. In post hoc analyses, pertussis antibody concentrations were above those in infants following 3-dose DTaP primary vaccination in whom efficacy against pertussis was demonstrated (Schmitt, von König, et al., 1996; Schmitt, Schuind, et al., 1996). The reactogenicity profile of the Coad group was similar to DTaP administered alone. Routine booster DTaP was immunogenic with an acceptable safety profile when co-administered with MenACWY-TT vaccine in HibMenCY-TT-primed toddlers. These data support the
Safety of a quadrivalent meningococcal serogroups A, C, W and Y conjugate vaccine (MenACWY-CRM) administered with routine infant vaccinations: results of an open-label, randomized, phase 3b controlled study in healthy infants.
Abdelnour, Arturo; Silas, Peter E; Lamas, Marta Raquel Valdés; Aragón, Carlos Fernándo Grazioso; Chiu, Nan-Chang; Chiu, Cheng-Hsun; Acuña, Teobaldo Herrera; Castrejón, Tirza De León; Izu, Allen; Odrljin, Tatjana; Smolenov, Igor; Hohenboken, Matthew; Dull, Peter M
The highest risk for invasive meningococcal disease (IMD) is in infants aged CRM, a quadrivalent meningococcal conjugate vaccine, concomitantly administered with routine vaccinations to healthy infants. Two-month-old infants were randomized 3:1 to receive MenACWY-CRM with routine vaccines or routine vaccines alone at ages 2, 4, 6 and 12 months. Adverse events (AEs) that were medically attended and serious adverse events (SAEs) were collected from all subjects from enrollment through 18 months of age. In a subset, detailed safety data (local and systemic solicited reactions and all AEs) were collected for 7 days post vaccination. The primary objective was a non-inferiority comparison of the percentages of subjects with ≥1 severe systemic reaction during Days 1-7 after any vaccination of MenACWY-CRM plus routine vaccinations versus routine vaccinations alone (criterion: upper limit of 95% confidence interval [CI] of group difference CRM plus routine vaccines and 13% after routine vaccines alone (group difference 3.0% (95% CI -0.8, 6.4%). Although the non-inferiority criterion was not met, post hoc analysis controlling for significant center and group-by-center differences revealed that MenACWY-CRM plus routine vaccinations was non-inferior to routine vaccinations alone (group difference -0.1% [95% CI -4.9%, 4.7%]). Rates of solicited AEs, medically attended AEs, and SAEs were similar across groups. In a large multinational safety study, a 4-dose series of MenACWY-CRM concomitantly administered with routine vaccines was clinically acceptable with a similar safety profile to routine vaccines given alone. Copyright © 2013 Elsevier Ltd. All rights reserved.
Kim, Han Wool; Park, In Ho; You, Sooseong; Yu, Hee Tae; Oh, In Soo; Sung, Pil Soo; Shin, Eui Cheol; Kim, Kyung Hyo
The quadrivalent meningococcal conjugate vaccine (MenACWY-CRM) has been introduced for military recruits in Korea since 2012. This study was performed to evaluate the immunogenicity of MenACWY-CRM in Korean military recruits. In addition, the influence of tetanus-diphtheria toxoids (Td) vaccination on the vaccine response to MenACWY-CRM was analyzed. A total of 75 military recruits were enrolled. Among them, 18 received a dose of MenACWY-CRM only (group 1), and 57 received Td three days before MenACWY-CRM immunization (group 2). The immunogenicity of MenACWY-CRM was compared between the two groups. The serum bactericidal activity with baby rabbit complement was measured before and three weeks after immunization against serogroups A, C, W-135, and Y. The geometric mean titers (GMTs) against four serogroups were significantly increased in both groups after immunization. Compared to group 2, group 1 exhibited significantly higher vaccine responses in several aspects: post-immune GMTs against serogroup A and C, seroresponse rates against serogroup A, and a fold increases of titers against serogroup A, C, and Y. MenACWY-CRM was immunogenic against all vaccine-serogroups in Korean military recruits. Vaccine response to MenACWY-CRM was influenced by Td administered three days earlier.
Safety and immunogenicity of a four-component meningococcal group B vaccine (4CMenB) and a quadrivalent meningococcal group ACWY conjugate vaccine administered concomitantly in healthy laboratory workers.
Findlow, Jamie; Bai, Xilian; Findlow, Helen; Newton, Emma; Kaczmarski, Ed; Miller, Elizabeth; Borrow, Ray
Safety precautions for laboratory staff working with meningococci should primarily rely on laboratory procedures preventing exposure to aerosols containing viable meningococci. Despite this, vaccination is a key component of protection in the occupational setting. In the UK in 2009, there were no licensed vaccines for meningococcal capsular group B or conjugate vaccines for capsular groups A, C, W and Y. We therefore undertook a Phase II trial in laboratory workers to investigate the safety and immunogenicity of a four component group B vaccine (4CMenB) and a quadrivalent group A, C, W and Y conjugate vaccine (ACWY-CRM). Enrolment was open to staff aged 18-65 years at the Public Health Laboratory, Manchester who may have had a potential occupational exposure risk to meningococci. 4CMenB was administered at 0, 2 and 6 months in the non-dominant arm and ACWY-CRM concomitantly at 0 months in the dominant arm. Pre- and post-vaccination blood samples were taken and analysed by the serum bactericidal antibody (SBA) assay against A, C, W and Y strains and a panel of seven diverse group B strains. Diary cards were used to record any local and systemic reactions following each vaccination. In total, 38 staff were enrolled and received initial vaccinations with 31 completing the trial per protocol. Both vaccines were proven safe, with local reactogenicity being more commonly reported following 4CMenB than ACWY-CRM. High proportions of subjects had putative protective SBA titres pre-vaccination, with 61-84 and 61-87% protected against A, C, W and Y strains and diverse MenB strains, respectively. Post-vaccination, SBA titres increased with 95-100 and 90-100% of subjects with protective SBA titres against A, C, W and Y strains and diverse MenB strains, respectively. These data suggest that 4CMenB and ACWY-CRM are safe when administered concomitantly and have the potential to enhance protection for laboratory workers. www.clinicaltrials.gov identifier: NCT00962624. Crown
Meningococcal serogroup C immunogenicity, antibody persistence and memory B-cells induced by the monovalent meningococcal serogroup C versus quadrivalent meningococcal serogroup ACWY conjugate booster vaccine: A randomized controlled trial.
van Ravenhorst, Mariëtte B; van der Klis, Fiona R M; van Rooijen, Debbie M; Knol, Mirjam J; Stoof, Susanne P; Sanders, Elisabeth A M; Berbers, Guy A M
Adolescents are considered the key transmitters of meningococci in the population. Meningococcal serogroup C (MenC) antibody levels wane rapidly after MenC conjugate vaccination in young children, leaving adolescents with low antibody levels. In this study, we compared MenC immune responses after booster vaccination in adolescence with either tetanus toxoid conjugated MenC (MenC-TT) or MenACWY (MenACWY-TT) vaccine, and aimed to establish an optimal age for this booster. Healthy 10-, 12-, and 15-year-olds, who received a single dose of MenC-TT vaccine in early childhood, were randomized to receive MenC-TT or MenACWY-TT vaccine. MenC serum bactericidal antibody (rSBA) titers, MenC polysaccharide (PS) specific IgG, IgG1 and IgG2 and MenC-specific IgG and IgA memory B-cells were determined before, one month and one year after the booster. Non-inferiority was tested by comparing geometric mean titers (GMTs) between vaccinees at one year. Of 501 participants, 464 (92.6%) were included in the 'according to protocol' cohort analysis. At one month, all participants developed high MenC rSBA titers (>24,000 in all groups) and MenC-PS-specific IgG levels. Non-inferiority was not demonstrated one year after the booster with higher MenC GMTs after the monovalent vaccine, but 462/464 (99.6%) participants maintained protective MenC rSBA titers. IgG levels mainly consisted of IgG1, but similar levels of increase were observed for IgG1 and IgG2. Both vaccines induced a clear increase in the number of circulating MenC-PS specific IgG and IgA memory B-cells. Between one month and one year, the highest antibody decay rate was observed in the 10-year-olds. Both MenC-TT and MenACWY-TT vaccines induced robust protective MenC immune responses after the booster vaccination, although non-inferiority could not be demonstrated for the MenACWY-TT vaccine after one year. Our results underline the importance of optimal timing of a meningococcal booster vaccination to protect against MenC disease
Huang, Li-Min; Chiu, Nan-Chang; Yeh, Shu-Jen; Bhusal, Chiranjiwi; Arora, Ashwani Kumar
MenACWY-CRM (Menveo®, Novartis Vaccines, Siena, Italy) is a quadrivalent meningococcal conjugate vaccine developed to help prevent invasive meningococcal disease caused by Neisseria meningitidis serogroups A, C, W, and Y. It is approved within the European Union in persons >2 years of age and in persons from 2 months to 55 years of age in the United States, among other countries. Little is known about the immunogenicity and safety of this vaccine in Taiwanese children >2 years and adolescents. This study assessed the immunogenicity and safety of a single injection of MenACWY-CRM vaccine in Taiwanese subjects aged 2-18 years old. In this phase III, multicentre, open-label study 341 subjects received one dose of MenACWY-CRM. Immunogenicity measures were rates of seroresponse (defined as the proportion of subjects with a postvaccination hSBA ≥1:8 if the prevaccination (baseline) titre was CRM vaccination at Day 29 for the serogroups A, C, W, and Y were 83%, 93%, 50%, and 65%, respectively. At Day 29 the percentages of subjects with hSBA ≥1:8 against all four serogroups A, C, W and Y were: 83%, 96%, 96% and 82%, respectively. GMTs against all serogroups rose by ≥7-fold from baseline to Day 29. The vaccine was well tolerated. A single dose of MenACWY-CRM demonstrated a robust immune response, and an acceptable safety profile in Taiwanese children and adolescents. Copyright © 2014 Elsevier Ltd. All rights reserved.
Quadrivalent meningococcal (MenACWY-TT) conjugate vaccine or a fourth dose of H. influenzae-N. meningitidis C/Y conjugate vaccine (HibMenCY-TT) is immunogenic in toddlers who previously received three doses of HibMenCY-TT in infancy.
Leonardi, Michael; Latiolais, Thomas; Sarpong, Kwabena; Simon, Michael; Twiggs, Jerry; Lei, Paul; Rinderknecht, Stephen; Blatter, Mark; Bianco, Veronique; Baine, Yaela; Friedland, Leonard R; Miller, Jacqueline M
Immunogenicity and safety of a single dose of MenACWY-TT or a fourth dose of HibMenCY-TT were evaluated in the second year of life in HibMenCY-TT-primed toddlers. Healthy infants were randomized (5:1) and primed at 2, 4 and 6 months of age with HibMenCY-TT and diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus (DTaP-HBV-IPV) vaccine; or Hib-TT and DTaP-HBV-IPV (control). Recipients of HibMenCY-TT+DTaP-HBV-IPV were re-randomized (2:2:1) to receive MenACWY-TT at 12-15 months and DTaP at 15-18 months; MenACWY-TT co-administered with DTaP at 15-18 months; or HibMenCY-TT at 12-15 months and DTaP at 15-18 months. Controls received DTaP only at 15-18 months due to Hib conjugate vaccine shortage. Serum bactericidal activity using human complement (hSBA) and safety were assessed one month after meningococcal vaccination. After vaccination with MenACWY-TT at 12-15 months or MenACWY-TT+DTaP at 15-18 months, all subjects previously primed for serogroups C/Y had hSBA ≥1:8 for these serogroups. At least 96.1% also had hSBA ≥1:8 for serogroups A/W. All subjects in the HibMenCY-TT group had hSBA ≥1:8 for serogroups C/Y. All pre-defined statistical criteria for meningococcal immunogenicity were satisfied. All vaccination regimens had acceptable safety profiles. Children primed with three doses of HibMenCY-TT who then received a single dose of MenACWY-TT or a fourth dose of HibMenCY-TT had robust increases in hSBA titers for serogroups C/Y. These data provide support that MenACWY-TT, given with or without the fourth scheduled dose of DTaP could be administered as an alternative to a fourth dose of HibMenCY-TT in the second year of life. This study (110870/110871) is registered at www.clinicaltrials.gov NCT00614614. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.
Randomized trial on the safety, tolerability, and immunogenicity of MenACWY-CRM, an investigational quadrivalent meningococcal glycoconjugate vaccine, administered concomitantly with a combined tetanus, reduced diphtheria, and acellular pertussis vaccine in adolescents and young adults.
Gasparini, Roberto; Conversano, Michele; Bona, Gianni; Gabutti, Giovanni; Anemona, Alessandra; Dull, Peter M; Ceddia, Francesca
This study evaluated the safety, tolerability, and immunogenicity of an investigational quadrivalent meningococcal conjugate vaccine, MenACWY-CRM, when administered concomitantly with a combined tetanus, reduced diphtheria, and acellular pertussis (Tdap) vaccine, in subjects aged 11 to 25 years. Subjects received either MenACWY-CRM and Tdap, MenACWY-CRM and saline placebo, or Tdap and saline placebo. No significant increase in reactogenicity and no clinically significant vaccine-related adverse events (AEs) occurred when MenACWY-CRM and Tdap were administered concomitantly. Similar immunogenic responses to diphtheria, tetanus, and meningococcal (serogroups A, C, W-135, and Y) antigens were observed, regardless of concomitant vaccine administration. Antipertussis antibody responses were comparable between vaccine groups for filamentous hemagglutinin and were slightly lower, although not clinically significantly, for pertussis toxoid and pertactin when the two vaccines were administered concomitantly. These results indicate that the investigational MenACWY-CRM vaccine is well tolerated and immunogenic and that it can be coadministered with Tdap to adolescents and young adults.
Miller, Jacqueline M.; Mesaros, Narcisa; Van Der Wielen, Marie; Baine, Yaela
Meningococcal diseases are serious threats to global health, and new vaccines specifically tailored to meet the age-related needs of various geographical areas are required. This paper focuses on the meningococcal conjugate vaccines developed by GSK Biologicals. Two combined conjugate vaccines were developed to help protect infants and young children in countries where the incidence of meningococcal serogroup C or serogroup C and Y disease is important: Hib-MenC-TT vaccine, which offers protection against Haemophilus influenzae type b and Neisseria meningitidis serogroup C diseases, is approved in several countries; and Hib-MenCY-TT vaccine, which adds N. meningitidis serogroup Y antigen, is currently in the final stages of development. Additionally, a tetravalent conjugate vaccine (MenACWY-TT) designed to help protect against four meningococcal serogroups is presently being evaluated for global use in all age groups. All of these vaccines were shown to be highly immunogenic and to have clinically acceptable safety profiles. PMID:21991444
Jacqueline M. Miller
Full Text Available Meningococcal diseases are serious threats to global health, and new vaccines specifically tailored to meet the age-related needs of various geographical areas are required. This paper focuses on the meningococcal conjugate vaccines developed by GSK Biologicals. Two combined conjugate vaccines were developed to help protect infants and young children in countries where the incidence of meningococcal serogroup C or serogroup C and Y disease is important: Hib-MenC-TT vaccine, which offers protection against Haemophilus influenzae type b and Neisseria meningitidis serogroup C diseases, is approved in several countries; and Hib-MenCY-TT vaccine, which adds N. meningitidis serogroup Y antigen, is currently in the final stages of development. Additionally, a tetravalent conjugate vaccine (MenACWY-TT designed to help protect against four meningococcal serogroups is presently being evaluated for global use in all age groups. All of these vaccines were shown to be highly immunogenic and to have clinically acceptable safety profiles.
Alberer, Martin; Burchard, Gerd; Jelinek, Tomas; Reisinger, Emil; Beran, Jiri; Meyer, Seetha; Forleo-Neto, Eduardo; Gniel, Dieter; Dagnew, Alemnew F; Arora, Ashwani Kumar
Potential interactions between vaccines may compromise the immunogenicity and/or safety of individual vaccines so must be assessed before concomitant administration is recommended. In this study, the immunogenicity and safety of travel vaccines against Japanese encephalitis (JEV) and rabies (PCECV) administered together with or without a quadrivalent meningococcal glycoconjugate ACWY-CRM vaccine were evaluated (NCT01466387). Healthy adults aged 18 to ≤60 years were randomized to one of four vaccine regimens: JEV + PCECV + MenACWY-CRM, JEV + PCECV, PCECV or MenACWY-CRM. Immunogenicity at baseline and 28 days post-complete vaccination was assessed by serum bactericidal assay using human complement or neutralization tests. Adverse events (AEs) were collected throughout the study period. JEV + PCECV + MenACWY-CRM was non-inferior to JEV + PCECV. Post-vaccination seroprotective neutralizing titers or concentrations were achieved in 98-99% (JE) and 100% (rabies) of subjects across the vaccine groups. Antibody responses to vaccine meningococcal serogroups were in the same range for MenACWY-CRM and JEV + PCECV + MenACWY-CRM. Rates of reporting of AEs were similar for JEV + PCECV and JEV + PCECV + MenACWY-CRM. MenACWY-CRM was administered with an inactivated adjuvanted JE and a purified chick embryo cell-culture rabies vaccine without compromising immunogenicity or safety of the individual vaccines. These data provide evidence that MenACWY-CRM could be effectively incorporated into travel vaccination programs. NCT01466387. Copyright © 2014 Elsevier Ltd. All rights reserved.
Safety and immunogenicity of one dose of MenACWY-CRM, an investigational quadrivalent meningococcal glycoconjugate vaccine, when administered to adolescents concomitantly or sequentially with Tdap and HPV vaccines.
Arguedas, A; Soley, C; Loaiza, C; Rincon, G; Guevara, S; Perez, A; Porras, W; Alvarado, O; Aguilar, L; Abdelnour, A; Grunwald, U; Bedell, L; Anemona, A; Dull, P M
This Phase III study evaluates an investigational quadrivalent meningococcal CRM(197) conjugate vaccine, MenACWY-CRM (Novartis Vaccines), when administered concomitantly or sequentially with two other recommended adolescent vaccines; combined tetanus, reduced diphtheria and acellular pertussis (Tdap), and human papillomavirus (HPV) vaccine. In this single-centre study, 1620 subjects 11-18 years of age, were randomized to three groups (1:1:1) to receive MenACWY-CRM concomitantly or sequentially with Tdap and HPV. Meningococcal serogroup-specific serum bactericidal assay using human complement (hSBA), and antibodies to Tdap antigens and HPV virus-like particles were determined before and 1 month after study vaccinations. Proportions of subjects with hSBA titres > or =1:8 for all four meningococcal serogroups (A, C, W-135, Y) were non-inferior for both concomitant and sequential administration. Immune responses to Tdap and HPV antigens were comparable when these vaccines were given alone or concomitantly with MenACWY-CRM. All vaccines were well tolerated; concomitant or sequential administration did not increase reactogenicity. MenACWY-CRM was well tolerated and immunogenic in subjects 11-18 years of age, with comparable immune responses to the four serogroups when given alone or concomitantly with Tdap or HPV antigens. This is the first demonstration that these currently recommended adolescent vaccines could be administered concomitantly without causing increased reactogenicity. Copyright 2010 Elsevier Ltd. All rights reserved.
Bona, Gianni; Castiglia, Paolo; Zoppi, Giorgio; de Martino, Maurizio; Tasciotti, Annaelisa; D'Agostino, Diego; Han, Linda; Smolenov, Igor
MenACWY-CRM (Menveo(®); GlaxoSmithKline) and MenACWY-TT (Nimenrix(®); Pfizer) are two meningococcal vaccines licensed in the European Union for use in both children and adults. While both vaccines target meningococcal serogroups A, C, W and Y, immunogenicity and reactogenicity of these quadrivalent meningococcal conjugate vaccines may differ due to differences in formulation processes and chemical structure. Yet data on the comparability of these two vaccines are limited. The reactogenicity and immunogenicity of one dose of either MenACWY-CRM or MenACWY-TT were evaluated in healthy toddlers aged 12-15 months. Immunogenicity was assessed using serum bactericidal antibody assays (SBA) with human (hSBA) and rabbit (rSBA) complement. A total of 202 children aged 12-15 months were enrolled to receive one dose of MenACWY-CRM or MenACWY-TT. Similar numbers of subjects reported solicited reactions within 7 days following either vaccination. Tenderness at the injection site was the most common local reaction. Systemic reactions reported were similar for both vaccines and mostly mild to moderate in severity: irritability, sleepiness and change in eating habits were most commonly reported. Immunogenicity at 1 month post-vaccination was generally comparable for both vaccines across serogroups. At 6 months post-vaccination antibody persistence against serogroups C, W, and Y was substantial for both vaccines, as measured by both assay methodologies. For serogroup A, hSBA titers declined in both groups, while rSBA titers remained high. Despite differences in composition, the MenACWY-CRM and MenACWY-TT vaccines have comparable reactogenicity and immunogenicity profiles. Immediate immune responses and short-term antibody persistence were largely similar between groups. Both vaccines were well-tolerated and no safety concerns were identified. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.
Gasparini, Roberto; Tregnaghi, Miguel; Keshavan, Pavitra; Ypma, Ellen; Han, Linda; Smolenov, Igor
Given the broad age range across which the quadrivalent meningococcal conjugate vaccine MenACWY-CRM is used, coadministration with routine vaccines should be evaluated across age groups for possible immunologic interference and impact on vaccine reactogenicity and safety. We summarize data from a large population of infants, adolescents and international travelers from 10 phase 3 or 4 clinical studies to evaluate coadministration of MenACWY-CRM with commonly administered vaccines. Noninferiority analyses of immune responses were performed across studies and age groups for each vaccine. Reactogenicity and safety were also assessed. In infants, MenACWY-CRM coadministered with routine vaccines did not reduce immune responses to diphtheria, tetanus, poliovirus, hepatitis B, Haemophilus influenzae type b, pneumococcal conjugate, measles-mumps-rubella, varicella or pertussis antigens. Noninferiority criteria were not met for some pneumococcal conjugate serotypes at 7 months of age, but no consistent trends were observed. In adolescents, coadministration did not reduce immune responses to tetanus, diphtheria and human papilloma virus vaccine antigens. Noninferiority criteria for pertussis antigens were not uniformly met in infant and adolescent studies, although the clinical relevance is unclear. In adults, coadministration did not reduce immune responses to hepatitis A/B, typhoid fever, yellow fever, Japanese encephalitis and rabies antigens. Immune responses to MenACWY-CRM were not impacted by coadministration of commonly administered vaccines. Coadministration did not increase frequencies of postvaccination adverse events in any age group. With no clinically relevant vaccine interactions or impact on vaccine reactogenicity or safety, these results support the coadministration of MenACWY-CRM with routine vaccines in all age groups.
Hepkema, Hiltsje; Pouwels, Koen B.; van der Ende, Arie; Westra, Tjalke A.; Postma, Maarten J.
In 2002, vaccination with a serogroup C meningococcal conjugate vaccine (MenC) was introduced in the Netherlands for all children aged 14 months. Despite its success, herd immunity may wane over time. Recently, a serogroup A,C,W135,Y meningococcal conjugate vaccine (MenACWY) was licensed for use in
Hepkema, Hiltsje; Pouwels, Koen B.; van der Ende, Arie; Westra, Tjalke A.; Postma, Maarten J.
Background: In 2002, vaccination with a serogroup C meningococcal conjugate vaccine (MenC) was introduced in the Netherlands for all children aged 14 months. Despite its success, herd immunity may wane over time. Recently, a serogroup A,C,W-135, Y meningococcal conjugate vaccine (MenACWY) was
MacNeil, Jessica R; Rubin, Lorry; McNamara, Lucy; Briere, Elizabeth C; Clark, Thomas A; Cohn, Amanda C
During its October 2013 meeting, the Advisory Committee on Immunization Practices (ACIP) recommended use of a third meningococcal conjugate vaccine, MenACWY-CRM (Menveo, Novartis), as an additional option for vaccinating infants aged 2 through 23 months at increased risk for meningococcal disease. MenACWY-CRM is the first quadrivalent meningococcal conjugate vaccine licensed for use in children aged 2 through 8 months. MenACWY-D (Menactra, Sanofi Pasteur) is recommended for use in children aged 9 through 23 months who are at increased risk for meningococcal disease, and Hib-MenCY-TT (MenHibrix, GlaxoSmithKline) is recommended for use in children aged 6 weeks through 18 months at increased risk. This report summarizes information on MenACWY-CRM administration in infants and provides recommendations for vaccine use in infants aged 2 through 23 months who are at increased risk for meningococcal disease. Because the burden of meningococcal disease in infants is low in the United States and the majority of cases that do occur are caused by serogroup B, which is not included in any vaccine licensed in the United States, only those infants who are at increased risk for meningococcal disease are recommended to receive a meningococcal vaccine.
Randomized Trial to Compare the Immunogenicity and Safety of a CRM or TT Conjugated Quadrivalent Meningococcal Vaccine in Teenagers who Received a CRM or TT Conjugated Serogroup C Vaccine at Preschool Age.
Ishola, David A; Andrews, Nick; Waight, Pauline; Yung, Chee-Fu; Southern, Jo; Bai, Xilian; Findlow, Helen; Matheson, Mary; England, Anna; Hallis, Bassam; Findlow, Jamie; Borrow, Ray; Miller, Elizabeth
Protection after meningococcal C (MenC) conjugate (MCC) vaccination in early childhood is short-lived. Boosting with a quadrivalent vaccine in teenage years, a high-risk period for MenC disease, should protect against additional serogroups but might compromise MenC response. The carrier protein in the primary MCC vaccine determines the response to MCC booster in toddlers, but the relationship between primary vaccine and booster given later is unclear. This study compared responses to a CRM-conjugated or tetanus toxoid (TT)-conjugated MenACWY vaccine in teenagers primed with different MCC vaccines at preschool age. Ninety-three teenagers (16-19 years), who were previously randomized at age 3-6 years to receive single-dose MCC-CRM or MCC-TT, were randomized to receive either MenACWY-CRM or MenACWY-TT booster. Serum bactericidal antibodies (SBA, protective titer ≥ 8) were measured before, 1 month and 6 or 9 months after boosting. Preboosting, MCC-TT-primed teenagers had significantly higher MenC SBA titers than those MCC-CRM-primed (P = 0.02). Postboosting, both MenACWY vaccines induced protective SBA titers to all 4 serogroups in most participants (≥ 98% at 1 month and ≥ 90% by 9 months postboost). The highest MenC SBA titers were seen in those MCC-TT-primed and MenACWY-TT-boosted [geometric mean titer (GMT) ~ 22,000] followed by those boosted with MenACWY-CRM irrespective of priming (GMT ~ 12,000) and then those MCC-CRM-primed and MenACWY-TT-boosted (GMT ~ 5500). The estimated postbooster MenC SBA decline beyond 1 month was ~40% as time since booster doubles. Both vaccines were well tolerated with no attributable serious adverse events. Both MenACWY vaccines safely induced protective sustained antibody responses against all targeted serogroups in MCC-primed teenagers.
Read, Robert C; Baxter, David; Chadwick, David R; Faust, Saul N; Finn, Adam; Gordon, Stephen B; Heath, Paul T; Lewis, David J M; Pollard, Andrew J; Turner, David P J; Bazaz, Rohit; Ganguli, Amitava; Havelock, Tom; Neal, Keith R; Okike, Ifeanyichukwu O; Morales-Aza, Begonia; Patel, Kamlesh; Snape, Matthew D; Williams, John; Gilchrist, Stefanie; Gray, Steve J; Maiden, Martin C J; Toneatto, Daniela; Wang, Huajun; McCarthy, Maggie; Dull, Peter M; Borrow, Ray
Meningococcal conjugate vaccines protect individuals directly, but can also confer herd protection by interrupting carriage transmission. We assessed the effects of meningococcal quadrivalent glycoconjugate (MenACWY-CRM) or serogroup B (4CMenB) vaccination on meningococcal carriage rates in 18-24-year-olds. In this phase 3, observer-blind, randomised controlled trial, university students aged 18-24 years from ten sites in England were randomly assigned (1:1:1, block size of three) to receive two doses 1 month apart of Japanese Encephalitis vaccine (controls), 4CMenB, or one dose of MenACWY-CRM then placebo. Participants were randomised with a validated computer-generated random allocation list. Participants and outcome-assessors were masked to the treatment group. Meningococci were isolated from oropharyngeal swabs collected before vaccination and at five scheduled intervals over 1 year. Primary outcomes were cross-sectional carriage 1 month after each vaccine course. Secondary outcomes included comparisons of carriage at any timepoint after primary analysis until study termination. Reactogenicity and adverse events were monitored throughout the study. Analysis was done on the modified intention-to-treat population, which included all enrolled participants who received a study vaccination and provided at least one assessable swab after baseline. This trial is registered with ClinicalTrials.gov, registration number NCT01214850. Between Sept 21 and Dec 21, 2010, 2954 participants were randomly assigned (987 assigned to control [984 analysed], 979 assigned to 4CMenB [974 analysed], 988 assigned to MenACWY-CRM [983 analysed]); 33% of the 4CMenB group, 34% of the MenACWY-CRM group, and 31% of the control group were positive for meningococcal carriage at study entry. By 1 month, there was no significant difference in carriage between controls and 4CMenB (odds ratio 1·2, 95% CI 0·8-1·7) or MenACWY-CRM (0·9, [0·6-1·3]) groups. From 3 months after dose two, 4CMen
Alberer, Martin; Burchard, Gerd; Jelinek, Tomas; Reisinger, Emil; Beran, Jiri; Hlavata, Lucie Cerna; Forleo-Neto, Eduardo; Dagnew, Alemnew F; Arora, Ashwani K
Compact and short pre-travel immunization schedules, which include several vaccinations in a single visit, are desirable for many travelers. However, concomitant vaccination could potentially compromise immunogenicity and/or safety of the individual vaccines and, therefore, possible vaccine interferences should be carefully assessed. This article discusses the immunogenicity and safety of travel vaccines for typhoid fever (TF) and yellow fever (YF), when administered with or without a quadrivalent meningococcal glycoconjugate ACWY-CRM vaccine (MenACWY-CRM). Healthy adults (18-≤60 years) were randomized to one of three vaccine regimens: TF + YF + MenACWY-CRM (group I; n = 100), TF + YF (group II; n = 101), or MenACWY-CRM (group III; n = 100). Immunogenicity at baseline and 4 weeks post-vaccination (day 29) was assessed by serum bactericidal assay using human complement (hSBA), enzyme-linked immunosorbent assay (ELISA), or a neutralization test. Adverse events (AEs) and serious adverse events (SAEs) were collected throughout the study period. Non-inferiority of post-vaccination geometric mean concentrations (GMCs) and geometric mean titers (GMTs) was established for TF and YF vaccines, respectively, when given concomitantly with MenACWY-CRM vaccine versus when given alone. The percentages of subjects with seroprotective neutralizing titers against YF on day 29 were similar in groups I and II. The antibody responses to meningococcal serogroups A, C, W-135, and Y were within the same range when MenACWY-CRM was given separately or together with TF and YF vaccines. The percentage of subjects reporting AEs was the same for TF and YF vaccines with or without MenACWY-CRM vaccine. There were no reports of SAEs or AEs leading to study withdrawals. These data provide evidence that MenACWY-CRM can be administered with typhoid Vi polysaccharide vaccine and live attenuated YF vaccine without compromising antibody responses stimulated by the
Tregnaghi, Miguel; Lopez, Pio; Stamboulian, Daniel; Graña, Gabriela; Odrljin, Tatjana; Bedell, Lisa; Dull, Peter M
This phase III study assessed the safety and immunogenicity of MenACWY-CRM, a quadrivalent meningococcal conjugate vaccine, administered with routine vaccines starting at 2 months of age. Healthy infants received MenACWY-CRM in a two- or three-dose primary infant series plus a single toddler dose. In addition, a two-dose toddler catch-up series was evaluated. Immune responses to MenACWY-CRM were assessed for serum bactericidal activity with human complement (hSBA). Reactogenicity and safety results were collected systematically. After a full infant/toddler series or two-dose toddler catch-up series, MenACWY-CRM elicited immune responses against the four serogroups in 94-100% of subjects. Noninferiority of the two- versus three-dose MenACWY-CRM infant dosing regimen was established for geometric mean titers for all serogroups. Following the three-dose infant primary series, 89-98% of subjects achieved an hSBA ≥ 8 across all serogroups. Immune responses to concomitant routine vaccines given with MenACWY-CRM were noninferior to responses to routine vaccines alone, except for pertactin after the two-dose infant series. Noninferiority criteria were met for all concomitant antigens after the three-dose infant series. MenACWY-CRM vaccination regimens in infants and toddlers were immunogenic and well tolerated. No clinically meaningful effects of concomitant administration with routine infant and toddler vaccines were observed. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.
Alberer, Martin; Burchard, Gerd; Jelinek, Tomas; Reisinger, Emil C; Meyer, Seetha; Forleo-Neto, Eduardo; Dagnew, Alemnew F; Arora, Ashwani Kumar
This phase 3b randomized, open-label study evaluated the immunogenicity and safety of coadministration of a hepatitis A and/or B vaccine with a quadrivalent oligosaccharide meningococcal CRM197 -conjugate vaccine (MenACWY-CRM), in the context of an accelerated hepatitis A and/or B immunization schedule. A total of 252 healthy adult subjects were randomized to three groups to receive hepatitis A/B only (HepA/B), hepatitis A/B coadministered with MenACWY-CRM (HepA/B+MenACWY-CRM), or MenACWY-CRM only (MenACWY-CRM). Hepatitis A and/or B vaccination was administered in the form of a single booster dose or a primary three-dose series, depending on the hepatitis A and/or B vaccination history of subjects. Antibody responses to hepatitis A/B vaccination were assessed 1 month following the last hepatitis A and/or B dose. Serum bactericidal activity with human complement (hSBA) against meningococcal serogroups A, C, W-135, and Y was assessed 1 month post-MenACWY-CRM vaccination. Safety was monitored throughout the study. At 1 month following the final hepatitis A and/or B vaccination, concomitant administration of hepatitis A/B and MenACWY-CRM was non-inferior to administration of hepatitis A/B alone in terms of geometric mean concentrations of antibodies against the hepatitis A and B antigens. One month post-MenACWY-CRM vaccination, the percentages of subjects achieving hSBA titers ≥8 for serogroups A, C, W-135, and Y in the HepA/B+MenACWY-CRM group (76, 87, 99, and 94%, respectively) were comparable to those in the MenACWY-CRM group (67, 82, 96, and 88%, respectively). The percentages of subjects reporting adverse events (AEs) were similar across study groups and a majority of the reported AEs were mild to moderate in nature. There were no study vaccine-related serious AEs. MenACWY-CRM can be administered concomitantly with a hepatitis A and/or B vaccine in the context of an accelerated hepatitis A and/or B immunization schedule without increasing safety concerns
Blanchard-Rohner, Geraldine; Snape, Matthew D; Kelly, Dominic F; O'Connor, Daniel; John, Tessa; Clutterbuck, Elizabeth A; Ohene-Kena, Brigitte; Klinger, Chaam L; Odrljin, Tatjana; Pollard, Andrew J
A quadrivalent meningococcal vaccine conjugated to CRM197 (MenACWY-CRM197) is immunogenic in young infants. We assessed the memory B-cell and antibody responses after a primary and booster course of MenACWY-CRM197 in children. At 5 months of age, following primary immunisation, serogroup-specific memory B-cells were detectable in fewer than 25% of children, although protective antibody titres (hSBA ≥ 4) were detectable in 69% of children against serogroup A and more than 95% against the other serogroups. At 12 months, before booster immunisation the percentages with hSBA ≥ 4 were 5% for serogroup A, and between 44 and 70% for the other serogroups. One month after booster immunisation with MenACWY-CRM197 over 50% of children had detectable memory B-cells, and 91% had hSBA ≥ 4 against serogroup A and more than 99% against the other serogroups. These data show that few antigen-specific anticapsular memory B-cells can be detected after two-doses priming with MenACWY-CRM197. For MenC and CRM197, the antigens with the highest number of B-cells at 5 months, there was a definite (p ≤0 .02) but weak correlation with antibody persistence at 12 months. Although previous studies suggest that measuring memory B-cell responses after priming immunisations in infancy can be used to predict antibody persistence and memory responses, this may not be suitable for all antigens in young children. Copyright © 2013 Elsevier Ltd. All rights reserved.
Tartof, Sara Yee; Sy, Lina S; Ackerson, Bradley K; Hechter, Rulin C; Haag, Mendel; Slezak, Jeffrey M; Luo, Yi; Fischetti, Christine A; Takhar, Harp S; Miao, Yan; Solano, Zendi; Jacobsen, Steven J; Tseng, Hung-Fu
Quadrivalent meningococcal conjugate vaccine is recommended for children, adolescents and adults at increased risk of meningococcal disease. In 2011, MenACWY-CRM (Menveo, GSK, Siena, Italy) was approved for children 2-10 years of age in the United States. Although no safety concerns arose from clinical trials, it remains important to monitor its safety in routine clinical settings. Kaiser Permanente Southern California members 2-10 years old who received MenACWY-CRM between September 2011 and September 2014 were included. Electronic health records were searched using a validated algorithm to identify 26 prespecified events of interests (EOIs) and serious medically attended events (SMAEs) from inpatient or emergency settings up to 1 year after MenACWY-CRM vaccination. SMAEs were categorized by International Classification of Diseases, 9th revision diagnostic categories. All events were reviewed to confirm the diagnosis and symptom onset date. The study was descriptive (NCT01452438); no statistical tests were performed. Among 387 vaccinated children, 327 with ≥6 months membership before vaccination were analyzed. Among EOIs, 9 asthma cases and 1 myasthenia gravis case underwent chart review which confirmed 1 incident asthma case occurring 237 days after concomitant vaccination with MenACWY-CRM and typhoid vaccine. Thirty-one children experienced SMAEs, most commonly because of unrelated injury and poisoning. The remaining events occurred sporadically after vaccination and most were unlikely related to vaccination based on medical record review. One incident EOI of asthma late in the 1-year observation period and sporadic distribution of SMAEs were observed. These data do not suggest safety concerns associated with MenACWY-CRM vaccination in children 2-10 years old.
Full Text Available BACKGROUND: In 2002, vaccination with a serogroup C meningococcal conjugate vaccine (MenC was introduced in the Netherlands for all children aged 14 months. Despite its success, herd immunity may wane over time. Recently, a serogroup A,C,W135,Y meningococcal conjugate vaccine (MenACWY was licensed for use in subjects of 12 months of age and above. OBJECTIVES: To evaluate the cost-effectiveness of meningococcal vaccination at 14 months and an additional vaccination at the age of 12 years, both with the MenACWY vaccine. METHODS: A decision analysis cohort model, with 185,000 Dutch newborns, was used to evaluate the cost-effectiveness of different immunization strategies. For strategies including a vaccination at 12 years of age, an additional cohort with adolescents aged 12 years was followed. The incremental cost-effectiveness ratio (ICER was estimated for the current disease incidence and for a scenario when herd immunity is lost. RESULTS: Vaccination with MenACWY at 14 months is cost-saving. Vaccinating with MenACWY at 14 months and at 12 years would prevent 7 additional cases of meningococcal serogroup A,C,W135,Y disease in the birth cohort and adolescent cohort followed for 99 years compared to the current vaccine schedule of a single vaccination with MenC at 14 months. With the current incidence, this strategy resulted in an ICER of €635,334 per quality adjusted life year. When serogroup C disease incidence returns to pre-vaccination levels due to a loss of vaccine-induced herd-immunity, vaccination with MenACWY at 14 months and at 12 years would be cost-saving. CONCLUSIONS: Routine vaccination with MenACWY is cost-saving. With the current epidemiology, a booster-dose with MenACWY is not likely cost-effective. When herd immunity is lost, a booster-dose has the potential of being cost-effective. A dynamic model should be developed for more precise estimation of the cost-effectiveness of the prevention of disappearance of herd immunity.
A randomized study to assess the immunogenicity, antibody persistence and safety of a tetravalent meningococcal serogroups A, C, W-135 and Y tetanus toxoid conjugate vaccine in children aged 2–10 years
Vesikari, Timo; Forstén, Aino; Boutriau, Dominique; Bianco, Véronique; Van der Wielen, Marie; Miller, Jacqueline M.
Incidence of meningococcal diseases is high in children, and effective vaccines are needed for this age group. In this phase II, open, controlled study, 309 children aged 2–10 y from Finland were randomized (3:1) into two parallel groups to receive one dose of meningococcal ACWY-tetanus toxoid conjugate vaccine (ACWY-TT group; n = 231) or a licensed meningococcal ACWY polysaccharide vaccine (Men-PS group; n = 78). Serum bactericidal activity using rabbit complement (rSBA) was evaluated up to three years post-vaccination. Exploratory comparisons suggested that rSBA vaccine response rates and geometric mean titers (GMTs) for each serogroup at one month post-vaccination and rSBA GMTs for serogroups A, W-135 and Y up to three years post-vaccination were higher in the ACWY-TT compared with Men-PS group, but did not detect any difference between groups in terms of rSBA-MenC GMTs at three years post-vaccination; this is explained by the higher proportion of children from the Men-PS group who were excluded because they were re-vaccinated with a monovalent meningococcal serogroup C vaccine due to loss of protective antibody levels against this serogroup. Although there was a higher incidence of local reactogenicity in the ACWY-TT group, general and unsolicited symptoms reporting rates were comparable in both groups. This study showed that MenACWY-TT was immunogenic with a clinically acceptable safety profile in children aged 2–10 y. MenACWY-TT induced higher functional antibody titers for all serogroups, which persisted longer for serogroups A, W-135 and Y, than the MenACWY polysaccharide vaccine. This study has been registered at www.clinicaltrials.gov NCT00427908. PMID:23032168
Meningococcal polysaccharide A O-acetylation levels do not impact the immunogenicity of the quadrivalent meningococcal tetanus toxoid conjugate vaccine: results from a randomized, controlled phase III study of healthy adults aged 18 to 25 years.
Lupisan, Socorro; Limkittikul, Kriengsak; Sosa, Nestor; Chanthavanich, Pornthep; Bianco, Véronique; Baine, Yaela; Van der Wielen, Marie; Miller, Jacqueline M
In this study, we compared the immunogenicities of two lots of meningococcal ACWY-tetanus toxoid conjugate vaccine (MenACWY-TT) that differed in serogroup A polysaccharide (PS) O-acetylation levels and evaluated their immunogenicities and safety in comparison to a licensed ACWY polysaccharide vaccine (Men-PS). In this phase III, partially blinded, controlled study, 1,170 healthy subjects aged 18 to 25 years were randomized (1:1:1) to receive one dose of MenACWY-TT lot A (ACWY-A) (68% O-acetylation), MenACWY-TT lot B (ACWY-B) (92% O-acetylation), or Men-PS (82% O-acetylation). Immunogenicity was evaluated in terms of serum bactericidal activity using rabbit complement (i.e., rabbit serum bactericidal activity [rSBA]). Solicited symptoms, unsolicited adverse events (AEs), and serious AEs (SAEs) were recorded. The immunogenicities, in terms of rSBA geometric mean titers, were comparable for both lots of MenACWY-TT. The vaccine response rates across the serogroups were 79.1 to 97.0% in the two ACWY groups and 73.7 to 94.1% in the Men-PS group. All subjects achieved rSBA titers of ≥1:8 for all serogroups. All subjects in the two ACWY groups and 99.5 to 100% in the Men-PS group achieved rSBA titers of ≥1:128. Pain was the most common solicited local symptom and was reported more frequently in the ACWY group (53.9 to 54.7%) than in the Men-PS group (36.8%). The most common solicited general symptoms were fatigue and headache, which were reported by 28.6 to 30.3% and 26.9 to 31.0% of subjects, respectively. Two subjects reported SAEs; one SAE was considered to be related to vaccination (blighted ovum; ACWY-B group). The level of serogroup A PS O-acetylation did not affect vaccine immunogenicity. MenACWY-TT (lot A) was not inferior to Men-PS in terms of vaccine response and was well tolerated.
Pichichero, Michael E
The immunogenicity of polysaccharides as human vaccines was enhanced by coupling to protein carriers. Conjugation transformed the T cell-independent polysaccharide vaccines of the past to T cell-dependent antigenic vaccines that were much more immunogenic and launched a renaissance in vaccinology. This review discusses the conjugate vaccines for prevention of infections caused by Hemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis. Specifically, the characteristics of the proteins used in the construction of the vaccines including CRM, tetanus toxoid, diphtheria toxoid, Neisseria meningitidis outer membrane complex, and Hemophilus influenzae protein D are discussed. The studies that established differences among and key features of conjugate vaccines including immunologic memory induction, reduction of nasopharyngeal colonization and herd immunity, and antibody avidity and avidity maturation are presented. Studies of dose, schedule, response to boosters, of single protein carriers with single and multiple polysaccharides, of multiple protein carriers with multiple polysaccharides and conjugate vaccines administered concurrently with other vaccines are discussed along with undesirable consequences of conjugate vaccines. The clear benefits of conjugate vaccines in improving the protective responses of the immature immune systems of young infants and the senescent immune systems of the elderly have been made clear and opened the way to development of additional vaccines using this technology for future vaccine products. PMID:23955057
Black, Steven; Block, Stan L
Adolescents constitute a high-risk group for invasive meningococcal disease. MenACWY-CRM (Menveo, Novartis Vaccines, Cambridge, MA) is a quadrivalent meningococcal conjugate vaccine indicated to prevent invasive meningococcal disease caused by Neisseria meningitidis serogroups A, C, W-135, and Y. It has been approved for use in persons age 2-55 years. The tolerability and immunogenicity of MenACWY-CRM in adolescents have been ascertained in phase 2 and 3 trials against MPSV4 (Menomune, sanofi pasteur, Swiftwater, PA), an unconjugated quadrivalent meningococcal vaccine, and MenACWY-D (Menactra, sanofi pasteur), another conjugated quadrivalent meningococcal vaccine. Clinical trials also have demonstrated that MenACWY-CRM is well tolerated and immunogenic when administered to adolescents concomitantly with the combined tetanus, diphtheria, and acellular pertussis vaccine (Boostrix, GlaxoSmithKline Biologicals, Rixensart, Belgium) and the quadrivalent human papillomavirus vaccine (Gardasil, Merck & Co., Inc., Whitehouse Station, NJ). Copyright © 2013 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.
Bröker, Michael; Cooper, Brian; DeTora, Lisa M; Stoddard, Jeffrey J
Worldwide, invasive meningococcal disease affects about 500,000 people annually. Case fatality in developed countries averages 10%, and higher rates are reported in less prosperous regions. According to the World Health Organization, the most important pathogenic serogroups are A, B, C, W-135, X, and Y. Clinical features of invasive meningococcal disease make diagnosis and management difficult. Antibiotic measures are recommended for prophylaxis after exposure and for treatment of invasive meningococcal disease cases; however, resistant strains may be emerging. Vaccines are generally regarded as the best preventative measure for invasive meningococcal disease. Polysaccharide vaccines against serogroups A, C, W-135, and Y using protein conjugation technology have clear advantages over older plain polysaccharide formulations without a protein component. The first quadrivalent meningococcal conjugate vaccine (MenACWY-D) was licensed in the US in 2005. More recently, MenACWY-CRM (Menveo®) was licensed in Europe, the US, the Middle East, and Latin America. MenACWY-CRM uses cross-reactive material 197, a nontoxic mutant of diphtheria toxin, as the carrier protein. MenACWY-CRM offers robust immunogenicity in all age groups, with a tolerability profile similar to that of a plain polysaccharide vaccine. Given its potential for protecting persons from infancy to old age, MenACWY-CRM offers the opportunity to protect broad populations against invasive meningococcal disease. The most optimal strategy for use of the vaccine has to be assessed country by country on the basis of local epidemiology, individual health care systems, and need. PMID:21904459
Bröker, Michael; Cooper, Brian; Detora, Lisa M; Stoddard, Jeffrey J
Worldwide, invasive meningococcal disease affects about 500,000 people annually. Case fatality in developed countries averages 10%, and higher rates are reported in less prosperous regions. According to the World Health Organization, the most important pathogenic serogroups are A, B, C, W-135, X, and Y. Clinical features of invasive meningococcal disease make diagnosis and management difficult. Antibiotic measures are recommended for prophylaxis after exposure and for treatment of invasive meningococcal disease cases; however, resistant strains may be emerging. Vaccines are generally regarded as the best preventative measure for invasive meningococcal disease. Polysaccharide vaccines against serogroups A, C, W-135, and Y using protein conjugation technology have clear advantages over older plain polysaccharide formulations without a protein component. The first quadrivalent meningococcal conjugate vaccine (MenACWY-D) was licensed in the US in 2005. More recently, MenACWY-CRM (Menveo(®)) was licensed in Europe, the US, the Middle East, and Latin America. MenACWY-CRM uses cross-reactive material 197, a nontoxic mutant of diphtheria toxin, as the carrier protein. MenACWY-CRM offers robust immunogenicity in all age groups, with a tolerability profile similar to that of a plain polysaccharide vaccine. Given its potential for protecting persons from infancy to old age, MenACWY-CRM offers the opportunity to protect broad populations against invasive meningococcal disease. The most optimal strategy for use of the vaccine has to be assessed country by country on the basis of local epidemiology, individual health care systems, and need.
Full Text Available Michael Bröker, Brian Cooper, Lisa M DeTora, Jeffrey J StoddardGlobal Medical Affairs, Novartis Vaccines and Diagnostics, Marburg, Germany, and Cambridge, MA, USAAbstract: Worldwide, invasive meningococcal disease affects about 500,000 people annually. Case fatality in developed countries averages 10%, and higher rates are reported in less prosperous regions. According to the World Health Organization, the most important pathogenic serogroups are A, B, C, W-135, X, and Y. Clinical features of invasive meningococcal disease make diagnosis and management difficult. Antibiotic measures are recommended for prophylaxis after exposure and for treatment of invasive meningococcal disease cases; however, resistant strains may be emerging. Vaccines are generally regarded as the best preventative measure for invasive meningococcal disease. Polysaccharide vaccines against serogroups A, C, W-135, and Y using protein conjugation technology have clear advantages over older plain polysaccharide formulations without a protein component. The first quadrivalent meningococcal conjugate vaccine (MenACWY-D was licensed in the US in 2005. More recently, MenACWY-CRM (Menveo® was licensed in Europe, the US, the Middle East, and Latin America. MenACWY-CRM uses cross-reactive material 197, a nontoxic mutant of diphtheria toxin, as the carrier protein. MenACWY-CRM offers robust immunogenicity in all age groups, with a tolerability profile similar to that of a plain polysaccharide vaccine. Given its potential for protecting persons from infancy to old age, MenACWY-CRM offers the opportunity to protect broad populations against invasive meningococcal disease. The most optimal strategy for use of the vaccine has to be assessed country by country on the basis of local epidemiology, individual health care systems, and need.Keywords: invasive meningococcal disease, quadrivalent meningococcal conjugate vaccine, Neisseria meningitidis
Klein, Nicola P; Reisinger, Keith S; Johnston, William; Odrljin, Tatjana; Gill, Christopher J; Bedell, Lisa; Dull, Peter
In phase II studies, MenACWY-CRM elicited robust immunologic responses in young infants. We now present results from our pivotal phase III infant immunogenicity/safety study. In this open-label phase III study, we randomized full-term 2-month-old infants to 4 doses of MenACWY-CRM coadministered with routine vaccines at 2, 4, 6, and 12 months of age or with routine vaccines alone. We monitored for local and systemic reactions and serious adverse events among all study participants and evaluated for sufficiency of the immune responses to MenACWY-CRM through serum bactericidal activity assay with human complement. Bactericidal antibodies were present in 94% to 100% of subjects against each of the serogroups in MenACWY-CRM after the 4-dose series and were 67% to 97% after the first 3 doses. Geometric mean titers were higher after the fourth dose of MenACWY-CRM compared with a single dose of MenACWY-CRM at 12 months of age for all serogroups (range of ratios, 4.5-38). Responses to 3 doses of routine vaccines coadministered with MenACWY-CRM were noninferior to routine vaccinations alone, except for small differences in pneumococcal serotype 6B responses after dose 3 but not dose 4 and pertactin after dose 3. Inclusion of MenACWY-CRM did not affect the safety or reactogenicity profiles of the routine infant vaccine series. A 4-dose series of MenACWY-CRM was highly immunogenic and well tolerated in young infants, and it can be coadministered with routine infant vaccines. Substantial immunity was conferred after the first 3 doses administered at 2, 4, and 6 months of age.
The impact of administration of conjugate vaccines containing cross reacting material on Haemophilus influenzae type b antibody responses in infants: A systematic review and meta-analysis of randomised controlled trials.
Voysey, Merryn; Sadarangani, Manish; Clutterbuck, Elizabeth; Bolgiano, Barbara; Pollard, Andrew J
Protein-polysaccharide conjugate vaccines such as Haemophilus influenzae type b (Hib), meningococcal, and pneumococcal vaccine, induce immunological memory and longer lasting protection than plain polysaccharide vaccines. The most common proteins used as carriers are tetanus toxoid (TT) and cross reacting material-197 (CRM), a mutant form of diphtheria toxoid. CRM conjugate vaccines have been reported to suppress antibody responses to co-administered Hib-TT vaccine. We conducted a systematic review and meta-analysis of randomised controlled trials in which infants were randomised to receive meningococcal or pneumococcal conjugate vaccines along with Hib-TT. Trials of licensed vaccines with different carrier proteins were included for group C meningococcal (MenC), quadrivalent ACWY meningococcal (MenACWY), and pneumococcal vaccines. Twenty-three trials were included in the meta-analyses. Overall, administration of MenC-CRM in a 2 or 3 dose schedule resulted in a 45% reduction in Hib antibody concentrations (GMR 0.55, 95% CI 0.49-0.62). MenACWY-CRM boosted Hib antibody responses by 22% (GMR 1.22, 95% CI 1.06-1.41) whilst pneumococcal CRM conjugate vaccines had no impact on Hib antibody responses (GMR 0.91, 95% CI 0.68-1.22). The effect of CRM protein-polysaccharide conjugate vaccines on Hib antibody responses varies greatly between vaccines. Co-administration of a CRM conjugate vaccine can produce either positive or negative effects on Hib antibody responses. These inconsistencies suggest that CRM itself may not be the main driver of variability in Hib responses, and challenge current perspectives on this issue. Copyright © 2016 Elsevier Ltd. All rights reserved.
Baxter, Roger; Keshavan, Pavitra; Welsch, Jo Anne; Han, Linda; Smolenov, Igor
Persistence of bactericidal antibodies following vaccination is extremely important for protection against invasive meningococcal disease, given the epidemiology and rapid progression of meningococcal infection. We present an analysis of antibody persistence and booster response to MenACWY-CRM, in adolescents, children and infants, from 7 clinical studies. Immunogenicity was assessed using the serum bactericidal assay with both human and rabbit complement. Post-vaccination hSBA titers were high, with an age- and serogroup-specific decline in titers up to 1 y and stable levels up to 5 y The waning of hSBA titers over time was more pronounced among infants and toddlers and the greatest for serogroup A. However, rSBA titers against serogroup A were consistently higher and showed little decline over time, suggesting that protection against this serogroup may be sustained. A single booster dose of MenACWY-CRM administered at 3 to 5 y induced a robust immune response in all age groups.
Hirve, Siddhivinayak; Bavdekar, Ashish; Pandit, Anand; Juvekar, Sanjay; Patil, Malini; Preziosi, Marie-Pierre; Tang, Yuxiao; Marchetti, Elisa; Martellet, Lionel; Findlow, Helen; Elie, Cheryl; Parulekar, Varsha; Plikaytis, Brian; Borrow, Ray; Carlone, George; Kulkarni, Prasad S; Goel, Akshay; Suresh, Karupothula; Beri, Suresh; Kapre, Subhash; Jadhav, Suresh; Preaud, Jean-Marie; Viviani, Simonetta; LaForce, F Marc
This study compares the immunogenicity and safety of a single dose of a new meningococcal A conjugate vaccine (PsA-TT, MenAfriVac™, Serum Institute of India Ltd., Pune) against the meningococcal group A component of a licensed quadrivalent meningococcal polysaccharide vaccine (PsACWY, Mencevax ACWY(®), GSK, Belgium) 28 days after vaccination in Indian children. This double-blind, randomized, controlled study included 340 Indian children aged 2-10 years enrolled from August to October 2007; 169 children received a dose of PsA-TT while 171 children received a dose of PsACWY. Intention-to-treat analysis showed that 95.2% of children in PsA-TT group had a ≥4-fold response in serum bactericidal titers (rSBA) 28 days post vaccination as compared to 78.2% in the PsACWY group. A significantly higher rSBA GMT (11,209, 95%CI 9708-12,942) was noted in the PsA-TT group when compared to PsACWY group (2838, 95%CI 2368-3401). Almost all children in both vaccine groups had a ≥4-fold response in group A-specific IgG concentration but the IgG GMC was significantly greater in the PsA-TT group (89.1 μg/ml, 95%CI 75.5-105.0) when compared to the PsACWY group (15.3 μg/ml, 95%CI 12.3-19.2). Local and systemic reactions during the 4 days after immunization were similar for both vaccine groups except for tenderness (30.2% in PsA-TT group vs 12.3% in PsACWY group). None of the adverse events or serious adverse events was related to the study vaccines. We conclude that MenAfriVac™ is well tolerated and significantly more immunogenic when compared to a licensed polysaccharide vaccine, in 2-to-10-year-old Indian children. Copyright © 2012 Elsevier Ltd. All rights reserved.
... for example, lack of a functioning spleen, need vac- influenzae type b) cination with Hib. Talk to ... of developing severe complications because of your HIV infection. Meningococcal ACWY (Men- ACWY, MCV4) Yes! MenACWY vaccine ...
Seroprevalence and placental transmission of maternal antibodies specific for Neisseria meningitidis Serogroups A, C, Y and W135 and influence of maternal antibodies on the immune response to a primary course of MenACWY-CRM vaccine in the United Kingdom.
Blanchard-Rohner, Geraldine; Snape, Matthew D; Kelly, Dominic F; O'Connor, Daniel; John, Tessa; Kibwana, Elizabeth; Parks, Hannah; Ford, Karen; Dull, Peter M; Pollard, Andrew J
Maternal antibodies give neonates some protection against bacterial infection. We measured antibodies against Neisseria meningitidis serogroups A, C, Y and W135 in mothers and their 2-month-old infants at study enrollment. We also assessed the impact of maternal antibody present at 2 months of age on the immune response to a primary course of quadrivalent meningococcal conjugate vaccine (MenACWY-CRM197) given at 2 and 4 months of age. This was a single-center, open-label, randomized study undertaken in Oxford, United Kingdom. Two hundred sixteen healthy infants were enrolled in the study and vaccinated with MenACWY-CRM197 at 2 and 4 months of age. Blood was obtained from all mothers, in a subset of infants at 2 months and all infants at 5 months. Antibody and memory B-cell responses at 5 months were correlated with maternal antibodies. Mothers had low IgG antibodies against serogroups C, W135 and Y polysaccharides, but high serogroup A antibody, whereas 61-78% had protective human complement serum bactericidal activity (hSBA) (≥1:4) for serogroups C, W135 and Y but only 31% for serogroup A. Only 9%, 32%, 45% and 19% of 2-month-old infants had hSBA ≥1:4 for serogroups A, C, W135 and Y, respectively. Maternal antibody had little association on responses to MenACWY-CRM197, except a moderate negative association between MenC-specific bactericidal antibody at 2 and 5 months (r = -0.5, P = 0.006, n = 28) and between carrier-specific IgG antibody at 2 months and MenC-specific hSBA/IgG antibody at 5 months (r = -0.4, P = 0.02 and 0.04, n = 32 and 23). Nonetheless, 90% of infants achieved protective MenC-hSBA titers after vaccination at 2 and 4 months of age. The levels of serogroup-specific meningococcal antibodies were low in mothers and 2-month-old infants. Immunizing mothers before or during pregnancy with meningococcal conjugate vaccines might increase antibody levels in early infancy and provide protection against infection due to N. meningitidis.
... Español Text Size Email Print Share Meningococcal ACWY Vaccines: What You Need to Know (VIS) Page Content ... to help protect against serogroup B . Meningococcal ACWY Vaccines There are two kinds of meningococcal vaccines licensed ...
Bröker, Michael; Berti, Francesco; Costantino, Paolo
ABSTRACT Various glycoprotein conjugate vaccines have been developed for the prevention of invasive meningococcal disease, having significant advantages over pure polysaccharide vaccines. One of the most important features of the conjugate vaccines is the induction of a T-cell dependent immune response, which enables both the induction of immune memory and a booster response after repeated immunization. The nature of the carrier protein to which the polysaccharides are chemically linked, is often regarded as the main component of the vaccine in determining its immunogenicity. However, other factors can have a significant impact on the vaccine's profile. In this review, we explore the physico-chemical properties of meningococcal conjugate vaccines, which can significantly contribute to the vaccine's immunogenicity. We demonstrate that the carrier is not the sole determining factor of the vaccine's profile, but, moreover, that the conjugate vaccine's immunogenicity is the result of multiple physico-chemical structures and characteristics. PMID:26934310
Pichichero, Michael E
The immunogenicity of polysaccharides as human vaccines was enhanced by coupling to protein carriers. Conjugation transformed the T cell-independent polysaccharide vaccines of the past to T cell-dependent antigenic vaccines that were much more immunogenic and launched a renaissance in vaccinology. This review discusses the conjugate vaccines for prevention of infections caused by Hemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis. Specifically, the characteristics of the proteins used in the construction of the vaccines including CRM, tetanus toxoid, diphtheria toxoid, Neisseria meningitidis outer membrane complex, and Hemophilus influenzae protein D are discussed. The studies that established differences among and key features of conjugate vaccines including immunologic memory induction, reduction of nasopharyngeal colonization and herd immunity, and antibody avidity and avidity maturation are presented. Studies of dose, schedule, response to boosters, of single protein carriers with single and multiple polysaccharides, of multiple protein carriers with multiple polysaccharides and conjugate vaccines administered concurrently with other vaccines are discussed along with undesirable consequences of conjugate vaccines. The clear benefits of conjugate vaccines in improving the protective responses of the immature immune systems of young infants and the senescent immune systems of the elderly have been made clear and opened the way to development of additional vaccines using this technology for future vaccine products.
Cristina Aparecida Borges Laval
Full Text Available Acute bacterial meningitis is an important cause of morbidity and mortality among children less than five years old. Haemophilus influenzae, Streptococcus pneumoniae and Neisseria meningitidis are the most important agents of bacterial meningitis in developing countries. The development of the conjugate vaccines in the beginning of the 90's, especially type b H. influenzae (Hib, and more recently the heptavalent pneumococcal and the serogroup C meningococcal vaccines, have contributed directly to changes in the epidemiological profile of these invasive diseases (direct effect and of their carriage status (indirect effect. We review the impact of the Hib conjugate vaccine in Latin American countries, where this vaccine has been implemented, and the potential of pneumococcal and meningococcal conjugate vaccines for the reduction of meningitis worldwide. We also address constraints for the development and delivery of these vaccines and review new candidate state-of-the-art vaccines. The greatest challenge, undoubtedly, is to implement these vaccines worldwide, especially in the developing regions.
Holme, Daniel; Findlow, Helen; Sow, Samba O.; Idoko, Olubukola T.; Preziosi, Marie-Pierre; Carlone, George; Plikaytis, Brian D.; Borrow, Ray
Background. A group A meningococcal conjugate vaccine, PsA-TT, was licensed in 2010 and was previously studied in a phase 2 clinical trial to evaluate its safety and immunogenicity in African children 12–23 months of age. Methods. Subjects received either PsA-TT; meningococcal group A, C, W, Y polysaccharide vaccine (PsACWY); or Haemophilus influenzae type b conjugate vaccine (Hib-TT). Forty weeks following primary vaccination, the 3 groups were further randomized to receive either PsA-TT, one-fifth dose of PsACWY, or Hib-TT. Group A–specific immunoglobulin G (IgG) subclass response was characterized using an enzyme-linked immunosorbent assay. Results. The predominant IgG subclass response, regardless of vaccine, was IgG1. One month following primary vaccination, the geometric mean concentrations (GMCs) of IgG1 and IgG2 in the PsA-TT group were 21.73 µg/mL and 6.27 µg/mL, whereas in the PsACWY group the mean GMCs were 2.01 µg/mL and 0.97 µg/mL, respectively (P Group A–specific IgG1 and IgG2 GMCs remained greater in the PsA-TT group than in the PsACWY group 40 weeks following primary vaccination (P vaccines. Conclusions. Vaccination of African children aged 12–24 months with either PsA-TT or PsACWY elicited a predominantly IgG1 response. The IgG1:IgG2 mean ratio decreased following successive vaccination with PsACWY, indicating a shift toward IgG2, suggestive of the T-cell–independent immune response commonly associated with polysaccharide antigens. Clinical Trials Registration. SRCTN78147026. PMID:26553689
Full Text Available Despite good cover with 7-valent vaccination, invasive pneumococcal infections may still be misdiagnosed and may lead to lifethreatening situations or death in young children. New serotypes are emerging and, therefore, clinicians must keep a high level of suspicion in young children regardless of their vaccination status. We report three cases of invasive pneumococcal infection due to new serotypes not covered by the 7-valent conjugated vaccine, two of which led children to death.
Nurhonen, Markku; Auranen, Kari
Pneumococcal conjugate vaccination has proved highly effective in eliminating vaccine-type pneumococcal carriage and disease. However, the potential adverse effects of serotype replacement remain a major concern when implementing routine childhood pneumococcal conjugate vaccination programmes. Applying a concise predictive model, we present a ready-to-use quantitative tool to investigate the implications of serotype replacement on the net effectiveness of vaccination against invasive pneumococcal disease (IPD) and to guide in the selection of optimal vaccine serotype compositions. We utilise pre-vaccination data on pneumococcal carriage and IPD and assume partial or complete elimination of vaccine-type carriage, its replacement by non-vaccine-type carriage, and stable case-to-carrier ratios (probability of IPD per carriage episode). The model predicts that the post-vaccination IPD incidences in Finland for currently available vaccine serotype compositions can eventually decrease among the target age group of children replacement through herd effects, the decrease among the older population is predicted to be much less (20-40%). We introduce a sequential algorithm for the search of optimal serotype compositions and assess the robustness of inferences to uncertainties in data and assumptions about carriage and IPD. The optimal serotype composition depends on the age group of interest and some serotypes may be highly beneficial vaccine types in one age category (e.g. 6B in children), while being disadvantageous in another. The net effectiveness will be improved only if the added serotype has a higher case-to-carrier ratio than the average case-to-carrier ratio of the current non-vaccine types and the degree of improvement in effectiveness depends on the carriage incidence of the serotype. The serotype compositions of currently available pneumococcal vaccines are not optimal and the effectiveness of vaccination in the population at large could be improved by including
Breukels, M. A.; Spanjaard, L.; Sanders, L. A.; Rijkers, G. T.
Infant vaccination with conjugated Haemophilus influenzae type b (Hib) vaccine is highly effective in protecting against invasive Hib infections, but vaccine failures do occur. Twenty-one vaccine failures are reported since the introduction of the Hib conjugate vaccine in The Netherlands. Of the 14
Echániz-Avilés Irma Gabriela
Full Text Available Streptococcus pneumoniae is one of the leading causes of both invasive and noninvasive diseases in the pediatric population and continues to represent a significant public health burden worldwide. The increasing incidence of antibioticresistant strains of the pathogen has complicated treatment and management of the various pneumococcal disease manifestations. Thus, the best management strategy may be the prevention of pneumococcal diseases through vaccination. Although several pneumococcal conjugate vaccines have been clinically studied in infants and children, only a 7-valent conjugate vaccine (PNCRM7; Prevnar®/Prevenar® is currently approved for the prevention of invasive disease. Vaccination with PNCRM7 is safe and effective in infants and young children. Routine vaccination with the conjugate vaccine could improve outcomes by safeguarding against the development of antibiotic-resistant strains of S. pneumoniae, thus simplifying the management of pneumococcal disease. Additionally, the overall costs associated with the treatment of pneumococcal diseases could be substantially reduced, particularly in developing countries. The time has come for fully applying this new advancement against S. pneumoniae, to benefit the children of the world. The Spanish version of this paper is available at: http://www.insp.mx/salud/index.html
Safety and Immunogenicity of Coadministering a Combined Meningococcal Serogroup C and Haemophilus influenzae Type b Conjugate Vaccine with 7-Valent Pneumococcal Conjugate Vaccine and Measles, Mumps, and Rubella Vaccine at 12 Months of Age ▿
Miller, Elizabeth; Andrews, Nick; Waight, Pauline; Findlow, Helen; Ashton, Lindsey; England, Anna; Stanford, Elaine; Matheson, Mary; Southern, Joanna; Sheasby, Elizabeth; Goldblatt, David; Borrow, Ray
The coadministration of the combined meningococcal serogroup C conjugate (MCC)/Haemophilus influenzae type b (Hib) vaccine with pneumococcal conjugate vaccine (PCV7) and measles, mumps, and rubella (MMR) vaccine at 12 months of age was investigated to assess the safety and immunogenicity of this regimen compared with separate administration of the conjugate vaccines. Children were randomized to receive MCC/Hib vaccine alone followed 1 month later by PCV7 with MMR vaccine or to receive all thr...
Welte, R.; Trotter, C.L.; Edmunds, W.J.; Postma, Maarten; Beutels, P.H.
In recent years, several countries have experienced increases in the incidence of serogroup C meningococcal disease. It can be controlled with older polysaccharide vaccines and particularly the recently developed conjugate vaccines. For 21 developed countries, we investigated the role that economic
Immunisation has contributed greatly to the control of vaccine-preventable diseases and therefore to improvements in health and survival, especially among young children, and remains one of the most successful and cost-effective public health interventions. This remains true for many of the newer, more expensive ...
Gill, Christopher J; Baxter, Roger; Anemona, Alessandra; Ciavarro, Giuseppe; Dull, Peter
The persistence of human bactericidal activity (hSBA) responses in adolescents was assessed 22 months after vaccination with one dose of Menveo® (MenACWY-CRM; Novartis) or Menactra® (MCV4) (sanofi pasteur). The proportion of subjects with hSBA titers ≥8 was significantly higher among recipients of MenACWY-CRM than MCV4 for serogroups A, W-135 and Y.
S. V. Il'ina
Full Text Available Study aim: analyzing the results of pneumococcal infection vaccination conducted to reduce infantile morbidity and mortality in 2011-2012 at the expenses of the Irkutsk municipal budget. Patients and methods. Vaccination using the 7- and 13-valent pneumococcal conjugated vaccine was conducted for more than 700 risk group children: premature infants, children with congenital heart diseases or bronchopulmonary dysplasia from 2 months to 2 years of age. 193 vaccinated children had been observed for 1.5 years. 30% of premature infants and 46% of children with congenital heart diseases were vaccinated using the PCV7/PCV13 vaccine at the age of 2-6 months, 52 and 40% - at the age of 7-11 months, accordingly. The PCV7/PCV13 vaccine was administered together with other vaccines of the national preventive vaccination calendar in 65% of cases. Results. Rate of general post-vaccinal reactions (body temperature increase from 37.6 to 38.0oC – 4%; no local reactions were registered. No other unfavorable phenomena were noted in the post-vaccinal period. No cases of pneumonia, meningitis, acute otitis media and bronchoobstructive syndrome were registered within the observation period. Conclusions: pneumococcal infection vaccination of premature infants with congenital heart diseases and bronchopulmonary dysplasia conducted in Irkutsk proved high efficacy and safety of the used vaccine – PCV7/PCV13.
Anderson, E L; Bowers, T; Mink, C M; Kennedy, D J; Belshe, R B; Harakeh, H; Pais, L; Holder, P; Carlone, G M
A meningococcal vaccine containing group A and C polysaccharides conjugated to CRM197 was evaluated in 50 adults. Vaccinees were entered into one of five groups: 30 adults received a single dose of either 22, 11, or 5.5 micrograms of the conjugated A-C vaccine; 10 received an approved meningococcal vaccine; and 10 received saline injections. Local and systemic reactions to vaccines were recorded, and immune responses were determined. The experimental meningococcal vaccine was well tolerated, ...
Dorell, Christina; Yankey, David; Kennedy, Allison; Stokley, Shannon
We aim to describe factors that influence parental decisions to vaccinate their adolescents. Data from the July to December 2010 National Immunization Survey-Teen Parental Concerns Module were analyzed to determine factors that influence parental decisions to vaccinate their adolescents. Parents reported that their adolescent's health care provider recommended tetanus toxoid/tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Td/Tdap; 74.4%), meningococcal conjugate (MenACWY; 60.3%), and human papillomavirus (HPV; 71.3%). Vaccination coverage estimates were significantly higher among parents who reported receiving a provider recommendation: 85.2% versus 76.7% (Td/Tdap), 77.3% versus 49.7% (MenACWY), and 62.2% versus 21.5% (HPV). Compared with Td/Tdap and MenACWY, fewer HPV vaccination conversations included recommendations for vaccination. Other than health care providers, school requirements (46.1%), news coverage (31.2%), and family (31.0%) were most frequently reported influences on parental vaccination decisions. Many factors influence parental decisions to vaccinate their adolescents; one of the most important factors is the provider recommendation. Missed opportunities for vaccination persist when strong vaccination recommendations are not given or are delayed.
Xin, Hong; Cartmell, Jonathan; Bailey, Justin J.; Dziadek, Sebastian; Bundle, David R.; Cutler, Jim E.
Our research on pathogenesis of disseminated candidiasis led to the discovery that antibodies specific for Candida albicans cell surface β-1, 2–mannotriose [β-(Man)3] protect mice. A 14 mer peptide Fba, which derived from the N-terminal portion of the C. albicans cytosolic/cell surface protein fructose-bisphosphate aldolase, was used as the glycan carrier and resulted in a novel synthetic glycopeptide vaccine β-(Man)3-Fba. By a dendritic cell-based immunization approach, this conjugate induced protective antibody responses against both the glycan and peptide parts of the vaccine. In this report, we modified the β-(Man)3-Fba conjugate by coupling it to tetanus toxoid (TT) in order to improve immunogenicity and allow for use of an adjuvant suitable for human use. By new immunization procedures entirely compatible with human use, the modified β-(Man)3-Fba-TT was administered either alone or as a mixture made with alum or monophosphoryl lipid A (MPL) adjuvants and given to mice by a subcutaneous (s.c.) route. Mice vaccinated with or, surprisingly, without adjuvant responded well by making robust antibody responses. The immunized groups showed a high degree of protection against a lethal challenge with C. albicans as evidenced by increased survival times and reduced kidney fungal burden as compared to control groups that received only adjuvant or DPBS buffer prior to challenge. To confirm that induced antibodies were protective, sera from mice immunized against the β-(Man)3-Fba-TT conjugate transferred protection against disseminated candidiasis to naïve mice, whereas C. albicans-absorbed immune sera did not. Similar antibody responses and protection induced by the β-(Man)3-Fba-TT vaccine was observed in inbred BALB/c and outbred Swiss Webster mice. We conclude that addition of TT to the glycopeptide conjugate results in a self-adjuvanting vaccine that promotes robust antibody responses without the need for additional adjuvant, which is novel and represents a
Hamidi, Ahd; Verdijk, Pauline; Kreeftenberg, Hans
Introduction of Haemophilus influenzae type b (Hib) vaccine in low- and middle-income countries has been limited by cost and availability of Hib conjugate vaccines for a long time. It was previously recognized by the Institute for Translational Vaccinology (Intravacc, originating from the former Vaccinology Unit of the National Institute of Public Health [RIVM] and the Netherlands Vaccine Institute [NVI]) that local production of a Hib conjugate vaccine would increase the affordability and sustainability of the vaccine and thereby help to speed up Hib introduction in these countries. A new affordable and a non-infringing production process for a Hib conjugate vaccine was developed, including relevant quality control tests, and the technology was transferred to a number of vaccine manufacturers in India, Indonesia, and China. As part of the Hib technology transfer project managed by Intravacc, a preclinical toxicity study was conducted in the Netherlands to test the safety and immunogenicity of this new Hib conjugate vaccine. The data generated by this study were used by the technology transfer partners to accelerate the clinical development of the new Hib conjugate vaccine. A repeated dose toxicity and local tolerance study in rats was performed to assess the reactogenicity and immunogenicity of a new Hib conjugate vaccine compared to a licensed vaccine. The results showed that the vaccine was well tolerated and immunogenic in rats, no major differences in both safety and immunogenicity in rats were found between the vaccine produced according to the production process developed by Intravacc and the licensed one. Rats may be useful to verify the immunogenicity of Hib conjugate vaccines and for preclinical evaluation. In general, nonclinical evaluation of the new Hib conjugate vaccine, including this proof of concept (safety and immunogenicity study in rats), made it possible for technology transfer partners, having implemented the original process with no changes
Vučina, V Višekruna; Filipović, S Kurečić; Kožnjak, N; Stamenić, V; Clark, A D; Mounaud, B; Blau, J; Hoestlandt, C; Kaić, B
Pneumococcus is a known cause of meningitis, pneumonia, sepsis, and acute otitis media in children and adults globally. Two new vaccines for children have the potential to prevent illness, disability, and death, but these vaccines are expensive. The Croatian Ministry of Health has considered introducing the vaccine in the past, but requires economic evidence to ensure that the limited funds available for health care will be used in the most effective way. Croatia appointed a multidisciplinary team of experts to evaluate the cost-effectiveness of introducing pneumococcal conjugate vaccination (PCV) into the national routine child immunization program. Both 10-valent and 13-valent PCV (PCV10 and PCV13) were compared to a scenario assuming no vaccination. The TRIVAC decision-support model was used to estimate cost-effectiveness over the period 2014-2033. We used national evidence on demographics, pneumococcal disease incidence and mortality, the age distribution of disease in children, health service utilization, vaccine coverage, vaccine timeliness, and serotype coverage. Vaccine effectiveness was based on evidence from the scientific literature. Detailed health care costs were not available from the Croatian Institute for Health Insurance at the time of the analysis so assumptions and World Health Organization (WHO) estimates for Croatia were used. We assumed a three-dose primary vaccination schedule, and an initial price of US$ 30 per dose for PCV10 and US$ 35 per dose for PCV13. We ran univariate sensitivity analyses and multivariate scenario analyses. Either vaccine is estimated to prevent approximately 100 hospital admissions and one death each year in children younger than five in Croatia. Compared to no vaccine, the discounted cost-effectiveness of either vaccine is estimated to be around US$ 69,000-77,000 per disability-adjusted life-years (DALYs) averted over the period 2014-2033 (from the government or societal perspective). Only two alternative scenarios
Kim, Sun-Young; Lee, Gene; Goldie, Sue J
Gambia is the second GAVI support-eligible country to introduce the 7-valent pneumococcal conjugate vaccine (PCV7), but a country-specific cost-effectiveness analysis of the vaccine is not available. Our objective was to assess the potential impact of PCVs of different valences in The Gambia. We synthesized the best available epidemiological and cost data using a state-transition model to simulate the natural histories of various pneumococcal diseases. For the base-case, we estimated incremental cost (in 2005 US dollars) per disability-adjusted life year (DALY) averted under routine vaccination using PCV9 compared to no vaccination. We extended the base-case results for PCV9 to estimate the cost-effectiveness of PCV7, PCV10, and PCV13, each compared to no vaccination. To explore parameter uncertainty, we performed both deterministic and probabilistic sensitivity analyses. We also explored the impact of vaccine efficacy waning, herd immunity, and serotype replacement, as a part of the uncertainty analyses, by assuming alternative scenarios and extrapolating empirical results from different settings. Assuming 90% coverage, a program using a 9-valent PCV (PCV9) would prevent approximately 630 hospitalizations, 40 deaths, and 1000 DALYs, over the first 5 years of life of a birth cohort. Under base-case assumptions ($3.5 per vaccine), compared to no intervention, a PCV9 vaccination program would cost $670 per DALY averted in The Gambia. The corresponding values for PCV7, PCV10, and PCV13 were $910, $670, and $570 per DALY averted, respectively. Sensitivity analyses that explored the implications of the uncertain key parameters showed that model outcomes were most sensitive to vaccine price per dose, discount rate, case-fatality rate of primary endpoint pneumonia, and vaccine efficacy against primary endpoint pneumonia. Based on the information available now, infant PCV vaccination would be expected to reduce pneumococcal diseases caused by S. pneumoniae in The Gambia
Full Text Available Abstract Background Gambia is the second GAVI support-eligible country to introduce the 7-valent pneumococcal conjugate vaccine (PCV7, but a country-specific cost-effectiveness analysis of the vaccine is not available. Our objective was to assess the potential impact of PCVs of different valences in The Gambia. Methods We synthesized the best available epidemiological and cost data using a state-transition model to simulate the natural histories of various pneumococcal diseases. For the base-case, we estimated incremental cost (in 2005 US dollars per disability-adjusted life year (DALY averted under routine vaccination using PCV9 compared to no vaccination. We extended the base-case results for PCV9 to estimate the cost-effectiveness of PCV7, PCV10, and PCV13, each compared to no vaccination. To explore parameter uncertainty, we performed both deterministic and probabilistic sensitivity analyses. We also explored the impact of vaccine efficacy waning, herd immunity, and serotype replacement, as a part of the uncertainty analyses, by assuming alternative scenarios and extrapolating empirical results from different settings. Results Assuming 90% coverage, a program using a 9-valent PCV (PCV9 would prevent approximately 630 hospitalizations, 40 deaths, and 1000 DALYs, over the first 5 years of life of a birth cohort. Under base-case assumptions ($3.5 per vaccine, compared to no intervention, a PCV9 vaccination program would cost $670 per DALY averted in The Gambia. The corresponding values for PCV7, PCV10, and PCV13 were $910, $670, and $570 per DALY averted, respectively. Sensitivity analyses that explored the implications of the uncertain key parameters showed that model outcomes were most sensitive to vaccine price per dose, discount rate, case-fatality rate of primary endpoint pneumonia, and vaccine efficacy against primary endpoint pneumonia. Conclusions Based on the information available now, infant PCV vaccination would be expected to reduce
Harboe, Zitta B; Valentiner-Branth, Palle; Ingels, Helene
A seven-valent pneumococcal conjugate vaccine (PCV7) was introduced in the Danish childhood immunization program (2+1 schedule) in October 2007, followed by PCV13 starting from April 2010. The nationwide incidence of IPD among children younger than 5 years nearly halved after the introduction...... of children suspected to present with a vaccine failure. The period between April 19 and December 31, 2010 was considered a PCV7/PCV13 transitional period, where both vaccines were offered. We identified 45 episodes of IPD caused by a PCV7 serotype (23% of the total number) and 105 (55%) caused by one...... of the 6 additional serotypes in PCV13. Ten children had received at least one PCV7 dose before the onset of IPD caused by a PCV7 serotype. Seven children were considered to be incompletely vaccinated before IPD, but only three cases fulfilled the criteria of vaccine failure (caused by serotypes 14, 19F...
Full Text Available Invasive pneumococcal infection is the most frequent cause of death in patients with immunodeficiences. The antibiotics used previously for prevention purposes are not efficient enough due to the developing antibiotic resistance. Polysaccharide pneumococcal vaccines create short-lived immunity. The overview summarizes the experience of applying conjugated pneumococcal vaccines in patients with primary immunodeficiences, HIV infection, oncological and rheumatic diseases. Key words: pneumococcal infection, pneumococcal conjugated vaccines, children, immunosuppression. (Pediatric Pharmacology. – 2010; 7(5:18-23
Kuhlmann, Alexander; von der Schulenburg, J-Matthias Graf
In 2009, the European Medicines Agency granted approval for two higher-valent pneumococcal conjugate vaccines. This study aims to evaluate the cost-effectiveness of universal infant (historical vaccination scheme in infants as well as indirect herd effects and replacement disease. We used German epidemiological data to calculate episodes of IPD, PNE, and AOM, as well as direct and indirect effects of the vaccination. Parameter uncertainty was tested in univariate and probabilistic sensitivity analyses. In the base-case analysis, the ICER of PCV13 versus PCV10 infant vaccination was EUR 9826 per quality-adjusted life-year (QALY) gained or EUR 5490 per life-year (LY) gained from the societal perspective and EUR 3368 per QALY gained or EUR 1882 per LY gained from the perspective of the German statutory health insurance. The results were particularly sensitive to the magnitude of indirect effects of both vaccines. Universal infant vaccination with PCV13 is likely to be a cost-effective intervention compared with PCV10 within the German health care system, if additional net indirect effects of PCV13 vaccination are significant.
Full Text Available An experience of immunization with pneumococcal conjugated 7-valent vaccine Prevenar in 234 children under 5 years old with different state of health was analyzed. There were no any severe reactions, postvaccinal complications or local reactions to the vaccine injection. Mild and moderate postvaccinal reactions were detected in 3,4% (n = 8 of children. The vaccine can be used in children under 5 years old.Key words: children, vaccination, pneumococcal conjugated 7-valent vaccine, safety.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2010;9(2:119-123
van Gils, E.J.M.; Hak, E.; Veenhoven, R.H.; Rodenburg, G.D.; Bogaert, D.; Bruin, J.P.; van Alphen, L.
Background: Heptavalent pneumococcal conjugate vaccine (PCV7) shifts nasopharyngeal colonisation with vaccine serotype pneumococci towards nonvaccine serotypes. Because of the reported negative association of vaccine serotype pneumococci and Staphylococcus aureus in the nasopharynx, we explored the
Full Text Available World Health Organization has recommended all countries to introduction of Pneumococcal Conjugate Vaccine (PCV in routine immunization schedule, especially those countries with higher rate of mortality in children. However, Islamic Republic of Iran and more than 50 other countries including Algeria, Antigua and Barbuda, Belarus, Belize, Bhutan, Bosnia and Herzegovina, Brunei Darussalam, Cabo Verde, Chad, China, Comoros, Cook Islands, Croatia, Cuba, Czech Republic, Democratic People's Republic of Korea, Dominica, Egypt, Equatorial Guinea, Estonia, Gabon, Grenada, Guinea, Haiti, India, Jamaica, Jordan, Malaysia, Maldives, Malta, Montenegro, Nauru, Poland, Romania, Saint Kitts and Nevis, Saint Lucia, Saint Vincent and the Grenadines, Samoa, San Marino, Serbia, Seychelles, Slovenia, Somalia, South Sudan, Sri Lanka, Syrian Arab Republic, Tajikistan, Thailand, The former Yugoslav Republic of Macedonia, Timor-Leste, Tonga, Tunisia, Turkmenistan, Tuvalu, Ukraine, Vanuatu, and Viet Namhave not introduced PCV till April 2016.
Leach, Amanda Jane; Wigger, Christine; Andrews, Ross; Chatfield, Mark; Smith-Vaughan, Heidi; Morris, Peter Stanley
In 2001 when 7-valent pneumococcal conjugate vaccine (PCV7) was introduced, almost all (90%) young Australian Indigenous children living in remote communities had some form of otitis media (OM), including 24% with tympanic membrane perforation (TMP). In late 2009, the Northern Territory childhood vaccination schedule replaced PCV7 with 10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV10). We conducted regular surveillance of all forms of OM in children in remote Indigenous communities between September 2008 and December 2012. This analysis compares children less than 36 months of age who received a primary course of at least two doses of PCV7 or PHiD-CV10, and not more than one dose of another pneumococcal vaccine. Mean ages of 444 PCV7- and 451 PHiD-CV10-vaccinated children were 20 and 18 months, respectively. Bilaterally normal middle ears were detected in 7% and 9% respectively. OM with effusion was diagnosed in 41% and 51% (Risk Difference 10% [95% Confidence Interval 3 to 17] p = 0.002), any suppurative OM (acute OM or any TMP) in 51% versus 39% (RD -12% [95% CI -19 to -5] p = 0.0004], and TMP in 17% versus 14% (RD -3% [95% CI -8 to 2] p = 0.2), respectively. Multivariate analyses described a similar independent negative association between suppurative OM and PHiD-CV10 compared to PCV7 (Odds Ratio = 0.6 [95% CI 0.4 to 0.8] p = 0.001). Additional children in the household were a risk factor for OM (OR = 2.4 [95% CI 2 to 4] p = 0.001 for the third additional child), and older age and male gender were associated with less disease. Other measured risk factors were non-significant. Similar clinical results were found for children who had received non-mixed PCV schedules. Otitis media remains a significant health and social issue for Australian Indigenous children despite PCV vaccination. Around 90% of young children have some form of OM. Children vaccinated in with PHiD-CV10 had less suppurative OM than
Olayinka, Folake; Ewald, Leah; Steinglass, Robert
The number of vaccines available to low-income countries has increased dramatically over the last decade. Overall infant immunization coverage in the WHO African region has stagnated in the past few years while countries' ability to maintain high immunization coverage rates following introduction of new vaccines has been uneven. This case study examines post-introduction coverage among African countries that introduced PCV between 2008 and 2013 and the factors affecting Pneumococcal Conjugate Vaccine (PCV) introduction. Nearly one-third of countries did not achieve 80% infant PCV3 coverage by two years post-introduction and 58% of countries experienced a decline in coverage between post introduction years two and four. Major factors affecting coverage rates included introduction without adequate preparation, insufficient supply chain capacity and management, poor communication between organizations and with the public, and data collection systems that were insufficient to meet information needs. Deliberately addressing these issues as well as longstanding weaknesses during new vaccine introduction can strengthen the immunization and broader health system. Further study is required to identify and address factors that affect maintenance of high coverage following introduction of new vaccines in the African region. Immunization with PCV is one of the most important interventions protecting against pneumonia, the second leading cause of death for children under five globally.
Full Text Available This article presents the review of results of International conference on pneumococcal conjugated vaccines. Main results of international experience in the field of control of pneumococcal infection spreading are analyzed. Authors present modern data of clinical and economic effectiveness and safety of pneumococcal conjugated vaccine RCV-7, and describe experience of administration of vaccines of next generation – PCV-10 and PCV-13.Key words: children, pneumococcal infections, prophylaxis, vaccines.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2009;8(1:130-134
Full Text Available The optimal long-term vaccination strategies to provide population-level protection against serogroup A Neisseria meningitidis (MenA are unknown. We developed an age-structured mathematical model of MenA transmission, colonization, and disease in the African meningitis belt, and used this model to explore the impact of various vaccination strategies.The model stratifies the simulated population into groups based on age, infection status, and MenA antibody levels. We defined the model parameters (such as birth and death rates, age-specific incidence rates, and age-specific duration of protection using published data and maximum likelihood estimation. We assessed the validity of the model by comparing simulated incidence of invasive MenA and prevalence of MenA carriage to observed incidence and carriage data.The model fit well to observed age- and season-specific prevalence of carriage (mean pseudo-R2 0.84 and incidence of invasive disease (mean R2 0.89. The model is able to reproduce the observed dynamics of MenA epidemics in the African meningitis belt, including seasonal increases in incidence, with large epidemics occurring every eight to twelve years. Following a mass vaccination campaign of all persons 1-29 years of age, the most effective modeled vaccination strategy is to conduct mass vaccination campaigns every 5 years for children 1-5 years of age. Less frequent campaigns covering broader age groups would also be effective, although somewhat less so. Introducing conjugate MenA vaccine into the EPI vaccination schedule at 9 months of age results in higher predicted incidence than periodic mass campaigns.We have developed the first mathematical model of MenA in Africa to incorporate age structures and progressively waning protection over time. Our model accurately reproduces key features of MenA epidemiology in the African meningitis belt. This model can help policy makers consider vaccine program effectiveness when determining the
Harboe, Zitta Barrella; Dalby, Tine; Weinberger, Daniel M
BACKGROUND: The impact of the 13-valent pneumococcal conjugate vaccine (PCV13) at the population level is unclear. We explored PCV13's effect in reducing invasive pneumococcal disease (IPD)-related morbidity and mortality, and whether serotype-specific changes were attributable to vaccination or ...
van Werkhoven, Cornelis H; Hollingsworth, Rosalind C; Huijts, Susanne M; Bolkenbaas, Marieke; Webber, Chris; Patterson, Scott; Sanders, Elisabeth A M; Bonten, Marc J M
BACKGROUND: Herd protection from infant pneumococcal conjugate vaccination is well established for invasive pneumococcal disease (IPD) but not for non-IPD pneumococcal community-acquired pneumonia (PCAP). We assessed the contribution of vaccine-serotypes in non-IPD PCAP in adults 65 years and older
Badahdah, Al-Mamoon; Rashid, Harunor; Khatami, Ameneh
Meningitec is a CRM197-conjugated meningococcal serogroup C (MenC) vaccine, first licensed in 1999. It has been used as a primary and booster vaccine in infants, toddlers, older children and adults, and has been shown to be immunogenic and well-tolerated in all age groups, including premature infants. Vaccine effectiveness has been demonstrated using combined data on all three licensed MenC conjugate vaccines. Evidence from clinical trials, however, suggests that the different MenC conjugate vaccines behave differently with respect to the induction and persistence of bactericidal antibody and generation of immune memory. It appears that Meningitec has a less favorable immunologic profile compared particularly to tetanus toxoid (TT) MenC conjugate vaccines. Data from comparative trials have raised interesting questions on priming of the immune system by conjugate vaccines, particularly in infants. The results from these and other studies are reviewed here with specific focus on Meningitec.
de Voer, Richarda M.; van der Klis, Fiona R. M.; Engels, Carla W. A. M.; Schepp, Rutger M.; van de Kassteele, Jan; Sanders, Elisabeth A. M.; Rijkers, Ger T.; Berbers, Guy A. M.
In the Netherlands the meningococcal serogroup C conjugate (MenCC) vaccine is administered as a single dose at 14 months. We evaluated the kinetics of isotype-specific antibodies in adults (n = 21) after primary immunization with MenCC or secondary immunization with MenCC or plain MenC
Effect of Tdap when administered before, with or after the 13-valent pneumococcal conjugate vaccine (coadministered with the quadrivalent meningococcal conjugate vaccine) in adults: A randomised controlled trial.
Tashani, M; Alfelali, M; Barasheed, O; Alqahtani, A S; Heron, L; Wong, M; Rashid, H; Booy, R
Sequential or co-administration of vaccines has potential to alter the immune response to any of the antigens. Existing literature suggests that prior immunisation of tetanus/diphtheria-containing vaccines can either enhance or suppress immune response to conjugate pneumococcal or meningococcal vaccines. We examined this interaction among adult Australian travellers before attending the Hajj pilgrimage 2014. We also investigated tolerability of these vaccines separately and concomitantly. We randomly assigned each participant to one of three vaccination schedules. Group A received adult tetanus, diphtheria and acellular pertussis vaccine (Tdap) 3-4weeks before receiving CRM197-conjugated 13-valent pneumococcal vaccine (PCV13) and CRM197-conjugated quadrivalent meningococcal vaccine (MCV4). Group B received all three vaccines on one day. Group C received PCV13 and MCV4 3-4weeks before Tdap. Blood samples collected at baseline, each vaccination visit and 3-4weeks after vaccination were tested using the pneumococcal opsonophagocytic assay (OPA) and by ELISA for diphtheria and tetanus antibodies. Funding for meningococcal serology was not available. Participants completed symptom diaries after each vaccination. A total of 111 participants aged 18-64 (median 40) years were recruited. No statistically significant difference was detected across the three groups in achieving OPA titre ⩾1:8 post vaccination. However, compared to other groups, Group A had a statistically significant lower number of subjects achieving ⩾4-fold rise in serotype 3, and also significantly lower geometric mean titres (GMTs) to six (of 13) pneumococcal serotypes (3, 5, 18C, 4, 19A and 9V). Group C (given prior PCV13 and MVC4) had statistically significant higher pre-Tdap geometric mean concentration (GMC) of anti-diphtheria IgG; however, there was no difference across the three groups following Tdap. Anti-tetanus IgG GMCs were similar across the groups before and after Tdap. No serious adverse
Bergman, Annika; Hjelmgren, Jonas; Ortqvist, Ake
The 7-valent pneumococcal conjugate vaccine (PCV-7) has proved to be highly effective against invasive pneumococcal disease and has also provided some protection against all-cause pneumonia and acute otitis media. The objective of this study was to evaluate the projected health benefits, costs...... of pneumococcal septicaemia among adults. The incremental cost per QALY and LY gained was estimated to Euro 29,200 and Euro 51,400, respectively. When herd immunity was accounted for, the cost per QALYand LY gained was estimated to Euro 5500 and Euro 6600, respectively. Thus, the health benefits of a national...... and cost-effectiveness of vaccination with the 7-valent conjugated pneumococcal vaccine compared with no vaccination, in all infants in Sweden, taking herd immunity into account. A Markov model was used and a hypothetical birth cohort was simulated for a lifelong perspective. The results show...
Qian, Feng; Wu, Yimin; Muratova, Olga; Zhou, Hong; Dobrescu, Gelu; Duggan, Peter; Lynn, Lambert; Song, Guanhong; Zhang, Yanling; Reiter, Karine; MacDonald, Nicholas; Narum, David L.; Long, Carole A.; Miller, Louis H.; Saul, Allan
Conjugation of polysaccharides to carrier proteins has been a successful approach for producing safe and effective vaccines. In an attempt to increase the immunogenicity of two malarial vaccine candidate proteins of Plasmodium falciparum, apical membrane antigen 1 (AMA1) for blood stage vaccines and surface protein 25 (Pfs25) for mosquito stage vaccines, each was chemically conjugated to the mutant, nontoxic Pseudomonas aeruginosa ExoProtein A (rEPA). AMA1 is a large (66 kD) relatively good i...
van Deursen, A. M.M.; Schurink-van't Klooster, Tessa M; Man, W. H.; van de Kassteele, J.; van Gageldonk-Lafeber, Arianne B; Bruijning-Verhagen, P. C.J.L.; de Melker, Hester E.; Sanders, E. A.M.; Knol, Mirjam J.
Background The long-term impact of pneumococcal conjugate vaccines on pneumonia hospitalizations in all age-groups varies between countries. In the Netherlands, the 7-valent pneumococcal conjugate vaccine (PCV7) was implemented for newborns in 2006 and replaced by PCV10 in 2011. We assessed the
Usonis, Vytautas; Bakasenas, Vytautas; Lockhart, Stephen; Baker, Sherryl; Gruber, William; Laudat, France
CRM(197) is a carrier protein in certain conjugate vaccines. When multiple conjugate vaccines with the same carrier protein are administered simultaneously, reduced response to vaccines and/or antigens related to the carrier protein may occur. This study examined responses of infants who, in addition to diphtheria toxoid/tetanus toxoid/acellular pertussis vaccine (DTaP) received either diphtheria CRM(197)-based Haemophilus influenzae type b conjugate vaccine (HbOC) or HbOC and a diphtheria CRM(197)-based combination 9-valent pneumococcal conjugate vaccine/meningococcal group C conjugate vaccine. Administration of conjugate vaccines with CRM(197) carrier protein load >50 microg did not reduce response to CRM(197) conjugate vaccines or immunogenicity to immunologically cross-reactive diphtheria toxoid.
Pelton, Stephen I; Dagan, Ron; Gaines, Beverly M; Klugman, Keith P; Laufer, Dagna; O'Brien, Katherine; Schmitt, Heinz J
Globally, Streptococcus pneumoniae is a leading cause of invasive and noninvasive disease in infants and young children. The emergence of antibiotic-resistant strains has increased interest in prevention through immunization. Currently, the only available conjugate pneumococcal vaccine is a seven-valent formulation, PNCRM7. This paper presents excerpts from a symposium that provided an update of ongoing surveillance data and clinical trials evaluating pneumococcal conjugate vaccines. The topics addressed included: (1) PNCRM7 postmarketing safety data; (2) the impact of PNCRM7 in premature infants; (3) the direct and indirect effect of pneumococcal conjugate vaccines on colonization; (4) the effect of pneumococcal conjugate vaccines on replacement disease and the rate of resistance among replacement serotypes; (5) the current recommendations for the use of PNCRM7; and (6) the potential impact of conjugate vaccines in Europe and the Asia-Pacific region.
Kulkarni, Prasad S; Jadhav, Suresh S; LaForce, F Marc
Until recently, periodic Group A meningococcal meningitis outbreaks were a major public health problem in the sub-Saharan Africa. In 2001, the Meningitis Vaccine Project (MVP), a partnership between the World Health Organization (WHO) and PATH, a Seattle-based NGO, and the Serum Institute of India Pvt Ltd (SIIPL) initiated discussions aimed at establishing a collaboration to develop a Group A meningococcal conjugate vaccine for this unmet medical need. Over the next 8 years the partnership made countless strategic decisions about product characteristics, raw materials, potential target populations, geographic prioritization and affordability of the vaccine to name a few. These decisions evolved into detailed plans for preclinical development, extensive field trials in Africa and India and a focused regulatory strategy specific for the Men A conjugate vaccine. Important characteristics of the process included, flexibility, transparency andeffective partnerships that included public agencies as well as private companies in Africa, Europe, the United States and India.
Albert Jan van Hoek
Full Text Available Recently a large clinical trial showed that the use of 13-valent pneumococcal conjugate vaccine (PCV13 among immunocompetent individuals aged 65 years and over was safe and efficacious. The aim of this study was to assess the cost-effectiveness of vaccinating immunocompetent 65 year olds with PCV13 vaccine in England. England is a country with universal childhood pneumococcal conjugate vaccination programme in place (7-valent (PCV7 since 2006 and PCV13 since 2010, as well as a 23-valent pneumococcal polysaccharide (PPV23 vaccination programme targeting clinical risk-groups and those ≥65 years.A static cohort cost-effectiveness model was developed to follow a cohort of 65 year olds until death, which will be vaccinated in the autumn of 2016 with PCV13. Sensitivity analysis was performed to test the robustness of the results.The childhood vaccination programme with PCV7 has induced herd protection among older unvaccinated age groups, with a resultant low residual disease burden caused by PCV7 vaccine types. We show similar herd protection effects for the 6 additional serotypes included in PCV13, and project a new low post-introduction equilibrium of vaccine-type disease in 2018/19. Applying these incidence projections for both invasive disease and community-acquired pneumonia (CAP, and using recent measures of vaccine efficacy against these endpoints for ≥65 year olds, we estimate that vaccination of a cohort of immunocompetent 65 year olds with PCV13 would directly prevent 26 cases of IPD, 69 cases of CAP and 15 deaths. The associated cost-effectiveness ratio is £257,771 per QALY gained (using list price of £49.10 per dose and £7.51 administration costs and is therefore considered not cost-effective. To obtain a cost-effective programme the price per dose would need to be negative. The results were sensitive to disease incidence, waning vaccine protection and case fatality rate; despite this, the overall conclusion was robust.Vaccinating
Ma, Fu-Bao; Tao, Hong; Wang, Hong-Jun
To evaluate the Immunogenicity of Group A and Group C Meningococcal conjugate Vaccine with coupling Group B Meningococcal Outer Membrane Protein (Men B-OMP). 458 healthy children aged 3-5 months, 6-23 months, 2-6 years and 7-24 years were given the Groups A and C conjugate Vaccine with MenB-OMP or other vaccine as control group to measure the pre-and post-vaccination Men A and C and B by Serum Bactericidal Assay (SBA) in the double-blind randomized controlled trial. 97.65%-100% were 4 times or greater increase in SBA titer for the healthy children given the Groups A and C conjugate Vaccine with MenB-OMP, The geometric mean titer of SBA were 1:194-1:420, which significantly higber than controls. The Group A and C conjugate Vaccine with MenB-OMP was safe and well immunogenic.
Constenla, Dagna O
To evaluate the economic impact of vaccination with the pneumococcal 7-valent conjugate vaccine (PCV7) in Brazil, Chile, and Uruguay. A decision analytic model was constructed to compare pneumococcal vaccination of children 0-5 years old with no vaccination in Brazil, Chile, and Uruguay. Costs and health outcomes were analyzed from the societal perspective. Vaccine, demographic, epidemiologic, and cost data were incorporated into this economic analysis. At the rate of diphtheria-tetanus-pertussis (DTP) vaccine coverage and a vaccine price of US$ 53 per dose, PCV7 was projected to prevent 23 474 deaths per year in children under 5 years old in the three countries studied, thus averting 884,841 disability-adjusted life years (DALYs) yearly. To vaccinate the entire birth cohort of the three countries, total vaccine costs would be US$ 613.9 million. At US$ 53 per dose, the cost per DALY averted from a societal perspective would range from US$ 664 (Brazil) to US$ 2019 (Chile). At a cost of US$ 10 per dose, vaccine cost is lower than the overall cost of illness averted (US$ 125,050,497 versus US$ 153,965,333), making it cost effective and cost-saving. The results of this study demonstrate that the incorporation of PCV7 vaccine at US$ 53 per dose confers health benefits at extra costs. It is unclear whether vaccinatfon at the current price is affordable to these countries.
Tetanus-diphtheria-pertussis vaccine may suppress the immune response to subsequent immunization with pneumococcal CRM197-conjugate vaccine (coadministered with quadrivalent meningococcal TT-conjugate vaccine): a randomized, controlled trial⋆.
Tashani, Mohamed; Heron, Leon; Wong, Melanie; Rashid, Harunor; Booy, Robert
: Due to their antigenic similarities, there is a potential for immunological interaction between tetanus/diphtheria-containing vaccines and carrier proteins presented on conjugate vaccines. The interaction could, unpredictably, result in either enhancement or suppression of the immune response to conjugate vaccines if they are injected soon after or concurrently with diphtheria or tetanus toxoid. We examined this interaction among adult Australian travellers before attending the Hajj pilgrimage of 2015. We randomly assigned each participant to one of three vaccination schedules. Group A received tetanus, diphtheria and acellular pertussis vaccine (Tdap) 3-4 weeks before receiving CRM197-conjugated 13-valent pneumococcal vaccine (PCV13) coadministered with TT-conjugated quadrivalent meningococcal vaccine (MCV4). Group B received all three vaccines concurrently. Group C received PCV13 and MCV4 3-4 weeks before Tdap. Blood samples collected at baseline, at each vaccination visit and 3-4 weeks after vaccination were tested for the pneumococcal opsonophagocytic assay (OPA). A total of 166 participants aged 18-64 (median 42) years were recruited, 159 completed the study. Compared with the other groups, Group A had significantly ( P vaccination in seven serotypes of PCV13 (1, 3, 4, 5, 14, 18C and 9V). Additionally, Group A had lower frequency of serorises (≥ 4-fold rise in OPA titres) in serotype5 (79%, p = 0.01) and 18C (73.5%, p = 0.06); whereas Groups B and C had significantly lower frequencies of serorises in Serotype 4 (82%) and 6A (73.5%), respectively. No statistically significant difference was detected across the three groups in frequencies achieving OPA titre ≥ 1:8 post-vaccination. Tdap vaccination 3-4 weeks before administration of PCV13 and MCV4 significantly reduced the GMTs to seven of the 13 pneumococcal serotypes in adults. If multiple vaccination is required before travel, deferring tetanus/diphtheria until after administering the
Wasserman, Matt; Wilson, Michele; McDade, Cheryl; Grajales, Ana Gabriela; Palacios, Maria Gabriela; Baez- Revueltas, Fabiola Berenice; Farkouh, Raymond
Abstract Background PCV13 replaced 7-valent pneumococcal conjugate vaccine in the routine infant immunization schedule in Mexico since 2011. The use of PCV13 has reduced pneumococcal disease incidence for vaccine serotypes, particularly 19A, which emerged following PCV7 use. The 10-valent vaccine (PCV10) contains the same serotypes as PCV13 with the exception of serotypes 3, 19A and 6A but also has different conjugated proteins for the common serotypes. This study evaluated the potential heal...
Safety and immunogenicity of coadministering a combined meningococcal serogroup C and Haemophilus influenzae type b conjugate vaccine with 7-valent pneumococcal conjugate vaccine and measles, mumps, and rubella vaccine at 12 months of age.
Miller, Elizabeth; Andrews, Nick; Waight, Pauline; Findlow, Helen; Ashton, Lindsey; England, Anna; Stanford, Elaine; Matheson, Mary; Southern, Joanna; Sheasby, Elizabeth; Goldblatt, David; Borrow, Ray
The coadministration of the combined meningococcal serogroup C conjugate (MCC)/Haemophilus influenzae type b (Hib) vaccine with pneumococcal conjugate vaccine (PCV7) and measles, mumps, and rubella (MMR) vaccine at 12 months of age was investigated to assess the safety and immunogenicity of this regimen compared with separate administration of the conjugate vaccines. Children were randomized to receive MCC/Hib vaccine alone followed 1 month later by PCV7 with MMR vaccine or to receive all three vaccines concomitantly. Immunogenicity endpoints were MCC serum bactericidal antibody (SBA) titers of ≥8, Hib-polyribosylribitol phosphate (PRP) IgG antibody concentrations of ≥0.15 μg/ml, PCV serotype-specific IgG concentrations of ≥0.35 μg/ml, measles and mumps IgG concentrations of >120 arbitrary units (AU)/ml, and rubella IgG concentrations of ≥11 AU/ml. For safety assessment, the proportions of children with erythema, swelling, or tenderness at site of injection or fever or other systemic symptoms for 7 days after immunization were compared between regimens. No adverse consequences for either safety or immunogenicity were demonstrated when MCC/Hib vaccine was given concomitantly with PCV and MMR vaccine at 12 months of age or separately at 12 and 13 months of age. Any small differences in immunogenicity were largely in the direction of a higher response when all three vaccines were given concomitantly. For systemic symptoms, there was no evidence of an additive effect; rather, any differences between schedules showed benefit from the concomitant administration of all three vaccines, such as lower overall proportions with postvaccination fevers. The United Kingdom infant immunization schedule now recommends that these three vaccines may be offered at one visit at between 12 and 13 months of age.
Studies evaluating a 9-valent PCV in South Africa and The Gambia reported a 72 - 77% reduction in vaccineserotype- specific invasive disease in vaccinated children. As many of the pneumococcal serotypes associated with antibiotic resistance are included in PCV, vaccination has also been associated with a reduction in ...
Öbrink-Hansen, Kristina; Søgaard, Ole S; Harboe, Zitta B
HIV-infected individuals have excess rates of invasive pneumococcal disease. We investigated risk factors for nasopharyngeal pneumococcal colonization at baseline and after 9 months in 96 HIV patients immunized twice with 7- valent pneumococcal conjugate vaccine ±1mg CPG 7909. In total, 22 patients...
Gargano, Lisa M; Hajjeh, Rana; Cookson, Susan T
Pneumonia is a leading cause of death among children less than five years old during humanitarian emergencies. Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae are the leading causes of bacterial pneumonia. Vaccines for both of these pathogens are available to prevent pneumonia. Problem This study describes an economic analysis from a publicly funded health care system perspective performed on a birth cohort in Somalia, a country that has experienced a protracted humanitarian emergency. An impact and cost-effectiveness analysis was performed comparing: no vaccine, Hib vaccine only, pneumococcal conjugate vaccine 10 (PCV10) only, and both together administered through supplemental immunization activities (SIAs). The main summary measure was the incremental cost per disability-adjusted life-years (DALYs) averted. One-way sensitivity analysis was conducted for uncertainty in parameter values. Each SIA would avert a substantial number of cases and deaths. Compared with no vaccine, the DALYs averted by two SIAs for two doses of Hib vaccine was US $202.93 (lower and upper limits: $121.80-$623.52), two doses of PCV10 was US $161.51 ($107.24-$227.21), and two doses of both vaccines was US $152.42 ($101.20-$214.42). Variables that influenced the cost-effectiveness for each strategy most substantially were vaccine effectiveness, case fatality rates (CFRs), and disease burden. The World Health Organization (WHO) defines a cost-effective intervention as costing one to three times the per capita gross domestic product (GDP; in 2011, for Somalia=US $112). Based on the presented model, Hib vaccine alone, PCV10 alone, or Hib vaccine and PCV10 given together in SIAs are cost-effective interventions in Somalia. The WHO/Strategic Advisory Group of Experts decision-making factors for vaccine deployment appear to have all been met: the disease burden is large, the vaccine-related risk is low, prevention in this setting is more feasible than treatment, the vaccine
Full Text Available Abstract Background The first meningococcal serogroup C (MenC conjugate vaccine was licensed in 1999 and introduced in the United Kingdom. Countries that have implemented the MenC vaccine since then in their national immunisation programmes use different schedules. Nevertheless, all involved countries seem to experience substantial declines in the incidence of MenC disease. Discussion Since 2001, the MenC conjugate vaccine has been implemented in the Netherlands by offering a single dose to all children aged 14 months. Prior to the introduction of the vaccine into the national immunisation programme, a catch-up vaccination campaign was initiated in which a single dose of the MenC conjugate vaccine was offered to all children aged from 14 months up to and including 18 years. Since then, there has been no report of any case of MenC disease among immunocompetent vaccinees. Administration of a single dose of MenC conjugate vaccine after infancy could be beneficial considering the already complex immunisation schedules with large numbers of vaccinations in the first year of life. The present paper deals with the advantages and critical aspects of a single dose of the MenC conjugate vaccine. Summary A single dose of MenC conjugate vaccine at the age of 14 months in combination with a catch up vaccine campaign appeared to be a successful strategy to prevent MenC disease in the Netherlands, thereby confirming that a single dose of the vaccine could sufficiently protect against disease. Nevertheless, this approach can only be justified in countries with a relatively low incidence of serogroup C meningococcal disease in the first year of life. Furthermore, a good surveillance programme is recommended for timely detection of vaccine breakthroughs and outbreaks among non-vaccinees, since long-term protection after a single dose in the second year of life cannot currently be guaranteed.
Fletcher, Mark A.; Fritzell, Bernard
Streptococcus pneumoniae is the predominant otitis media pathogen and its prevention through effective vaccination could diminish childhood illness and antibiotic use. This paper reviews 5 pneumococcal conjugate vaccine (PCV) trials that used otitis media as an endpoint: Northern California Kaiser Permanente (NCKP; vaccine, 7-valent PCV [PCV7]-CRM); Finnish Otitis Media (FinOM; vaccines, PCV7-CRM or PCV7-OMPC); Native American Trial (vaccine, PCV7-CRM); Pneumococcal Otitis Efficacy Trial (POET; vaccine, 11-valent PCV [PCV11]-PD). For the microbiological endpoint, vaccine efficacy against vaccine-serotype pneumococcal otitis media was about 60% across trials. Against the clinical endpoint of all episodes, vaccine efficacy was 7% (PCV7-CRM/NCKP), 6% (PCV7-CRM/FinOM), −1% (PCV7-OMPC/FinOM), and −0.4% (PCV7-CRM/Native American Trial); 34% against first episodes of ear, nose, and throat specialist-referral cases (PCV11-PD/POET). Both follow-up through 2 years of age, for the 5 trials, and long-term follow-up, for PCV7-CRM/NCKP and PCV7-CRM/FinOM, demonstrated greater vaccine efficacy against recurrent AOM and tympanostomy-tube placement, suggesting that vaccination against early episodes of AOM may prevent subsequent episodes of complicated otitis media. Although study designs varied by primary endpoint measured, age at follow-up, source of middle-ear fluid for culture, case ascertainment, and type of randomization, each clinical trial demonstrated vaccine efficacy against microbiological and/or clinical otitis media. PMID:22701486
Ciruela, Pilar; Martínez, Ana; Izquierdo, Conchita; Hernández, Sergi; Broner, Sonia; Muñoz-Almagro, Carmen; Domínguez, Àngela; of Catalonia Study Group, the Microbiological Reporting System
We investigated the incidence and distribution of cases of invasive pneumococcal disease (IPD), invasive meningococcal disease (IMD) and invasive Hemophilus influenzae disease (IHiD) notified by hospital laboratories to the Microbiological Reporting System of Catalonia between 2005 and 2009. Incidence rates were compared using the rate ratio (RR) and 95% CI were calculated. A value of p cases, 6,012 were IPD, 436 IMD and 213 IHiD. The global annual incidence per 105 inhabitants was 16.62 (95% CI 16.20–17.04) for IPD, 1.21 (95% CI 1.09–1.32) for IMD and 0.59 (95% CI 0.51–0.67) for IHiD. IPD increased in 2009 compared with 2005 (RR:1.55, 95%CI: 1.43–1.70) and IMD and IHiD remained stable. Pneumonia was the most-frequent clinical manifestation of IPD (75.6%) and IHiD (44.1%) and meningoencephalitis with or without sepsis for IMD (70.6%). The male:female ratio was 1.37 for IPD, 1.0 for IMD and 1.15 for IHiD. The age groups with the highest incidence were the ≤ 2 y and 2–4 y groups for IPD (66.40 and 50.66/100,000 persons-year) and IMD (14.88 and 7.26/100,000 persons-year) and the ≤ 2 y and ≥ 65 y groups for IHiD (1.88 and 1.89/100,000 persons-year). The most-frequent serotypes were serotype 1 (19.0%) in IPD and untypeable serotypes (60.8%) in IHiD. Serogroup B (78.3%) was the most frequent in IMD. S. pneumoniae is the most-frequent agent causing invasive disease in Catalonia. The main clinical manifestations were pneumonia in IPD and IHiD and meningitis in IMD. The main causative agent of meningitis was N. meningitidis in people aged < 20 y and S. pneumoniae in people aged ≥ 20 y. Vaccination with conjugate vaccines may reduce the risk of infectious disease in our setting. PMID:23303166
Bahadoran, Azadeh; Moeini, Hassan; Bejo, Mohd Hair; Hussein, Mohd Zobir; Omar, Abdul Rahman
In order to enhance cellular uptake and to facilitate transdermal delivery of DNA vaccine, polyamidoamine (PAMAM) dendrimers conjugated with HIV transactivator of transcription (TAT) was developed. First, the plasmid DNA (pIRES-H5/GFP) nanoparticle was formulated using PAMAM dendrimer and TAT peptide and then characterized for surface charge, particle size, DNA encapsulation and protection of the pIRES-H5/GFP DNA plasmid to enzymatic digestion. Subsequently, the potency of the TAT-conjugated dendrimer for gene delivery was evaluated through in vitro transfection into Vero cells followed by gene expression analysis including western blotting, fluorescent microscopy and PCR. The effect of the TAT peptide on cellular uptake of DNA vaccine was studied by qRT-PCR and flow cytometry. Finally, the ability of TAT-conjugated PAMAM dendrimer for transdermal delivery of the DNA plasmid was assessed through artificial membranes followed by qRT-PCR and flow cytometry. TAT-conjugated PAMAM dendrimer showed the ability to form a compact and nanometre-sized polyplexes with the plasmid DNA, having the size range of 105 to 115 nm and a positive charge of +42 to +45 mV over the N/P ratio of 6:1(+/-). In vitro transfection analysis into Vero cells confirms the high potency of TAT-conjugated PAMAM dendrimer to enhance the cellular uptake of DNA vaccine. The permeability value assay through artificial membranes reveals that TAT-conjugated PAMAM has more capacity for transdermal delivery of the DNA compared to unmodified PAMAM dendrimer (Pdendrimer is a promising non-viral vector for transdermal use.This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.
In 2010, vaccines have achieved good effectiveness against invasive meningococcal infection. Development of monovalent and bivalent polysaccharide (PS) vaccines in the 70s and later of tetravalent PS vaccine (ACWY) was followed by development in 2003 of a trivalent ACW vaccine in response to the W135 or mixed A/W135 epidemics that appeared in Africa. More recently PS-conjugated vaccines have shown numerous advantages in comparison with PS vaccines. Mass vaccination campaigns with the C-conjugated vaccine have almost completely eradicated group C meningitis in the UK. It is hoped that introduction of the A-conjugated vaccine MenAfriVac in Africa at the end of year 2010 will end group A meningococcal epidemics in the meningitis belt. The problem of group B meningococcal meningitis has not been completely resolved. For the B strain that has been implicated in hyperendemic waves, a protein vaccine has been produced from outer membrane vesicles (OMV). Use of OMV vaccines achieved good results in Norway and recently in New Zealand. The Norwegian vaccine was also used in Normandy since the strain responsible for the Norman epidemic showed the same PorA as the Norwegian strain. In this regard, a major limitation for OMV vaccines is that they are effective only against the immuno-dominant porin A protein. Current efforts to develop a vaccine against group B meningococci causing sporadic cases are promising. Research is being focused on a blend of surface proteins targeting most of circulating isolates. Field tests will be carried out in the next years, but it is probable that the efficacy of these vaccines will be short-lived since meningococcal antigens vary over time.
Lai, Zengzu; Schreiber, John R
Bacterial polysaccharides (PS) are T cell-independent antigens that do not induce immunologic memory and are poor immunogens in infants. Conjugate vaccines in which the PS is covalently linked to a carrier protein have enhanced immunogenicity that resembles that of T cell-dependent antigens. The Haemophilus influenzae type b (Hib) conjugate vaccine, which uses the outer membrane protein complex (OMPC) from meningococcus as a carrier protein, elicits protective levels of anti-capsular PS antibody (Ab) after a single dose, in contrast to other conjugate vaccines, which require multiple doses. We have previously shown that OMPC robustly engages Toll-like receptor 2 (TLR2) and enhances the early anti-Hib PS Ab titer associated with an increase in TLR2-mediated induction of cytokines. We now show that the addition of OMPC to the 7-valent pneumococcal PS-CRM₁₉₇ conjugate vaccine during immunization significantly increases the anti-PS IgG and IgM responses to most serotypes of pneumococcus contained in the vaccine. The addition of OMPC also increased the likelihood of anti-PS IgG3 production against serotypes 4, 6B, 9V, 18C, 19F, and 23F. Splenocytes from mice who had received OMPC with the pneumococcal conjugate vaccine produced significantly more interleukin-2 (IL-2), IL-4, IL-6, IL-10, tumor necrosis factor alpha (TNF-α), and gamma interferon (IFN-γ) than splenocytes from mice who received phosphate-buffered saline (PBS) plus the conjugate vaccine. We conclude that OMPC enhances the anti-PS Ab response to pneumococcal PS-CRM₁₉₇ conjugate vaccine, an effect associated with a distinct change in cytokine profile. It may be possible to reduce the number of conjugate vaccine doses required to achieve protective Ab levels by priming with adjuvants that are TLR2 ligands.
van Hoek, Albert Jan; Choi, Yoon Hong; Trotter, Caroline; Miller, Elizabeth; Jit, Mark
In the immunisation schedule in England and Wales, the 7-valent pneumococcal conjugate vaccine (PCV-7) was replaced by the 13-valent vaccine (PCV-13) in April 2010 after having been used since September 2006. The introduction of PCV-7 was informed by a cost effectiveness analysis using an infectious disease model which projected herd immunity and serotype replacement effects based on the post-vaccine experience in the United States at that time. To investigate the cost effectiveness of the introduction of PCV-13. Invasive disease incidence following vaccination was projected from a dynamic infectious disease model, and combined with serotype specific disease outcomes obtained from a large hospital dataset linked to laboratory confirmation of invasive pneumococcal disease. The economic impact of replacing PCV-7 with PCV-13 was compared to stopping the use of pneumococcal conjugate vaccination altogether. Discontinuing PCV-7 would lead to a projected increase in invasive pneumococcal disease, costs and loss of quality of life compared to the introduction of PCV-13. However under base case assumptions (assuming no impact on non-invasive disease, maximal competition between vaccine and non-vaccine types, time horizon of 30 years, vaccine price of £49.60 a dose+£7.50 administration costs and discounting of costs and benefits at 3.5%) the introduction of PCV-13 is only borderline cost effective compared to a scenario of discontinuing of PCV-7. The intervention becomes more cost-effective when projected impact of non-invasive disease is included or the discount factor for benefits is reduced to 1.5%. To our knowledge this is the first evaluation of a transition from PCV-7 to PCV-13 based on a dynamic model. The cost-effectiveness of such a policy change depends on a number of crucial assumptions for which evidence is limited, particularly the impact of PCV-13 on non-invasive disease. Copyright © 2012 Elsevier Ltd. All rights reserved.
Ganda, Ingrid S; Zhong, Qian; Hali, Mirabela; Albuquerque, Ricardo L C; Padilha, Francine F; da Rocha, Sandro R P; Whittum-Hudson, Judith A
Peptide-based vaccines have emerged in recent years as promising candidates in the prevention of infectious diseases. However, there are many challenges to maintaining in vivo peptide stability and enhancement of peptide immunogenicity to generate protective immunity which enhances clearance of infections. Here, a dendrimer-based carrier system is proposed for peptide-based vaccine delivery, and shows its anti-microbial feasibility in a mouse model of Chlamydia trachomatis. Chlamydiae are the most prevalent sexually transmitted bacteria worldwide, and also the causal agent of trachoma, the leading cause of preventable infectious blindness. In spite of the prevalence of this infectious agent and the many previous vaccine-related studies, there is no vaccine commercially available. The carrier system proposed consists of generation 4, hydroxyl-terminated, polyamidoamine (PAMAM) dendrimers (G4OH), to which a peptide mimic of a chlamydial glycolipid antigen-Peptide 4 (Pep4, AFPQFRSATLLL) was conjugated through an ester bond. The ester bond between G4OH and Pep4 is expected to break down mainly in the intracellular environment for antigen presentation. Pep4 conjugated to dendrimer induced Chlamydia-specific serum antibodies after subcutaneous immunizations. Further, this new vaccine formulation significantly protected immunized animals from vaginal challenge with infectious Chlamydia trachomatis, and it reduced infectious loads and tissue (genital tract) damage. Pep4 conjugated to G4OH or only mixed with peptide provided enhanced protection compared to Pep4 and adjuvant (i.e. alum), suggesting a potential adjuvant effect of the PAMAM dendrimer. Combined, these results demonstrate that hydroxyl-terminated PAMAM dendrimer is a promising polymeric nanocarrier platform for the delivery of peptide vaccines and this approach has potential to be expanded to other infectious intracellular bacteria and viruses of public health significance. Copyright © 2017 Elsevier B.V. All
Barington, T; Skettrup, M; Juul, L
children and adults. Despite its potential importance, the possible influence of preexisting immunity to the components of such conjugates on the vaccination response in humans has been addressed by few studies. To study this issue, we randomized 82 healthy adult volunteers into six groups and vaccinated......Recently, conjugate vaccines containing Haemophilus influenzae type b capsular polysaccharide (HibCP) coupled to protein carriers were introduced for use in infants and certain adult risk groups. Similar conjugate vaccines against other capsulated bacteria are currently under development for both......CP-TT, P = 0.00002; HibCP-TT and then HibCP-DT, P = 0.06) as well as to HibCP itself. Possible mechanisms behind this non-epitope-specific suppression and its relevance for vaccine development are discussed....
O'Connor, Daniel; Clutterbuck, Elizabeth A; Thompson, Amber J; Snape, Matthew D; Ramasamy, Maheshi N; Kelly, Dominic F; Pollard, Andrew J
Neisseria meningitidis is a globally important cause of meningitis and septicaemia. Twelve capsular groups of meningococci are known, and quadrivalent vaccines against four of these (A, C, W and Y) are available as plain-polysaccharide and protein-polysaccharide conjugate vaccines. Here we apply contemporary methods to describe B-cell responses to meningococcal polysaccharide and conjugate vaccines. Twenty adults were randomly assigned to receive either a meningococcal plain-polysaccharide or conjugate vaccine; one month later all received the conjugate vaccine. Blood samples were taken pre-vaccination and 7, 21 and 28 days after vaccination; B-cell responses were assessed by ELISpot, serum bactericidal assay, flow cytometry and gene expression microarray. Seven days after an initial dose of either vaccine, a gene expression signature characteristic of plasmablasts was detectable. The frequency of newly generated plasma cells (CXCR3 + HLA-DR + ) and the expression of transcripts derived from IGKC and IGHG2 correlated with immunogenicity. Notably, using an independent dataset, the expression of glucosamine (N-acetyl)-6-sulfatase was found to reproducibly correlate with the magnitude of immune response. Transcriptomic and flow cytometric data revealed depletion of switched memory B cells following plain-polysaccharide vaccine. These data describe distinct gene signatures associated with the production of high-avidity antibody and a plain-polysaccharide-specific signature, possibly linked to polysaccharide-induced hyporesponsiveness.
Morales, Desirée; García-Cenoz, Manuel; Moreno, Laura; Bernaola, Enrique; Barricarte, Aurelio; Castilla, Jesús
Since 2000, when the meningococcal serogroupC conjugate vaccine (MenCC) was introduced in the childhood immunization schedule in Spain, several changes in the schedule and catch-up campaigns have been performed. We aim to estimate the impact and effectiveness of this vaccine in Navarra up to 2014. The impact of the vaccination program was analysed by comparing incidence, mortality and lethality rates of disease before (1995-1999) and after (2004-2014) the introduction of the MenCC. Vaccine effectiveness was estimated using the screening method (Farrington) and the indirect cohort method (Broome). Data on cases were obtained from the active surveillance of meningococcal disease. During 1995-1999 the mean annual incidence of meningococcalC disease was 1.32 per 100,000, and 7.18 per 100,000 in children younger than 15years. The fall of meningococcalC disease incidence was significant in cohorts targeted for vaccination from the beginning and progressive in the general population. No cases were reported between 2011 and 2014. The estimated vaccine effectiveness was 96% by the screening method, and 99% by the indirect cohort method. The MenCC vaccination program has been successful in decreasing the incidence rate of serogroupC meningococcal disease in Navarra, and schedule changes have maintained high vaccine effectiveness throughout the study period. Copyright Â© 2015 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.
van Westen, Els; Wijmenga-Monsuur, Alienke J; van Dijken, Harry H; van Gaans-van den Brink, Jacqueline A M; Kuipers, Betsy; Knol, Mirjam J; Berbers, Guy A M; Sanders, Elisabeth A M; Rots, Nynke Y; van Els, Cécile A C M
BACKGROUND: Both the 10- and 13-valent pneumococcal conjugate vaccines (PCV10 and PCV13) induce immunological memory against Streptococcus pneumoniae infections caused by vaccine serotypes. In addition to comparing serum antibody levels, we investigated frequencies of serotype-specific plasma cells
Effects of influenza plus pneumococcal conjugate vaccination versus influenza vaccination alone in preventing respiratory tract infections in children : a randomized, double-blind, placebo-controlled trial
Jansen, Angelique G S C; Sanders, Elisabeth A M; Hoes, Arno W; van Loon, Anton M; Hak, Eelko
OBJECTIVE: To evaluate the effects of influenza vaccination with or without heptavalent pneumococcal conjugate vaccination on respiratory tract infections (RTIs) in children. STUDY DESIGN: This was a randomized, double-blind, placebo-controlled trial comprising 579 children age 18 to 72 months with
M. V. Fedoseenko
Full Text Available Compulsory use of the 7-valent pneumococcal conjugate vaccine in the framework of national pediatric immunization schedules of the developed countries resulted in significant decrease in the prevalence of the pneumococcal infections induced by the vaccinal serotypes. However, a growth in prevalence of the pneumonia and acute otitis media caused by non-vaccinal strains has also been observed. This required introduction of a new 13-valent pneumococcal conjugate vaccine with a wider range of pneumococcal population coverage. The experience of application accumulated in various countries (2010 onwards and results of the authors’ observations indicate high safety of the 13-valent pneumococcal conjugate vaccine for both healthy under-5 children and patients with various medical issues. The article presents results of the 13-valent pneumococcal conjugate vaccination tolerance assessment. The study involved 110 children from 2 months to 5 years of age. In most cases immunization concurred with other pediatric vaccines. The incidence of local reactions in vaccinated children did not exceed 33%, of generalized reactions – 11%. The authors observed a comparable incidence of side reactions in both virtually healthy children and children with various medical issues.
Tatiane E. Hirose
Conclusion: Even after a short time of use, the 10‐valent pneumococcal conjugate vaccine has already had a significant impact in reducing the incidence and mortality of meningitis cases among infants, as well as the reduction of cases whose serotypes are included in the vaccine.
Taylor, Sylvia; Marchisio, Paola; Vergison, Anne; Harriague, Julie; Hausdorff, William P.; Haggard, Mark
Acute otitis media (AOM) is a leading cause of visits to physicians and of antibiotic prescriptions for young children. We systematically reviewed studies on all-cause AOM episodes and physician visits in which impact was attributed to pneumococcal conjugate vaccines, either as efficacy or effectiveness. Of 18 relevant publications found, most used the 7-valent pneumococcal conjugate vaccine (7vCRM). The efficacy of 7vCRM against all-cause AOM episodes or visits was 0%–9% in randomized trials and 17%–23% in nonrandomized trials. In observational database studies, physician visits for AOM were already declining in the 3–5 years before 7vCRM introduction (mean change, −15%; range, +14% to −24%) and continued to decline afterward (mean, −19%; range, +7% to −48%). This vaccine provides some protection against OM, but other factors have also contributed to the recent decline in OM incidence. Future effectiveness studies should thus use better-controlled methods to estimate the true impact of vaccination on AOM. PMID:22423134
Micoli, F; Rondini, S; Pisoni, I; Proietti, D; Berti, F; Costantino, P; Rappuoli, R; Szu, S; Saul, A; Martin, L B
An efficacious, low cost vaccine against typhoid fever, especially for young children, would make a major impact on disease burden in developing countries. The virulence capsular polysaccharide of Salmonella Typhi (Vi) coupled to recombinant mutant Pseudomonas aeruginosa exoprotein A (Vi-rEPA) has been shown to be highly efficacious. We investigated the use of carrier proteins included in infant vaccines, standardized the conjugation process and developed key assays required for routine lot release at production scale. Vi from a BSL1 organism, Citrobacter freundii, strain WR7011, was used as an alternative to Vi from S. Typhi. We showed that Vi conjugated to CRM(197), a non-toxic mutant of diphtheria toxin, widely used in commercial vaccines, was produced at high yield. Vi-CRM(197) proved immunogenic in animal studies, even without adjuvant. Thus, Vi-CRM(197) appears to be a suitable candidate for the development of a commercially viable, effective typhoid vaccine for developing countries. Copyright Â© 2010 Elsevier Ltd. All rights reserved.
James B Wing
Full Text Available Despite the success of conjugate vaccination against meningococcal group C (MenC disease, post-vaccination, some individuals still exhibit rapid waning of initially protective bactericidal antibody levels. The mechanism of this relative loss of humoral protection remains undetermined. In this report we have investigated the relationship between T- and B-cell activation and co-stimulation and the loss of protective antibody titers. We have found that healthy volunteers who lose protective MenC antibody levels one year after receipt of glycoconjugate vaccine exhibit no detectable cellular defect in polyclonal B- or T-cell activation, proliferation or the B-memory pool. This suggests that the processes underlying the more rapid loss of antibody levels are independent of defects in either initial T- or B-cell activation.
Stevens, Misty W; Gunnell, Melinda G; Tawney, Rachel; Owens, S Michael
There are still no approved medications for treating patients who abuse methamphetamine. Active vaccines for treating abuse of nicotine and cocaine are in clinical studies, but have not proven effective seemingly due to inadequate anti-drug antibody production. The current studies aimed to optimize the composition, adjuvant and route of administration of a methamphetamine conjugate vaccine, ICKLH-SMO9, in mice with the goal of generating significantly higher antibody levels. A range of hapten epitope densities were compared, as were the adjuvants Alhydrogel and a new Toll-like receptor 4 (TLR4) agonist called GLA-SE. While methamphetamine hapten density did not strongly affect the antibody response, the adjuvant did. Glucopyranosyl lipid A in a stable oil-in-water emulsion (GLA-SE) produced much higher levels of antibody in response to immunization compared with Alhydrogel; immunization with GLA-SE also produced antibodies with higher affinities for methamphetamine. GLA-SE has been used in human studies of vaccines for influenza among others and like some other clinical TLR4 agonists, it is safe and elicits a strong immune response. GLA-SE adjuvanted vaccines are typically administered by intramuscular injection and this also proved effective in these mouse studies. Clinical studies of the ICKLH-SMO9 methamphetamine vaccine adjuvanted with GLA-SE have the potential for demonstrating efficacy by generating much higher levels of antibody than substance abuse vaccines that have unsuccessfully used aluminum-based adjuvants. Copyright © 2016 Elsevier B.V. All rights reserved.
Full Text Available A new pneumococcal conjugate vaccine is currently undergoing advanced clinical evaluation prior to its planned introduction in Cuba. The implementation of the pneumococcal vaccination strategy has been designed with consideration of the need to maximize both its direct and indirect effects. A novel approach is suggested, which addresses preschool children as the first-line target group to generate herd immunity in infants and to have an impact on transmission at the community level. The clinical evaluation pipeline is described herein, including evaluations of effectiveness, cost-effectiveness, and impact. The scientific contribution of the Cuban strategy could support a paradigm shift from individual protection to a population effect based on a rigorous body of scientific evidence.
Velentgas, Priscilla; Amato, Anthony A; Bohn, Rhonda L; Chan, K Arnold; Cochrane, Thomas; Funch, Donnie P; Dashevsky, Inna; Duddy, April L; Gladowski, Patricia; Greenberg, Steven A; Kramer, Judith M; McMahill-Walraven, Cheryl; Nakasato, Cynthia; Spettell, Claire M; Syat, Beth L; Wahl, Peter M; Walker, Alexander M; Zhang, Fang; Brown, Jeffrey S; Platt, Richard
A new meningococcal conjugate vaccine (MCV4) was introduced in 2005. Shortly after, case reports of Guillain-Barré syndrome (GBS), a serious demyelinating disease, began to be reported to the Vaccine Adverse Event Reporting System. In 2006, the Centers for Disease Control and Prevention and the Food and Drug Administration requested the evaluation of GBS risk after MCV4 vaccination. We conducted a study to assess the risk of GBS after MCV4 vaccination using health plan administrative and claims data together with the review of primary medical records of potential cases. Retrospective cohort study among 12.6 million 11- to 21-year-old members of five US health plans with a total membership of 50 million. Automated enrollment and medical claims data from March 2005 through August 2008 were used to identify the population, the vaccinations administered, and the medical services associated with possible GBS. Medical records were reviewed and adjudicated by a neurologist panel to confirm cases of GBS. The study used distributed data analysis methods that minimized sharing of protected health information. We confirmed 99 GBS cases during 18,322,800 person-years (5.4/1,000,000 person-years). More than 1.4 million MCV4 vaccinations were observed. No confirmed cases of GBS occurred within 6 weeks after vaccination. The upper 95% CI for the attributable risk of GBS associated with MCV4 is estimated as 1.5 cases per 1,000,000 doses. Among members of five US health plans, MCV4 vaccination was not associated with increased GBS risk. Copyright © 2012 John Wiley & Sons, Ltd.
Diez-Domingo, Javier; Gurtman, Alejandra; Bernaola, Enrique; Gimenez-Sanchez, Francisco; Martinon-Torres, Federico; Pineda-Solas, Valentin; Delgado, Alfonso; Infante-Marquez, Pilar; Liang, John Z; Giardina, Peter C; Gruber, William C; Emini, Emilio A; Scott, Daniel A
Given the concurrent administration of multiple vaccines during routine pediatric immunizations, efforts to elucidate the potential interference of any vaccine on the immune response to the concomitantly administered antigens are fundamental to prelicensure clinical research. This phase 3 randomized controlled trial of 13-valent pneumococcal conjugate vaccine (PCV13) versus 7-valent PCV (PCV7) assessed immune responses of concomitantly administered meningococcal group C conjugated to diphtheria toxin cross-reactive material 197 (MnCCV-CRM197) in a 2-dose infant series and 15-month toddler dose. 619 subjects were randomized, 315 to PCV13 and 304 to PCV7. MnCCV-CRM197-induced immune responses were similar between the PCV13 and PCV7 groups, with >97% of the subjects achieving a ≥1:8 meningococcal serum bactericidal assay (SBA) titer after both dose 2 and the toddler dose. Geometric mean titers were lower in the PCV13 group 191.22 (167.72, 218.02) versus 266.19 (234.86, 301.71) following dose 2 and 432.28 (361.22, 517.31) versus 730.84 (642.05, 831.91) following the toddler dose. The geometric mean (GM) meningococcal SBA titer ratios (PCV13/PCV7) were 0.72 after dose 2 and 0.59 after the toddler dose. The criteria for MnCCV-CRM197 non-inferiority for GM titers were satisfied after dose 2. Percent responders was similar up to titers of 1:128. PCV13 elicited substantial antipneumococcal responses against all 13 serotypes, with ≥90% of the subjects achieving an antibody concentration ≥0.35μg/mL after dose 3 in the infant series. Safety and tolerability were similar between the vaccine groups. Immunogenicity results of MnCCV-CRM197 for PCV13 compared with PCV7 included lower GMTs, but the clinical significance of this is unknown as the proportion of infants achieving protective MenC antibody titers was comparable in the two groups. Percent responders were similar up to titers of 1:128. PCV13 has an acceptable safety profile in infants and toddlers, while providing
Lo, Nathan C; Gupta, Ribhav; Stanaway, Jeffrey D; Garrett, Denise O; Bogoch, Isaac I; Luby, Stephen P; Andrews, Jason R
Typhoid fever remains a major public health problem globally. While new Vi conjugate vaccines hold promise for averting disease, the optimal programmatic delivery remains unclear. We aimed to identify the strategies and associated epidemiologic conditions under which Vi conjugate vaccines would be cost-effective. We developed a dynamic, age-structured transmission and cost-effectiveness model that simulated multiple vaccination strategies with a typhoid Vi conjugate vaccine from a societal perspective. We simulated 10-year vaccination programs with (1) routine immunization of infants (aged typhoid fever and defined strategies as highly cost-effective by using the definition of a low-income country (defined as a country with a gross domestic product of $1045 per capita). We defined incidence as the true number of clinically symptomatic people in the population per year. Vi conjugate typhoid vaccines were highly cost-effective when administered by routine immunization activities through the EPI in settings with an annual incidence of >50 cases/100000 (95% uncertainty interval, 40-75 cases) and when administered through the EPI plus a catch-up campaign in settings with an annual incidence of >130 cases/100000 (95% uncertainty interval, 50-395 cases). The incidence threshold was sensitive to the typhoid-related case-fatality rate, carrier contribution to transmission, vaccine characteristics, and country-specific economic threshold for cost-effectiveness. Typhoid Vi conjugate vaccines would be highly cost-effective in low-income countries in settings of moderate typhoid incidence (50 cases/100000 annually). These results were sensitive to case-fatality rates, underscoring the need to consider factors contributing to typhoid mortality (eg, healthcare access and antimicrobial resistance) in the global vaccination strategy. © The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America.
Evaluation of components of X-ray irradiated 7-valent pneumococcal conjugate vaccine and pneumococcal vaccine polyvalent and X-ray and gamma-ray irradiated acellular pertussis component of DTaP vaccine products
May, J.C.; Rey, L.; Lee, C.-J.; Arciniega, Juan
Samples of pneumococcal vaccine polyvalent, 7-valent pneumococcal conjugate vaccine, and two different diphtheria and tetanus toxoids and acellular pertussis vaccines adsorbed were irradiated with X-rays and/or gamma-rays (Co-60). Mouse IgG and IgM antibody responses (ELISA) for types 9V, 14, 18C, and 19F pneumococcal polysaccharides and conjugates indicated that the polysaccharides were more tolerant of the radiation than the conjugates. The mouse antibody response for the detoxified pertussis toxin (PT) antigen, filamentous hemagglutinin antigen (FHA), pertactin (PRN), and fimbriae types 2 and 3 (FIM) antigens for the appropriate vaccine type indicated that the antibody response was not significantly changed in the 25 kGy X-ray irradiated vaccines frozen in liquid nitrogen compared to the control vaccine
Evaluation of components of X-ray irradiated 7-valent pneumococcal conjugate vaccine and pneumococcal vaccine polyvalent and X-ray and gamma-ray irradiated acellular pertussis component of DTaP vaccine products
May, J.C. E-mail: email@example.com; Rey, L. E-mail: firstname.lastname@example.org; Lee, C.-J.; Arciniega, Juan
Samples of pneumococcal vaccine polyvalent, 7-valent pneumococcal conjugate vaccine, and two different diphtheria and tetanus toxoids and acellular pertussis vaccines adsorbed were irradiated with X-rays and/or gamma-rays (Co-60). Mouse IgG and IgM antibody responses (ELISA) for types 9V, 14, 18C, and 19F pneumococcal polysaccharides and conjugates indicated that the polysaccharides were more tolerant of the radiation than the conjugates. The mouse antibody response for the detoxified pertussis toxin (PT) antigen, filamentous hemagglutinin antigen (FHA), pertactin (PRN), and fimbriae types 2 and 3 (FIM) antigens for the appropriate vaccine type indicated that the antibody response was not significantly changed in the 25 kGy X-ray irradiated vaccines frozen in liquid nitrogen compared to the control vaccine.
A. V. Rudakova
Full Text Available Aim: cost-effectiveness assessment and budget impact analysis for 13-valent pneumococcal conjugate vaccine (PCV13 in infant immunization program in Russian Federation. Materials and methods: 10 year modeling with social perspective (direct medical and indirect costs and life expectancy with discounting by 3,5% per year and population effect based on results of clinical studies, global PCV13 use and Russian epidemiological data has been established. Budget impact has been analyzed without discounting. Direct effect was assessed by influence on pneumococcal meningitis, bacteremia, pneumonia and acute otitis media (AOM incidence, population effect — by pneumococcal meningitis and hospitalized all-cause pneumonia incidence. Results: Possible PCV13 effectiveness was estimated as 76,6% for invasive pneumococcal diseases (IPD and 23,7% for hospitalized cases of AOM. Vaccination (per 100 000 vaccinated infants can prevent 13,8 lethal cases in vaccinated population and 171,1 — in unvaccinated population. Cost-effectiveness ratio for PCV13 is estimated as 32,400 rubles / LYG and 32,400 rubles / QALY. Cost of 1 lethal case prevention is 140 100 rubles, additional cost for 10 years is 111,5 rubles per child. Conclusions: PCV13 mass vaccination of infants in Russian Federation is highly cost-effective and will significantly cut expenses due to pneumococcal diseases treatment.
Full Text Available Abstract Background Streptococcus pneumoniae infections, which place a considerable burden on healthcare resources, can be reduced in a cost-effective manner using a 7-valent pneumococcal conjugate vaccine (PCV-7. We compare the cost effectiveness of a 13-valent PCV (PCV-13 and a 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV with that of PCV-7 in Turkey. Methods A cost-utility analysis was conducted and a decision analytical model was used to estimate the proportion of the Turkish population Results PCV-13 and PHiD-CV are projected to have a substantial impact on pneumococcal disease in Turkey versus PCV-7, with 2,223 and 3,156 quality-adjusted life years (QALYs and 2,146 and 2,081 life years, respectively, being saved under a 3+1 schedule. Projections of direct medical costs showed that a PHiD-CV vaccination programme would provide the greatest cost savings, offering additional savings of US$11,718,813 versus PCV-7 and US$8,235,010 versus PCV-13. Probabilistic sensitivity analysis showed that PHiD-CV dominated PCV-13 in terms of QALYs gained and cost savings in 58.3% of simulations. Conclusion Under the modeled conditions, PHiD-CV would provide the most cost-effective intervention for reducing pneumococcal disease in Turkish children.
Dagna O. Constenla
Full Text Available OBJECTIVE:A decision-analytic model was constructed to evaluate the economic impact of post-introduction pneumococcal conjugate vaccine (PCV programs in Ecuador, Honduras, and Paraguay from the societal perspective. METHODS: Hypothetical birth cohorts were followed for a 20-year period in each country. Estimates of disease burden, vaccine effectiveness, and health care costs were derived from primary and secondary data sources. Costs were expressed in 2014 US$. Sensitivity analyses were performed to assess the impact of model input uncertainties. RESULTS: Over the 20 years of vaccine program implementation, the health care costs per case ranged from US$ 764 854 to more than US$ 1 million. Vaccination prevented more than 50% of pneumococcal cases and deaths per country. At a cost of US$ 16 per dose, the cost per disability-adjusted life year (DALY averted for the 10-valent PCV (PCV10 and the 13-valet PCV (PCV13 ranged from US$ 796 (Honduras to US$ 1 340 (Ecuador and from US$ 691 (Honduras to US$ 1 166 (Ecuador respectively. At a reduced price (US$ 7 per dose, the cost per DALY averted ranged from US$ 327 (Honduras to US$ 528 (Ecuador and from US$ 281 (Honduras to US$ 456 (Ecuador for PCV10 and PCV13 respectively. Several model parameters influenced the results of the analysis, including vaccine price, vaccine efficacy, disease incidence, and costs. CONCLUSIONS: The economic impact of post-introduction PCV needs to be assessed in a context of uncertainty regarding changing antibiotic resistance, herd and serotype replacement effects, differential vaccine prices, and government budget constraints.
Constenla, Dagna O
A decision-analytic model was constructed to evaluate the economic impact of post-introduction pneumococcal conjugate vaccine (PCV) programs in Ecuador, Honduras, and Paraguay from the societal perspective. Hypothetical birth cohorts were followed for a 20-year period in each country. Estimates of disease burden, vaccine effectiveness, and health care costs were derived from primary and secondary data sources. Costs were expressed in 2014 US$. Sensitivity analyses were performed to assess the impact of model input uncertainties. Over the 20 years of vaccine program implementation, the health care costs per case ranged from US$ 764 854 to more than US$ 1 million. Vaccination prevented more than 50% of pneumococcal cases and deaths per country. At a cost of US$ 16 per dose, the cost per disability-adjusted life year (DALY) averted for the 10-valent PCV (PCV10) and the 13-valet PCV (PCV13) ranged from US$ 796 (Honduras) to US$ 1 340 (Ecuador) and from US$ 691 (Honduras) to US$ 1 166 (Ecuador) respectively. At a reduced price (US$ 7 per dose), the cost per DALY averted ranged from US$ 327 (Honduras) to US$ 528 (Ecuador) and from US$ 281 (Honduras) to US$ 456 (Ecuador) for PCV10 and PCV13 respectively. Several model parameters influenced the results of the analysis, including vaccine price, vaccine efficacy, disease incidence, and costs. The economic impact of post-introduction PCV needs to be assessed in a context of uncertainty regarding changing antibiotic resistance, herd and serotype replacement effects, differential vaccine prices, and government budget constraints.
Che, Datian; Zhou, Hua; He, Jinchun; Wu, Bin
The purpose of this study was to compare, from a Chinese societal perspective, the projected health benefits, costs, and cost-effectiveness of adding pneumococcal conjugate heptavalent vaccine (PCV-7) to the routine compulsory child immunization schedule. A decision-tree model, with data and assumptions adapted for relevance to China, was developed to project the health outcomes of PCV-7 vaccination (compared with no vaccination) over a 5-year period as well as a lifetime. The vaccinated birth cohort included 16,000,000 children in China. A 2 + 1 dose schedule at US$136.51 per vaccine dose was used in the base-case analysis. One-way sensitivity analysis was used to test the robustness of the model. The impact of a net indirect effect (herd immunity) was evaluated. Outcomes are presented in terms of the saved disease burden, costs, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio. In a Chinese birth cohort, a PCV-7 vaccination program would reduce the number of pneumococcus-related infections by at least 32% and would prevent 2,682 deaths in the first 5 years of life, saving $1,190 million in total costs and gaining an additional 9,895 QALYs (discounted by 3%). The incremental cost per QALY was estimated to be $530,354. When herd immunity was taken into account, the cost per QALY was estimated to be $95,319. The robustness of the model was influenced mainly by the PCV-7 cost per dose, effectiveness herd immunity and incidence of pneumococcal diseases. With and without herd immunity, the break-even costs in China were $29.05 and $25.87, respectively. Compulsory routine infant vaccination with PCV-7 is projected to substantially reduce pneumococcal disease morbidity, mortality, and related costs in China. However, a universal vaccination program with PCV-7 is not cost-effective at the willingness-to-pay threshold that is currently recommended for China by the World Health Organization.
Giglio, Norberto D; Cane, Alejandro D; Micone, Paula; Gentile, Angela
Due to the region's own conditions, universal vaccination with pneumococcal conjugate heptavalent vaccine (PCV-7) in Latin American countries is still controversial. To compare projected economic costs and health benefits associated with pneumococcal conjugate heptavalent vaccine as a routine immunization in healthy children in Argentina. A decision analytic model of Markov simulated lifetime evolution of a birth cohort (n 696,451) was developed and compared costs and health benefits of pneumococcal disease in the presence and absence of vaccination. Cost per life year (LY) gained, reduce in diseases burden and costs of vaccination. From the society's perspective, the incremental cost per LY gained was US$ 5599.42 and the purchase of the 4 doses of vaccine for the entire cohort with a cost of US$ 26.5 dose requires an investment of US$ 73,823,806.00. The model estimated that vaccination reduce the number of death by 159 cases of meningitis, 756 cases of bacteriemias 4594 cases of pneumonias about 84,769 cases of otitis media and 20 meningitis sequelae. The value of the cost per LY gained was considerably modified by the variation in the cost of the vaccine dose, efficacy/effectiveness of the vaccine for pneumonia the mortality from pneumonia and herd immunity. Our analysis predicted that routine vaccination of healthy infants <2 years could prevent an important number of pneumococcal infectious and reduce related mortality and morbidity. This strategic could be highly cost-effective in Argentina. Copyright 2010 Elsevier Ltd. All rights reserved.
Mogasale, Vittal; Ramani, Enusa; Park, Il Yeon; Lee, Jung Seok
A Typhoid Conjugate Vaccine (TCV) is expected to acquire WHO prequalification soon, which will pave the way for its use in many low- and middle-income countries where typhoid fever is endemic. Thus it is critical to forecast future vaccine demand to ensure supply meets demand, and to facilitate vaccine policy and introduction planning. We forecasted introduction dates for countries based on specific criteria and estimated vaccine demand by year for defined vaccination strategies in 2 scenarios: rapid vaccine introduction and slow vaccine introduction. In the rapid introduction scenario, we forecasted 17 countries and India introducing TCV in the first 5 y of the vaccine's availability while in the slow introduction scenario we forecasted 4 countries and India introducing TCV in the same time period. If the vaccine is targeting infants in high-risk populations as a routine single dose, the vaccine demand peaks around 40 million doses per year under the rapid introduction scenario. Similarly, if the vaccine is targeting infants in the general population as a routine single dose, the vaccine demand increases to 160 million doses per year under the rapid introduction scenario. The demand forecast projected here is an upper bound estimate of vaccine demand, where actual demand depends on various factors such as country priorities, actual vaccine introduction, vaccination strategies, Gavi financing, costs, and overall product profile. Considering the potential role of TCV in typhoid control globally; manufacturers, policymakers, donors and financing bodies should work together to ensure vaccine access through sufficient production capacity, early WHO prequalification of the vaccine, continued Gavi financing and supportive policy.
Maricruz Gutiérrez Brito
Full Text Available OBJECTIVE: To assess the safety and immune responses induced by a 13-valent pneumococcal conjugate vaccine (PCV13 after immunization of infants in Mexico. METHODS: PCV13 was given with other routine childhood vaccinations to 225 infants in Mexico at ages 2, 4, 6, and 12 months. RESULTS: The proportions of subjects achieving immunoglobulin G (IgG concentrations ≥0.35 µg/mL after the infant series and toddler dose were ≥93.1% and ≥96.7%, respectively, for all 13 serotypes. The serotype-specific pneumococcal IgG geometric mean concentrations after the infant series and toddler dose ranged from 1.18 to 9.13 µg/mL and from 1.62 to 15.41 µg/mL, respectively. The most common local reaction and systemic event after each dose were tenderness and irritability, respectively. Most fever was mild; no fever >40.0°C (i.e., severe was reported. One subject withdrew because of Kawasaki disease 5 days after the first dose of vaccines, but this condition was not considered related to PCV13. CONCLUSIONS: Overall, PCV13 administered with routine pediatric vaccines was immunogenic and safe in healthy infants in Mexico.
Qian, Feng; Wu, Yimin; Muratova, Olga; Zhou, Hong; Dobrescu, Gelu; Duggan, Peter; Lynn, Lambert; Song, Guanhong; Zhang, Yanling; Reiter, Karine; MacDonald, Nicholas; Narum, David L; Long, Carole A; Miller, Louis H; Saul, Allan; Mullen, Gregory E D
Conjugation of polysaccharides to carrier proteins has been a successful approach for producing safe and effective vaccines. In an attempt to increase the immunogenicity of two malarial vaccine candidate proteins of Plasmodium falciparum, apical membrane antigen 1 (AMA1) to a blood stage vaccine candidate and surface protein 25 (Pfs25) a mosquito stage vaccine candidate, were each independently chemically conjugated to the mutant, nontoxic Pseudomonas aeruginosa ExoProtein A (rEPA). AMA1 is a large (66kD) relatively good immunogen in mice; Pfs25 is a poorly immunogenic protein when presented on alum to mice. Mice were immunized on days 0 and 28 with AMA1- or Pfs25-rEPA conjugates or unconjugated AMA1 or Pfs25, all formulated on Alhydrogel. Remarkably, sera from mice 14 days after the second immunization with Pfs25-rEPA conjugates displayed over a 1000-fold higher antibody titers as compared to unconjugated Pfs25. In contrast, AMA1 conjugated under the same conditions induced only a three-fold increase in antibody titers. When tested for functional activity, antibodies elicited by the AMA1-rEPA inhibited invasion of erythrocytes by blood-stage parasites and antibodies elicited by the Pfs25-rEPA conjugates blocked the development of the sexual stage parasites in the mosquito midgut. These results demonstrate that conjugation to rEPA induces a marked improvement in the antibody titer in mice for the poor immunogen (Pfs25) and for the larger protein (AMA1). These conjugates now need to be tested in humans to determine if mice are predictive of the response in humans.
Arutla, Viswanath; Leal, Joseph; Liu, Xiaowei; Sokalingam, Sriram; Raleigh, Michael; Adaralegbe, Adejimi; Liu, Li; Pentel, Paul R; Hecht, Sidney M; Chang, Yung
Since the demonstration of nicotine vaccines as a possible therapeutic intervention for the effects of tobacco smoke, extensive effort has been made to enhance nicotine specific immunity. Linker modifications of nicotine haptens have been a focal point for improving the immunogenicity of nicotine, in which the evaluation of these modifications usually relies on in vivo animal models, such as mice, rats or nonhuman primates. Here, we present two in vitro screening strategies to estimate and predict the immunogenic potential of our newly designed nicotine haptens. One utilizes a competition enzyme-linked immunoabsorbent assay (ELISA) to profile the interactions of nicotine haptens or hapten-protein conjugates with nicotine specific antibodies, both polyclonal and monoclonal. Another relies on computational modeling of the interactions between haptens and amino acid residues near the conjugation site of the carrier protein to infer linker-carrier protein conjugation effect on antinicotine antibody response. Using these two in vitro methods, we ranked the haptens with different linkers for their potential as viable vaccine candidates. The ELISA-based hapten ranking was in an agreement with the results obtained by in vivo nicotine pharmacokinetic analysis. A correlation was found between the average binding affinity (IC 50 ) of the haptens to an anti-Nic monoclonal antibody and the average brain nicotine concentration in the immunized mice. The computational modeling of hapten and carrier protein interactions helps exclude conjugates with strong linker-carrier conjugation effects and low in vivo efficacy. The simplicity of these in vitro screening strategies should facilitate the selection and development of more effective nicotine conjugate vaccines. In addition, these data highlight a previously under-appreciated contribution of linkers and hapten-protein conjugations to conjugate vaccine immunogenicity by virtue of their inclusion in the epitope that binds and
Sundaram, Neisha; Chen, Cynthia; Yoong, Joanne; Luvsan, Munkh-Erdene; Fox, Kimberley; Sarankhuu, Amarzaya; La Vincente, Sophie; Jit, Mark
The Ministry of Health (MOH), Mongolia, is considering introducing 13-valent pneumococcal conjugate vaccine (PCV13) in its national immunization programme to prevent the burden of disease caused by Streptococcus pneumoniae. This study evaluates the cost-effectiveness and budget impact of introducing PCV13 compared to no PCV vaccination in Mongolia. The incremental cost-effectiveness ratio (ICER) of introducing PCV13 compared to no PCV vaccination was assessed using an age-stratified static multiple cohort model. The risk of various clinical presentations of pneumococcal disease (meningitis, pneumonia, non-meningitis non-pneumonia invasive pneumococcal disease and acute otitis media) at all ages for thirty birth cohorts was assessed. The analysis considered both health system and societal perspectives. A 3+0 vaccine schedule and price of US$3.30 per dose was assumed for the baseline scenario based on Gavi, the Vaccine Alliance's advance market commitment tail price. The ICER of PCV13 introduction is estimated at US$52 per disability-adjusted life year (DALY) averted (health system perspective), and cost-saving (societal perspective). Although indirect effects of PCV have been well-documented, a conservative scenario that does not consider indirect effects estimated PCV13 introduction to cost US$79 per DALY averted (health system perspective), and US$19 per DALY averted (societal perspective). Vaccination with PCV13 is expected to cost around US$920,000 in 2016, and thereafter US$820,000 every year. The programme is likely to reduce direct disease-related costs to MOH by US$440,000 in the first year, increasing to US$510,000 by 2025. Introducing PCV13 as part of Mongolia's national programme appears to be highly cost-effective when compared to no vaccination and cost-saving from a societal perspective at vaccine purchase prices offered through Gavi. Notwithstanding uncertainties around some parameters, cost-effectiveness of PCV introduction for Mongolia remains
... very sick. It causes blood infections, pneumonia, and meningitis, mostly in young children. (Meningitis... have many causes, and PCV13 only works against the types of pneumococcal bacteria targeted by the... the parent or legal representative in the case of a child) receiving vaccines covered under the...
Peter Klein Klouwenberg
Full Text Available Encapsulated bacteria are responsible for the majority of mortality among neonates and infants. The major components on the surface of these bacteria are polysaccharides which are important virulence factors. Immunity against these components protects against disease. However, most of the polysaccharides are thymus-independent (TI-2 antigens which induce an inadequate immune response in neonates and infants. The mechanisms that are thought to play a role in the unresponsiveness of this age group to TI-2 stimuli will be discussed. The lack of immune response may be overcome by conjugating the polysaccharides to a carrier protein. This transforms bacterial polysaccharides from a TI-2 antigen into a thymus-dependent (TD antigen, thereby inducing an immune response and immunological memory in neonates and infants. Such conjugated vaccines have been shown to be effective against the most common causes of invasive disease caused by encapsulated bacteria in neonates and children. These and several other approaches in current vaccine development will be discussed.
Kim, John S; Laskowich, Erin R; Arumugham, Rasappa G; Kaiser, Raymond E; MacMichael, Gregory J
A simple and sensitive gas chromatographic method was designed for quantitative analysis of Streptococcus pneumoniae capsular polysaccharides, activated polysaccharides, and polysaccharide conjugates. Pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F polysaccharide or conjugate were subjected to methanolysis in 3N hydrochloric acid in methanol followed by re-N-acetylation and trimethylsilylation. Derivatized samples were chromatographed and detected using gas chromatography with mass selective detector. Gas chromatographic results were compared with colorimetric values with agreement of 92 to 123% over the range of all samples tested. Monosaccharides released during methanolysis included hexoses, uronic acids, 6-deoxy-hexoses, amino sugars, and alditols. Quantitative recovery of monosaccharides was achieved for all serotypes by the use of a single methanolysis, derivatization, and chromatography procedure. Response factors generated from authentic monosaccharide standards were used for quantitation of pneumococcal polysaccharides and conjugates with confirmation of peak assignments by retention time and mass spectral analysis. This method allows saccharide quantitation in multivalent pneumococcal vaccine intermediates and final drug products with low-level detection (10 pg) and peak purity.
Kantsø, Bjørn; Halkjær, Sofie Ingdam; Thomsen, Ole Østergaard
BACKGROUND: Patients with Crohn's disease (CD) have a higher risk of infectious diseases including pneumococcal infections, and the risk increases with immunotherapy. The primary endpoint of this study was to investigate the specific antibody response to two pneumococcal vaccines in CD patients...... with and without immunosuppressive treatment four weeks post vaccination. METHODS: In a randomized trial of the 23-valent pneumococcal polysaccharide vaccine (PPV23) and the 13-valent pneumococcal conjugated vaccine (PCV13), a group of CD patients treated with immunosuppressive drugs (IS) alone or in combination...... with TNF-α antagonists were compared to a group of CD patients not treated with any of these drugs (untreated). Specific pneumococcal antibody concentrations were measured against 12 serotypes common to the two vaccines before and 4 week after vaccination. RESULTS: PCV13 induced a significantly higher...
Nagel, J; Saxne, T; Geborek, P; Bengtsson, A A; Jacobsen, S; Svaerke Joergensen, C; Nilsson, J-Å; Skattum, L; Jönsen, A; Kapetanovic, M C
Background/purpose The objective of this study was to explore the impact of systemic lupus erythematosus and belimumab given in addition to standard of care therapy on 13-valent conjugated pneumococcal vaccine (PCV13) response. Methods Forty-seven systemic lupus erythematosus patients and 21 healthy controls were immunized with a single dose of 13-valent conjugated pneumococcal vaccine. Forty systemic lupus erythematosus patients were treated with traditional disease-modifying anti rheumatic drugs, 11 of those received belimumab in addition, and 32 patients were treated with concomitant prednisolone. Quantification of serotype specific IgG levels to 12 pneumococcal capsular polysaccharides was performed in serum taken before and four to six weeks after vaccination using multiplex fluorescent microsphere immunoassay. IgG levels against serotypes 23F and 6B were also analyzed using standard enzyme-linked immunosorbent assays. Opsonophagocytic assay was performed on serotype 23F to evaluate the functionality of the antibodies. Pre- and post-vaccination log transformed antibody levels were compared to determine the impact of systemic lupus erythematosus diagnosis and different treatments on antibody response. Results Systemic lupus erythematosus patients as a group showed lower post-vaccination antibody levels and lower fold increase of antibody levels after vaccination compared to controls ( p = 0.02 and p = 0.009, respectively). Systemic lupus erythematosus patients treated with belimumab in addition to standard of care therapy or with only hydroxychloroquine did not differ compared to controls, whereas the other treatment groups had significantly lower fold increase of post-vaccination antibody levels. Higher age was associated with lower post-vaccination antibody levels among systemic lupus erythematosus patients. Conclusion Belimumab given in addition to traditional disease-modifying anti rheumatic drugs or prednisolone did not further impair antibody
Jansen, Angelique G S C; Sanders, Elisabeth A M; Smulders, Sara; Hoes, Arno W; Hak, Eelko
In a randomized double-blind controlled trial, the safety was assessed of simultaneous administration of influenza and pneumococcal conjugate vaccines in children with previous physician-diagnosed respiratory tract infections. In total, 579 children aged 18-72 months were assigned to receive
Full Text Available Following the introduction of 7- and 13-pneumococcal conjugate vaccines (PCVs in Israel, we demonstrated that within Streptococcus pneumoniae (Sp positive middle ear cultures, obtained from young children with severe acute otitis media (AOM episodes, there were more penicillin-susceptible and less multi-drug resistant Sp isolates in PCV immunized children.
Warren, Joshua L.; Shioda, Kayoko; Kürüm, Esra
Background: Pneumococcal conjugate vaccines (PCVs) are being used worldwide. A key question is whether the impact of PCVs on pneumonia is similar in low- and high-income populations. However, most low-income countries, where the burden of disease is greatest, lack reliable data that can be used t...
Wanderci Marys Oliveira Abrão
Full Text Available INTRODUCTION: In 2010, to reduce the occurrence of serious pneumococcal disease, the Ministry of Health in Brazil incorporated the 10-valent pneumococcal vaccine in the immunization schedule of children younger than two years of age. The objective of this study was to evaluate the impact of vaccination on the incidence of infectious respiratory diseases in infants before and after the introduction of the 10-valent pneumococcal vaccine. METHODS: This cross-sectional study involved primary care and hospital networks from a city in Minas Gerais State, Brazil, between 2009 and 2012. RESULTS: A 40% reduction in the prevalence of community-acquired pneumonia (CAP was observed after introducing the pneumococcal conjugate vaccine. Male children were 28% more likely to develop the disease. The prevalence ratio ([PR] = 1.96, 95% CI: 1.52 to 2.53, p < 0.05 suggested that not being vaccinated was associated with the occurrence of pneumonia. The prevalence of CAP was 70% lower (PR 0.30, 95% CI: 0.24 to 0.37, p<0.05 in children vaccinated as recommended compared to children with delayed vaccination, suggesting that the updated vaccine schedule improves protection. CONCLUSIONS: Immunization with the 10-valent pneumococcal vaccine appeared to reduce the number of pneumonia cases in children during the study period. Prospective studies are needed to confirm the efficacy of the vaccine against the occurrence of pneumococcal pneumonia.
Southern, Jo; Borrow, Ray; Andrews, Nick; Morris, Rhonwen; Waight, Pauline; Hudson, Michael; Balmer, Paul; Findlow, Helen; Findlow, Jamie; Miller, Elizabeth
This study investigated the use of two doses of three different meningococcal group C conjugate (MCC) vaccines when given for primary immunization with a seven-valent pneumococcal conjugate vaccine (PCV7) and Pediacel, a combination product containing five acellular pertussis components, diphtheria and tetanus toxoids, Haemophilus influenzae type b (Hib) conjugate, and inactivated-poliovirus vaccine. The immune response after a single dose of MCC is also presented. Infants were randomized to receive two doses of one of the MCC vaccines and PCV7 at 2 and 3 months or at 2 and 4 months of age. Meningococcal group C serum bactericidal antibody (SBA) geometric mean titers, Hib-polyribosylribitol phosphate (PRP) immunoglobulin G (IgG) geometric mean concentrations (GMCs), and diphtheria and tetanus antitoxin GMCs, together with the proportions of infants achieving putative protective levels, were determined. A total of 393 infants were recruited. Following the first dose of NeisVac-C (MCC conjugated to tetanus toxoid), 97% of infants achieved protective levels (SBA titer of >or=8), compared with 80% and 53%, respectively, for Menjugate and Meningitec (both of which are conjugated to CRM(197)). SBA responses to MCC vaccines were not significantly different when administered at 2 and 3 or 2 and 4 months of age. Following two doses of each MCC, 98 to 100% of infants achieved protective levels. Both PRP IgG and tetanus responses were significantly enhanced when Pediacel was coadministered with NeisVac-C. This study demonstrates that NeisVac-C and Menjugate generate good immunogenicity after the first dose at 2 months of age when coadministered with PCV7 and Pediacel and merit further investigation in single-dose priming strategies.
Safety of Combination of a Tetravalent Meningococcal Conjugate Vaccine Against Serogroups A, C, Y, W-135 With Other Vaccine Preparations: a Prospective Study of a Series of Cases Among Healthy Children and Children With Various Health Abnormalities
Leyla S. Namazova-Baranova
Full Text Available Meningococcal infection is an acute disease caused by Neisseria meningitidis, which proceeds with a diverse clinical aspect from nasopharyngitis to meningococcal meningitis and meningococcemia. Since 2014, a tetravalent meningococcal conjugate vaccine has been registered in Russia. This vaccine creates protection against serogroups A, C, W-135, Y and can be used from the age of nine months to 55 years. The actual issue is a vaccine tolerability, including when combined with other vaccine preparations.Objective: Our aim was to evaluate the safety of a tetravalent meningococcal conjugate vaccine against serogroups A, C, Y and W-135 when it is combined with other vaccine preparations.Methods. A prospective full-design study assessed the tolerability of immunization with a meningococcal conjugate vaccine, both in case of monovaccination and in combination with a pneumococcal 13-valent conjugate vaccine, measles-mumps-rubella, viral hepatitis A, influenza, and chicken pox vaccines.Results. 97 children aged from 9 months to 18 years were vaccinated, 20 of them were healthy and 77 had medical issues (with allergic pathology, ENT diseases, cardiovascular and nervous system diseases, lung diseases as well as orphan diseases. Among vaccinated children, general reactions were observed in 3/97 (3.1% children, local reactions — in 5 (5.2%. The post-vaccination period passed asymptomatically and uneventfully in the prevailing majority of children vaccinated with a tetravalent meningococcal conjugate vaccine (in 91, 93.8%.Conclusion. The immunization with a tetravalent meningococcal conjugate vaccine against serogroups A, C, Y, W-135 is well tolerated, both in case of monovaccination and in combination with other vaccine preparations, in healthy children of different age groups and in patients with different health status.
Straetemans, M.; Palmu, A.; Auranen, K.; Zielhuis, G.A.; Kilpi, T.
OBJECTIVE: To explore the effect of a pneumococcal conjugate vaccine on the risk of otitis media with effusion and to search for subgroups in which the vaccine had a higher or lower effect. METHODS: Analyses were performed on data from the Finnish Otitis Media Vaccine Trial, a randomised controlled
Sinha, Anushua; Levine, Orin; Knoll, Maria D; Muhib, Farzana; Lieu, Tracy A
Routine vaccination of infants against Streptococcus pneumoniae (pneumococcus) needs substantial investment by governments and charitable organisations. Policymakers need information about the projected health benefits, costs, and cost-effectiveness of vaccination when considering these investments. Our aim was to incorporate these data into an economic analysis of pneumococcal vaccination of infants in countries eligible for financial support from the Global Alliance for Vaccines & Immunization (GAVI). We constructed a decision analysis model to compare pneumococcal vaccination of infants aged 6, 10, and 14 weeks with no vaccination in the 72 countries that were eligible as of 2005. We used published and unpublished data to estimate child mortality, effectiveness of pneumococcal conjugate vaccine, and immunisation rates. Pneumococcal vaccination at the rate of diptheria-tetanus-pertussis vaccine coverage was projected to prevent 262,000 deaths per year (7%) in children aged 3-29 months in the 72 developing countries studied, thus averting 8.34 million disability-adjusted life years (DALYs) yearly. If every child could be reached, up to 407,000 deaths per year would be prevented. At a vaccine cost of International 5 dollars per dose, vaccination would have a net cost of 838 million dollars, a cost of 100 dollars per DALY averted. Vaccination at this price was projected to be highly cost-effective in 68 of 72 countries when each country's per head gross domestic product per DALY averted was used as a benchmark. At a vaccine cost of between 1 dollar and 5 dollars per dose, purchase and accelerated uptake of pneumococcal vaccine in the world's poorest countries is projected to substantially reduce childhood mortality and to be highly cost-effective.
Pumarola, Felix; Salamanca de la Cueva, Ignacio; Sistiaga-Hernando, Alessandra; García-Corbeira, Pilar; Moraga-Llop, Fernando A; Cardelús, Sara; McCoig, Cynthia; Gómez Martínez, Justo Ramón; Rosell Ferrer, Rosa; Iniesta Turpin, Jesús; Devadiga, Raghavendra
Acute otitis media (AOM) is common in children aged <3 years. A pneumococcal conjugate vaccine (PCV) (PCV7; Prevenar, Pfizer/Wyeth, USA) has been available in Spain since 2001, which has a coverage rate of 50-60% in children aged <5 years. Children aged ≥3 to 36 months with AOM confirmed by an ear-nose-throat specialist were enrolled at seven centers in Spain (February 2009-May 2012) (GSK study identifier: 111425). Middle-ear-fluid samples were collected by tympanocentesis or spontaneous otorrhea and cultured for bacterial identification. Culture-negative samples were further analyzed using polymerase chain reaction (PCR). Of 125 confirmed AOM episodes in 124 children, 117 were analyzed (median age: 17 months (range: 3-35); eight AOM episodes were excluded from analyses. Overall, 69% (81/117) episodes were combined culture- and PCR-positive for ≥1 bacterial pathogen; 44% (52/117) and 39% (46/117) were positive for Haemophilus influenzae (Hi) and Streptococcus pneumoniae (Spn), respectively. 77 of 117 episodes were cultured for ≥1 bacteria, of which 63 were culture-positive; most commonly Spn (24/77; 31%) and Hi (32/77; 42%). PCR on culture-negative episodes identified 48% Hi- and 55% Spn-positive episodes. The most common Spn serotype was 19F (4/24; 17%) followed by 19A (3/24; 13%); all Hi-positive episodes were non-typeable (NTHi). 81/117 AOM episodes (69%) occurred in children who had received ≥1 pneumococcal vaccine dose. NTHi and Spn were the main etiological agents for AOM in Spain. Impact of pneumococcal vaccination on AOM requires further evaluation in Spain, after higher vaccination coverage rate is reached. Copyright © 2015 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.
Chaiyakunapruk, Nathorn; Somkrua, Ratchadaporn; Hutubessy, Raymond; Henao, Ana Maria; Hombach, Joachim; Melegaro, Alessia; Edmunds, John W; Beutels, Philippe
Several decision support tools have been developed to aid policymaking regarding the adoption of pneumococcal conjugate vaccine (PCV) into national pediatric immunization programs. The lack of critical appraisal of these tools makes it difficult for decision makers to understand and choose between them. With the aim to guide policymakers on their optimal use, we compared publicly available decision-making tools in relation to their methods, influential parameters and results. The World Health Organization (WHO) requested access to several publicly available cost-effectiveness (CE) tools for PCV from both public and private provenance. All tools were critically assessed according to the WHO's guide for economic evaluations of immunization programs. Key attributes and characteristics were compared and a series of sensitivity analyses was performed to determine the main drivers of the results. The results were compared based on a standardized set of input parameters and assumptions. Three cost-effectiveness modeling tools were provided, including two cohort-based (Pan-American Health Organization (PAHO) ProVac Initiative TriVac, and PneumoADIP) and one population-based model (GlaxoSmithKline's SUPREMES). They all compared the introduction of PCV into national pediatric immunization program with no PCV use. The models were different in terms of model attributes, structure, and data requirement, but captured a similar range of diseases. Herd effects were estimated using different approaches in each model. The main driving parameters were vaccine efficacy against pneumococcal pneumonia, vaccine price, vaccine coverage, serotype coverage and disease burden. With a standardized set of input parameters developed for cohort modeling, TriVac and PneumoADIP produced similar incremental costs and health outcomes, and incremental cost-effectiveness ratios. Vaccine cost (dose price and number of doses), vaccine efficacy and epidemiology of critical endpoint (for example
Vesikari, Timo; Borrow, Ray; Da Costa, Xavier; Richard, Patrick; Eymin, Cécile; Boisnard, Florence; Lockhart, Stephen
DTaP-IPV-HB-PRP-T or hexavalent vaccines are indicated for primary and booster vaccination of infants and toddlers against diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and invasive diseases caused by Haemophilus influenzae type b (Hib). The present study evaluates the safety and immunogenicity of a ready-to-use hexavalent vaccine when co-administered with a meningococcal serogroup C conjugate (MenC) vaccine in infants. This was a phase III, open-label, randomised, multicentre study conducted in Finland. Healthy infants, aged 46-74days (n=350), were randomised in a ratio of 1:1 to receive DTaP-IPV-HB-PRP-T vaccine at two, three and four months, either with a MenC vaccine co-administered at two and four months (Group 1; n=175) or without MenC vaccine (Group 2; n=175). All infants also received routine rotavirus and 13-valent pneumococcal conjugate vaccines. The proportion of participants with an anti-HBs concentration ⩾10mIU/mL assessed one month after the third dose of DTaP-IPV-HB-PRP-T vaccine was 97.5% [95%CI: 93.1-99.3] in the coadministration group and 96.1% [95%CI: 91.8-98.6] in the group without MenC vaccine. The proportion of participants with an anti-MenC SBA titre ⩾8 assessed one month after the second dose of MenC vaccine was 100% in the coadministration group. Both primary objectives were achieved. Secondary immunogenicity and safety analyses showed that co-administration of DTaP-IPV-HB-PRP-T and MenC vaccines did not impact the immune response to the antigens of each of the two vaccines. All vaccines were well tolerated and the safety profile of DTaP-IPV-HB-PRP-T vaccine was similar in both groups. ClinicalTrials.gov identifier: NCT01839175; EudraCT number: 2012-005547-24. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.
Laursen, B B; Danstrup, C S; Hoffmann, S; Nørskov-Lauritsen, N; Christensen, A L B; Ovesen, T
The objectives of this study were to investigate the incidence of complicated acute otitis media (cAOM) as well as the associated microbiology before and after introduction of the 7- and 13-valent pneumococcal conjugate vaccines (PCV-7 and -13), respectively. CAOM comprises "heavy" AOM (AOM demanding hospitalization), mastodismus (M) and acute mastoiditis (AM). A retrospective cohort study of the incidence and microbiology associated with cAOM during the non-PCV era, the PCV-7 and 13 eras, respectively. Clinical and microbiological data were prospectively registered in a local database. The incidences of cAOM as well as the distribution of various bacterial strains in the three eras were compared. A total of 246 cases of cAOM (125 in the pre-vaccine period (2001-2006), 50 in the PCV-7 period (2007-2010) and 71 in the PCV-13 period (2011-2015)) were identified. The incidence of hAOM decreased by 62% in the PCV7-era but increased to almost pre-vaccine levels in the PCV-13 era. In the M + AM group, a decrease by almost 21% in the PCV7-era was found compared to the pre vaccine era, whereas the decrease was only 12% in the PCV13-era. The three most common findings in both hAOM and M + AM were Streptococcus pneumonia (SP), group A streptococcus (GAS) and "no growth". In the hAOM group, SP decreased from 38% in the pre-vaccine era to 31% in the PCV7-era and further to 16% in the PCV13-era. GAS decreased from 17% in the pre-vaccine era to 0% in the PCV7-era and 16% in the PCV13-era. The percentage of "no growth" increased from 12% to 38% and 44%, respectively. In the M + AM group, SP decreased to 10% in the PCV13-era compared with 44% in the pre-vaccine era and 41% in the PCV7-era. An increase in GAS from 15% in the pre-vaccine era and PCV7-era to 30% in the PCV13-era was observed. The "no growth" percentage increased from 13% in the pre-vaccine era to 26% in the PCV7-era and 33% in the PCV13-era. Introduction of PCV7 and PCV13 has been associated with an overall
Invasive pneumococcal disease : Clinical outcomes and patient characteristics 2-6 years after introduction of 7-valent pneumococcal conjugate vaccine compared to the pre-vaccine period, the Netherlands
Wagenvoort, Gertjan H J; Sanders, Elisabeth A M; Vlaminckx, Bart J.; Elberse, Karin E.; de Melker, Hester E.; van der Ende, Arie; Knol, Mirjam J.
Background Implementation of 7-valent pneumococcal conjugate vaccine (PCV7) in the Dutch national immunization program for infants led to a shift from vaccine to non-vaccine serotypes in invasive pneumococcal disease (IPD) in all age groups. We studied the impact of the serotype shift on clinical
Li, KeXin; Chen, DaWei; Zhao, XiuLi; Hu, HaiYang; Yang, ChunRong; Pang, DaHai
We prepared and optimized Ulex europaeus agglutinin I (UEAI)-modified Bovine serum albumin (BSA)-encapsulating liposomes (UEAI-LIP) as oral vaccine carriers and examined the feasibility of inducing systemic and mucosal immune responses by oral administration of UEAILIP. The prepared systems were characterized in vitro for their average size, zeta potential, encapsulation efficiency (EE%) and conjugation efficiency (CE%). In vitro release studies indicated that the presence of UEAI around the optimized liposomes was able to prevent a burst release of loaded BSA and provide sustained release of the encapsulated protein. In vivo immune-stimulating results in KM mice showed that BSA given intramuscularly generated systemic response only but both systemic and mucosal immune responses could be induced simultaneously in the groups in which BSA-loaded liposomes (LIP) and UEAI-LIP were administered intragastrically. Furthermore, the modification of UEAI on the surface of liposomes could further enhance the IgA and IgG levels obviously. In conclusion, this study demonstrated the high potential of lectin-modified liposomes containing the antigen as carriers for oral vaccine.
Suarez, Victor; Michel, Fabiana; Toscano, Cristiana M; Bierrenbach, Ana Luiza; Gonzales, Marco; Alencar, Airlane Pereira; Ruiz Matus, Cuauhtemoc; Andrus, Jon K; de Oliveira, Lucia H
Streptococcus pneumoniae is the leading cause of bacterial pneumonia, meningitis and sepsis in children worldwide. Despite available evidence on pneumococcal conjugate vaccine (PCV) impact on pneumonia hospitalizations in children, studies demonstrating PCV impact in morbidity and mortality in middle-income countries are still scarce. Given the disease burden, PCV7 was introduced in Peru in 2009, and then switched to PCV10 in late 2011. National public healthcare system provides care for 60% of the population, and national hospitalization, outpatient and mortality data are available. We thus aimed to assess the effects of routine PCV vaccination on pneumonia hospitalization and mortality, and acute otitis media (AOM) and all cause pneumonia outpatient visits in children under one year of age in Peru. We conducted a segmented time-series analysis using outcome-specific regression models. Study period was from January 2006 to December 2012. Data sources included the National information systems for hospitalization, mortality, outpatient visits, and RENACE, the national database of aggregated weekly notifications of pneumonia and other acute respiratory diseases (both hospitalized and non-hospitalized). Study outcomes included community acquired pneumonia outpatient visits, hospitalizations and deaths (ICD10 codes J12-J18); and AOM outpatient visits (H65-H67). Monthly age- and sex-specific admission, outpatient visit, and mortality rates per 100,000 children aged Peru. Copyright © 2016. Published by Elsevier Ltd.
Tarek A. Ahmad
Full Text Available Klebsiella pneumoniae is a major cause of nosocomial pneumonia, septicemia and urinary tract infections, especially in newborns, blood cancer patients, and other immunocompromised candidates. The control of K. pneumoniae is a complicated issue due to its tight pathogenesis. Immuno-prophylactic preparations, especially those directed toward the bacterium O-antigen, showed to be the most successful way to prevent the infection incidence. However, all previously proposed preparations were either of limited spectrum or non-maternal, and hence not targeting the main Klebsiella patients. Moreover, all preparations were directed only to prevent the respiratory diseases due to that pathogen. This article addresses the development of a method originally used to purify the non-capsular bacterial- endotoxins, as a new and easy method for vaccine production against K. pneumoniae. The application of this method was preceded by a biotechnological control of capsular polysaccharide production in K. pneumoniae. The new produced natural conjugate between the bacterial O-antigen and its outer membrane proteins was evaluated by physicochemical and immunological methods to investigate its purity, integrity, safety and immunogenicity. It showed to be pure, stable, safe for use, and able to elicit a protective immunoglobulin titer against different Klebsiella infections. This immune-response proved to be transferable to the offspring of the vaccinated experimental rabbits via placenta.
Durando, Paolo; Rosselli, Roberto; Cremonesi, Ilaria; Orsi, Andrea; Albanese, Erika; Barberis, Ilaria; Paganino, Chiara; Trucchi, Cecilia; Martini, Mariano; Marensi, Lorenzo; Turello, Valter; Study Group, the Ligurian Pneumococcal; Bregante, Alessandro; Cacciani, Roberto; Iudici, Rocco; La Marca, Diego; Pedano, Leonardo; Petrucci, Amadio Franco; Santolini, Maria; Sbisà, Valentina; Zacconi, Monica
Background In September 2011 the European Medical Agency authorized the use of 13-valent pneumococcal conjugate vaccine (PCV13) in adults aged ≥50 years. The same occurred in the US in December 2011 when the Food and Drug Administration approved the use of PCV13 in the same target age-group with indication for the prevention of invasive pneumococcal diseases and community acquired pneumonia sustained by the serotypes contained in the vaccine. The Liguria Region, in Italy, implemented in 2013 an active and free of charge immunization strategy with PCV13 among adults affected by specific risk conditions and the elderly aged ≥70 years. Methods An observational study was performed in order to assess the safety and tolerability of PCV13 among elderly dwelling in the metropolitan area of Genoa, the capital city of Liguria Region. Eligible subjects, who received PCV13 following the public health immunization campaign at the Local Health Unit 3 of Genoa, provided a written informed consent to take part in the study. Eight-hundred-seventy-one subjects were enrolled between October 2013 and May 2014: all were monitored by qualified healthcare personnel for at least 30 min after vaccination at the outpatient clinics, in order to assess any possible sudden reaction. The occurrence of a series of local and systemic solicited reactions and of any unsolicited Adverse Events (AEs) was monitored using a self-administered clinical diary and by regular phone contacts up to 14 and 21 d following immunization, respectively. Moreover, a 6-months follow-up following vaccination was planned in order to monitor Severe Adverse Events (SAEs). Results No sudden reaction occurred in vaccinees at the outpatient clinics. Pain (27.4%) was the most frequent reaction reported by subjects at the injection site, while new muscle pain (13.6%), fatigue (10.7%), and headache (9.9%) resulted the most common systemic reactions. Rates of the main reactions reported in this on-field study resulted
Ana Cristina Cisne Frota
Full Text Available Abstract Objective: HIV-infected individuals (HIVI are threatened by meningococcal infection and presented lower response to vaccines. Data are scarce on long-term persistence of human serum bactericidal antibody (hSBA after a meningococcal C conjugate (MCC vaccine in HIVI youth; the authors aimed to describe this persistence in HIVI. Methods: HIVI and HIV uninfected individuals (HIVU, aged 2–18 years, CD4 >15% were recruited. Seroprotection (hSBA ≥1:4 at baseline and at 12–18 months after immunization was evaluated and the association of the different factors with the long-term persistence was calculated using logistic regression. Results: A total of 145 HIVI, 50 HIVU were recruited and immunized, and their median age was 11 years (median age in HIVI group was 12 years, and 10 years in HIVU group, p-value = 0.02. 85 HIVI (44% had undetectable viral load (UVL. Seroprotection rate was 27.2%: 24.1% in HIVI and 36% in HIVU 12–18 months after immunization (p = 0.14. Baseline immunity (odds ratio [OR] = 70.70, 95% CI: 65.2–766.6; UVL at entry (OR: 2.87, 95% CI: 0.96–8.62 and lower family income (OR: 0.09, 95% CI: 0.01–0.69 were associated with seroprotection among HIVI. Conclusion: Seroprotection at 12–18 months after single dose of MCC was low for both groups, and higher among individuals who presented baseline immunity. Among HIVI, vaccine should be administered after UVL is achieved.
Longitudinal multiparameter single-cell analysis of macaques immunized with pneumococcal protein-conjugated or unconjugated polysaccharide vaccines reveals distinct antigen specific memory B cell repertoires.
Full Text Available The efficacy of protein-conjugated pneumococcal polysaccharide vaccines has been well characterized for children. The level of protection conferred by unconjugated polysaccharide vaccines remains less clear, particularly for elderly individuals who have had prior antigenic experience through immunization with unconjugated polysaccharide vaccines or natural exposure to Streptococcus pneumoniae.We compared the magnitude, diversity and genetic biases of antigen-specific memory B cells in two groups of adult cynomolgus macaques that were immunized with a 7-valent conjugated vaccine and boosted after five years with either a 13-valent pneumococcal polysaccharide conjugate vaccine (13vPnC or a 23-valent unconjugated pneumococcal polysaccharide vaccine (23vPS using microengraving (a single-cell analysis method and single-cell RT-PCR.Seven days after boosting, the mean frequency of antigen-specific memory B cells was significantly increased in macaques vaccinated with 13vPnC compared to those receiving 23vPS. The 13vPnC-vaccinated macaques also exhibited a more even distribution of antibody specificities to four polysaccharides in the vaccine (PS4, 6B, 14, 23F that were examined. However, single-cell analysis of the antibody variable region sequences from antigen-specific B cells elicited by unconjugated and conjugated vaccines indicated that both the germline gene segments forming the heavy chains and the average lengths of the Complementary Determining Region 3 (CDR3 were similar.Our results confirm that distinctive differences can manifest between antigen-specific memory B cell repertoires in nonhuman primates immunized with conjugated and unconjugated pneumococcal polysaccharide vaccines. The study also supports the notion that the conjugated vaccines have a favorable profile in terms of both the frequency and breadth of the anamnestic response among antigen-specific memory B cells.
Moreira, Marta; Cintra, Otavio; Harriague, Julie; Hausdorff, William P; Hoet, Bernard
Brazil introduced the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV, Synflorix™, GSK Vaccines) in the routine childhood immunization program in 2010 with a 3+1 schedule (with catch-up for children media. Nasopharyngeal carriage of vaccine-type and any-type pneumococci decreased after the primary doses, with no early signs of replacement with other pathogens. Finally, herd protection against vaccine-type invasive pneumococcal disease and pneumonia in unvaccinated subjects was shown in some studies for some age groups. In conclusion, pneumococcal disease decreased after the introduction of PHiD-CV into the Brazilian national immunization program. Further follow-up is needed to evaluate the long-term overall impact of PHiD-CV in the Brazilian population. Copyright © 2016 GlaxoSmithKline Biologicals SA. Published by Elsevier Ltd.. All rights reserved.
Earnshaw Stephanie R
Full Text Available Abstract Background Thirteen-valent pneumococcal conjugate vaccine (PCV13 and 10-valent pneumococcal conjugate vaccine (PCV10 are two recently approved vaccines for the active immunization against Streptococcus pneumoniae causing invasive pneumococcal disease in infants and children. PCV13 offers broader protection against Streptococcus pneumoniae; however, PCV10 offers potential protection against non-typeable Haemophilus influenza (NTHi. We examined public health and economic impacts of a PCV10 and PCV13 pediatric national immunization programs (NIPs in Canada. Methods A decision-analytic model was developed to examine the costs and outcomes associated with PCV10 and PCV13 pediatric NIPs. The model followed individuals over the remainder of their lifetime. Recent disease incidence, serotype coverage, population data, percent vaccinated, costs, and utilities were obtained from the published literature. Direct and indirect effects were derived from 7-valent pneumococcal vaccine. Additional direct effect of 4% was attributed to PCV10 for moderate to severe acute otitis media to account for potential NTHi benefit. Annual number of disease cases and costs (2010 Canadian dollars were presented. Results In Canada, PCV13 was estimated to prevent more cases of disease (49,340 when considering both direct and indirect effects and 7,466 when considering direct effects only than PCV10. This translated to population gains of 258 to 13,828 more quality-adjusted life-years when vaccinating with PCV13 versus PCV10. Annual direct medical costs (including the cost of vaccination were estimated to be reduced by $5.7 million to $132.8 million when vaccinating with PCV13. Thus, PCV13 dominated PCV10, and sensitivity analyses showed PCV13 to always be dominant or cost-effective versus PCV10. Conclusions Considering the epidemiology of pneumococcal disease in Canada, PCV13 is shown to be a cost-saving immunization program because it provides substantial public
Saez-Llorens, Xavier; Aguilera Vaca, Diana Catalina; Abarca, Katia; Maho, Emmanuelle; Han, Linda; Smolenov, Igor; Dull, Peter
In a primary study, healthy adolescents received 2 doses (months 0/2) of 1 of the 4 investigational meningococcal ABCWY vaccine formulations, containing components of licensed quadrivalent glycoconjugate vaccine MenACWY-CRM, combined with different amounts of recombinant proteins (rMenB) and outer membrane vesicles (OMV) from a licensed serogroup B vaccine, or 2 doses of rMenB alone or 1 dose of MenACWY-CRM then a placebo. This phase 2 extension study evaluated antibody persistence up to 10 months after the 2-dose series and the immunogenicity and safety of a third dose (month 6). Immune responses against serogroups ACWY and serogroup B test strains were measured by serum bactericidal assay with human complement. At month 12, antibody persistence against serogroups ACWY in all 2-dose MenABCWY groups was at least comparable with the 1-dose MenACWY-CRM group. Bactericidal antibodies against most serogroup B test strains declined by month 6, then plateaued over the subsequent 6 months, with overall higher antibody persistence associated with OMV-containing formulations. A third MenABCWY vaccine dose induced robust immune responses against vaccine antigens, although antibody levels 6 months later were comparable with those observed 5 months after the 2-dose series. All investigational MenABCWY vaccines were well tolerated. Two or three doses of investigational MenABCWY vaccines elicited immune responses against serogroups ACWY that were at least comparable with those after 1 dose of MenACWY-CRM. After either vaccination series, investigational MenABCWY vaccine formulations containing OMV had the highest immunogenicity against most serogroup B test strains. No safety concerns were identified in this study.
Sugino, Hirotoshi; Tsumura, Shigeru; Kunimoto, Masaru; Noda, Masuhiro; Chikuie, Daisuke; Noda, Chieko; Yamashita, Mariko; Watanabe, Hiroshi; Ishii, Hidemasa; Tashiro, Toru; Iwata, Kazuhiro; Kono, Takashi; Tsumura, Kaoru; Sumiya, Takahiro; Takeno, Sachio; Hirakawa, Katsuhiro
The Japanese guidelines for acute otitis media in children recommend classifying acute otitis media by age, manifestations and local findings, and also recommend myringotomy for moderate-grade cases with severe local findings, severe-grade cases, and treatment-resistant cases. The heptavalent pneumococcal conjugate vaccine was released in Japan in February 2010. In Hiroshima City, public funding allowing free inoculation with this vaccine was initiated from January 2011, and the number of vaccinated individuals has since increased dramatically. This study investigated changes in the number of myringotomies performed to treat acute otitis media during the 5-year period from January 2008 to December 2012 at two hospitals and five clinics in the Asa Area of Hiroshima City, Japan. A total of 3,165 myringotomies for acute otitis media were performed. The rate of procedures per child-year performed in otitis media in 1-year-old infants decreased significantly in the 2 years after the introduction of public funding for heptavalent pneumococcal conjugate vaccine compared to all years before introduction (potitis media in reducing the financial burden of myringotomy. In addition, this vaccine may help prevent acute otitis media with severe middle ear inflammation in 1-year-old infants.
Clarke, Christopher; Bakaletz, Lauren O; Ruiz-Guiñazú, Javier; Borys, Dorota; Mrkvan, Tomas
Protein D-containing vaccines may decrease acute otitis media (AOM) burden and nasopharyngeal carriage of non-typeable Haemophilus influenzae (NTHi). Protein D-containing pneumococcal conjugate vaccine PHiD-CV (Synflorix, GSK Vaccines) elicits robust immune responses against protein D. However, the phase III Clinical Otitis Media and PneumoniA Study (COMPAS), assessing PHiD-CV efficacy against various pneumococcal diseases, was not powered to demonstrate efficacy against NTHi; only trends of protective efficacy against NTHi AOM in children were shown. Areas covered: This review aims to consider all evidence available to date from pre-clinical and clinical phase III studies together with further evidence emerging from post-marketing studies since PHiD-CV has been introduced into routine clinical practice worldwide, to better describe the clinical utility of protein D in preventing AOM due to NTHi and its impact on NTHi nasopharyngeal carriage. Expert commentary: Protein D is an effective carrier protein in conjugate vaccines and evidence gathered from pre-clinical, clinical and observational studies suggest that it also elicits immune response that can help to reduce the burden of AOM due to NTHi. There remains a need to develop improved vaccines for prevention of NTHi disease, which could be achieved by combining protein D with other antigens.
Ladhani, Shamez N; Andrews, Nick J; Waight, Pauline; Hallis, Bassam; Matheson, Mary; England, Anna; Findlow, Helen; Bai, Xilian; Borrow, Ray; Burbidge, Polly; Pearce, Emma; Goldblatt, David; Miller, Elizabeth
An open, non-randomised study was undertaken in England during 2011-12 to evaluate vaccine antibody responses in infants after completion of the routine primary infant immunisation schedule, which included two doses of meningococcal group C (MenC) conjugate (MCC) vaccine at 3 and 4 months. Any of the three licensed MCC vaccines could be used for either dose, depending on local availability. Healthy term infants registered at participating general practices (GPs) in Hertfordshire and Gloucestershire, UK, were recruited prospectively to provide a single blood sample four weeks after primary immunisation, which was administered by the GP surgery. Vaccination history was obtained at blood sampling. MenC serum bactericidal antibody (SBA) and IgG antibodies against Haemophilus influenzae b (Hib), pertussis toxin (PT), diphtheria toxoid (DT), tetanus toxoid (TT) and thirteen pneumococcal serotypes were analysed according to MCC vaccines received. MenC SBA responses differed significantly (Pvaccine schedule as follows: MenC SBA geometric mean titres (GMTs) were significantly lower in infants receiving a diphtheria cross-reacting material-conjugated MCC (MCC-CRM) vaccine followed by TT-conjugated MCC (MCC-TT) vaccine (82.0; 95% CI, 39-173; n=14) compared to those receiving two MCC-CRM (418; 95% CI, 325-537; n=82), two MCC-TT (277; 95% CI, 223-344; n=79) or MCC-TT followed by MCC-CRM (553; 95% CI, 322-949; n=18). The same group also had the lowest Hib geometric mean concentrations (0.60 μg/mL, 0.27-1.34) compared to 1.85 μg/mL (1.23-2.78), 2.86 μg/mL (2.02-4.05) and 4.26 μg/mL (1.94-9.36), respectively. Our results indicate that MCC vaccines with different carrier proteins are not interchangeable. When several MCC vaccines are available, children requiring more than one dose should receive MCC vaccines with the same carrier protein or, alternatively, receive MCC-TT first wherever possible. Copyright © 2014 Elsevier Ltd. All rights reserved.
Wallace, Lauren; Kapirir, Lydia
To date, research on priority-setting for new vaccines has not adequately explored the influence of the global, national and sub-national levels of decision-making or contextual issues such as political pressure and stakeholder influence and power. Using Kapiriri and Martin's conceptual framework, this paper evaluates priority setting for new vaccines in Uganda at national and sub-national levels, and considers how global priorities can influence country priorities. This study focuses on 2 specific vaccines, the human papilloma virus (HPV) vaccine and the pneumococcal conjugate vaccine (PCV). This was a qualitative study that involved reviewing relevant Ugandan policy documents and media reports, as well as 54 key informant interviews at the global level and national and sub-national levels in Uganda. Kapiriri and Martin's conceptual framework was used to evaluate the prioritization process. Priority setting for PCV and HPV was conducted by the Ministry of Health (MoH), which is considered to be a legitimate institution. While respondents described the priority setting process for PCV process as transparent, participatory, and guided by explicit relevant criteria and evidence, the prioritization of HPV was thought to have been less transparent and less participatory. Respondents reported that neither process was based on an explicit priority setting framework nor did it involve adequate representation from the districts (program implementers) or publicity. The priority setting process for both PCV and HPV was negatively affected by the larger political and economic context, which contributed to weak institutional capacity as well as power imbalances between development assistance partners and the MoH. Priority setting in Uganda would be improved by strengthening institutional capacity and leadership and ensuring a transparent and participatory processes in which key stakeholders such as program implementers (the districts) and beneficiaries (the public) are
Tatiane E. Hirose
Full Text Available Objectives: To evaluate the possible effects of the introduction of the pneumococcal conjugate 10-valent vaccine schedule in the state of Parana on pneumococcal meningitis cases and to assess the distribution of serotypes among cases. Method: Cross-sectional study with retrospective data collection of cases of pneumococcal meningitis in the state of Paraná reported to Sistema de Informação de Agravos de Notificação (SINAN, from 1998 to 2011. A total of 1,339 cases of pneumococcal meningitis were analyzed; 1,205 cases from the pre-vaccine period (1998-2009 were compared to 134 cases from the post-vaccine period (2010-2011. Descriptive and comparative statistical analyses (chi-squared test and prevalence ratio were performed using JMP 5.1.2 statistical software (JMP Statistical Discovery, North Carolina, USA and EPI INFO 6 (Centers for Disease Control and Prevention, Georgia, EUA. Results: There was a significant reduction in the mean rates of incidence and mortality in the general population. The analysis of cases in the pre- and post-vaccination periods in the age groups covered by vaccination (younger than 2 years showed significant reductions in incidence rates (6.01 cases/100,000 to 2.49 cases/100,000 individuals and mortality (1.85 cases/100,000 population to 0.47 cases/100,000 population, while the mean lethality rate did not change significantly. There was a significant reduction in cases whose serotypes are included in the vaccine (80.7% to 53.3%. Conclusion: Even after a short time of use, the 10-valent pneumococcal conjugate vaccine has already had a significant impact in reducing the incidence and mortality of meningitis cases among infants, as well as the reduction of cases whose serotypes are included in the vaccine. Resumo: Objetivos: Avaliar os possíveis efeitos da introdução da vacina pneumocócica conjugada 10 valente no calendário vacinal no Paraná sobre os casos de meningite pneumocócica; avaliar a distribuição dos
Winther, Thilde N; Kristensen, Tim D; Kaltoft, Margit S
Aim: The aim of this study was to document the epidemiology, microbiology and outcome of invasive pneumococcal disease (IPD) among children introduction of the heptavalent pneumococcal conjugate vaccine (PCV7) into the Danish routine...... immunization programme October 2007. Methods: Clinical and microbiological records on cases of IPD in children Hospital, Denmark 1996-2007, were retrospectively reviewed. Results: We identified 106 cases of IPD. The annual incidence of IPD was 11 per 100 000 in children
van den Biggelaar, Anita H J; Pomat, William; Bosco, Anthony; Phuanukoonnon, Suparat; Devitt, Catherine J; Nadal-Sims, Marie A; Siba, Peter M; Richmond, Peter C; Lehmann, Deborah; Holt, Patrick G
Concerns about the risk of inducing immune deviation-associated "neonatal tolerance" as described in mice have restricted the widespread adoption of neonatal vaccination. The aim of this study was to demonstrate the immunological feasibility of neonatal pneumococcal conjugate vaccination (PCV) which could potentially protect high-risk infants in resource poor countries against severe pneumococcal disease and mortality in the early critical period of life. Papua New Guinean infants were randomized to be vaccinated with the 7-valent PCV (7vPCV) at birth, 1 and 2 months (neonatal group, n=104) or at 1, 2 and 3 months of age (infant group, n=105), or to not receive 7vPCV at all (control group, n=109). Analysis of vaccine responses at 3 and 9 months of age demonstrated persistently higher type-1 (IFN-γ) and type-2 (IL-5 and IL-13) T-cell responses to the protein carrier CRM(197) and IgG antibody titres to 7vPCV serotypes in children vaccinated with 7vPCV according to either schedule as compared to unvaccinated children. In a comprehensive immuno-phenotypic analysis at 9 months of age, no differences in the quantity or quality of vaccine-specific T cell memory responses were found between neonatal vaccinations versus children given their first PCV dose at one month. Hospitalization rates in the first month of life did not differ between children vaccinated with PCV at birth or not. These findings demonstrate that neonatal 7vPCV vaccination is safe and not associated with immunological tolerance. Neonatal immunisation schedules should therefore be considered in high-risk areas where this may result in improved vaccine coverage and the earliest possible protection against pneumococcal disease and death. Copyright © 2011 Elsevier Ltd. All rights reserved.
Bosch, Astrid A T M; van Houten, Marlies A.; Bruin, Jacob P.; Wijmenga-Monsuur, Alienke J.; Trzciński, Krzysztof; Bogaert, Debby; Rots, Nynke Y.; Sanders, Elisabeth A M
After introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in the infant national immunization program (NIP) in the Netherlands in 2006, Streptococcus pneumoniae strains of the non-vaccine serotype 19A emerged and became the dominant serotype in carriage in children and their parents.
Dotres, Carlos P; Puga, Rinaldo; Ricardo, Yariset; Broño, Carmen R; Paredes, Beatriz; Echemendía, Vladimir; Rosell, Sandra; González, Nadezhda; García-Rivera, Dagmar; Valdés, Yury; Goldblatt, David; Vérez-Bencomo, Vicente
A new heptavalent conjugate vaccine (PCV7-TT) is under development in Cuba. PCV7-TT contains 2 μg of serotypes 1, 5, 14, 18C, 19F, 23F and 4 μg of 6B, each one conjugated to tetanus toxoid (TT). This vaccine was designed with the serotypes that cause most invasive pneumococcal diseases (IPD) worldwide. In the present study, we investigated the safety and explored the immunogenicity of PCV7-TT during a controlled, randomized and double blind clinical trial phase I in 4-5-year-old children. PCV7-TT was well tolerated and as safe as Synflorix used as control vaccine. Following a single-dose vaccination, all individual serotypes included in PCV7-TT induced statistically significant increase of IgG GMC and OPA GMT. These are the first clinical results of PCV7-TT in children and they pave the way toward next clinical trials in children and infants. This clinical trial was published in the Cuban Public Register of Clinical Trials with code RPCEC00000173. Copyright © 2014 Elsevier Ltd. All rights reserved.
Perry, Caroline M
The meningococcal groups C and Y and Haemophilus b (Hib) tetanus toxoid conjugate vaccine (HibMenCY-TT) contains Neisseria meningitidis serogroup C and Y capsular polysaccharide antigens, and Hib capsular polysaccharide [polyribosyl-ribitol-phosphate (PRP)]. The HibMenCY-TT vaccine is available in the USA for use as active immunization to prevent invasive disease caused by N. meningitidis serogroups C (MenC) and Y (MenY), and Hib in children 6 weeks-18 months of age. HibMenCY-TT is the first meningococcal vaccine available for use in the USA that can be administered to infants as young as 6 weeks of age. In a randomized, controlled, phase III clinical trial, the HibMenCY-TT vaccine, administered to infants at 2, 4, 6 and 12-15 months of age, was immunogenic against MenC and MenY, and met the prespecified criteria for immunogenicity. Anti-PRP antibodies, which have been shown to correlate with protection against Hib invasive disease, were also induced in the infants who received the HibMenCY-TT vaccine, with induced levels of this antibody noninferior to those occurring in the control group of infants who received a Hib tetanus toxoid conjugate vaccine at 2, 4, and 6 months and a single dose of Hib conjugated to N. meningitidis outer membrane protein at 12-15 months. In several randomized, controlled clinical trials, HibMenCY-TT was coadministered with vaccines that are routinely administered to infants and toddlers in the USA. These vaccines included: diphtheria and tetanus toxoids and acellular pertussis adsorbed, hepatitis B (recombinant) and inactivated poliovirus vaccine combined; 7-valent Streptococcus pneumoniae polysaccharide conjugate vaccine; measles, mumps and rubella vaccine; and varicella vaccine. Coadministration of these vaccines did not interfere with the immunogenicity of the HibMenCY-TT vaccine. Similarly, immune responses to the coadministered vaccines were not affected by the HibMenCY-TT vaccine. The tolerability profile of the Hib
Warren, Joshua L.; Shioda, Kayoko; Kürüm, Esra
Background Pneumococcal conjugate vaccines (PCVs) are being used worldwide. A key question is whether the impact of PCVs on pneumonia is similar in low- and high-income populations. However, most low-income countries, where the burden of disease is greatest, lack reliable data that can be used...... to evaluate the impact. Data from middle-income countries that have both low- and high-income subpopulations can provide a proxy measure for the impact of the vaccine in low-income countries. Methods We evaluated the impact of PCV10 on hospitalizations for all-cause pneumonia in Brazil, a middle......-income country with localities that span a broad range of human development index (HDI) levels. We used complementary time series and spatiotemporal methods (synthetic controls and hierarchical Bayesian spatial regression) to test whether the decline in pneumonia hospitalizations associated with vaccine...
Grant A Mackenzie
Full Text Available Routine use of pneumococcal conjugate vaccines (PCVs in developing countries is expected to lead to a significant reduction in childhood deaths. However, PCVs have been associated with replacement disease with non-vaccine serotypes. We established a population-based surveillance system to document the direct and indirect impact of PCVs on the incidence of invasive pneumococcal disease (IPD and radiological pneumonia in those aged 2 months and older in The Gambia, and to monitor changes in serotype-specific IPD. Here we describe how this surveillance system was set up and is being operated as a partnership between the Medical Research Council Unit and the Gambian Government. This surveillance system is expected to provide crucial information for immunisation policy and serves as a potential model for those introducing routine PCV vaccination in diverse settings.
Blagden, Sarah; Hungerford, Daniel; Limmer, Mark
In 2015 the meningococcal ACWY (MenACWY) vaccination was introduced amongst adolescents in England following increased incidence and mortality associated with meningococcal group W. MenACWY vaccination uptake data for 17-18 years old and students delivered in primary care were obtained for 20 National Health Service clinical commissioning groups (CCGs) via the ImmForm vaccination system. Data on general practice characteristics, encompassing demographics and patient satisfaction variables, were extracted from the National General Practice Profiles resource. Univariable analysis of the associations between practice characteristics and vaccination was performed, followed by multivariable negative binomial regression. Data were utilized from 587 general practices, accounting for ~8% of all general practices in England. MenACWY vaccination uptake varied from 20.8% to 46.8% across the CCGs evaluated. Upon multivariable regression, vaccination uptake increased with increasing percentage of patients from ethnic minorities, increasing percentage of patients aged 15-24 years, increasing percentage of patients that would recommend their practice and total Quality and Outcomes Framework achievement for the practice. Conversely, vaccination uptake decreased with increasing deprivation. This study has identified several factors independently associated with MenACWY vaccination in primary care. These findings will enable a targeted approach to improve general practice-level vaccination uptake. © The Author(s) 2018. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: email@example.com
Wortley Pascale M
Full Text Available Abstract Background In February 2005, the US Advisory Committee on Immunization Practices recommended the new meningococcal conjugate vaccine (MCV4 for routine use among 11- to 12-year-olds (at the preadolescent health-care visit, 14- to 15-year-olds (before high-school entry, and groups at increased risk. Vaccine distribution started in March; however, in July, the manufacturer reported inability to meet demand and widespread MCV4 shortages were reported. Our objectives were to determine early uptake patterns among target (11-12 and 14-15 year olds and non-target (13- plus 16-year-olds age groups. A post hoc analysis was conducted to compare seasonal uptake patterns of MCV4 with polysaccharide meningococcal (MPSV4 and tetanus diphtheria (Td vaccines. Methods We analyzed data for adolescents 11-16 years from five managed care organizations participating in the Vaccine Safety Datalink (VSD. For MCV4, we estimated monthly and cumulative coverage during 2005 and calculated risk ratios. For MPSV4 and Td, we combined 2003 and 2004 data and compared their seasonal uptake patterns with MCV4. Results Coverage for MCV4 during 2005 among the 623,889 11-16 years olds was 10%. Coverage for 11-12 and 14-15 year olds was 12% and 11%, respectively, compared with 8% for 13- plus 16-year-olds (p Conclusion A surge in vaccine uptake between June and August was observed among adolescents for MCV4, MPSV4 and Td vaccines. The increase in summer-time vaccinations and vaccination of non-targeted adolescents coupled with supply limitations likely contributed to the reported shortages of MCV4 in 2005.
Jolin, Jonathan; van Aalst, Robertus; Volpp, Bryan; Taylor, Thomas; Cohen, Emily
Pneumococcal infections are an important source of morbidity and mortality in older adults and persons with compromised immune systems. New recommendations from the Advisory Committee on Immunization Practices (ACIP) became available September 2014, which included recommendations for the use of the 13-valent pneumococcal conjugate vaccine (PCV13). A study was conducted to increase the PCV13 vaccination rates of hospitalized patients at the White River Junction Veterans Affairs Medical Center (White River Junction, Vermont) through the use of a resident-driven quality improvement (QI) project. From December 2014 through April 2016, 16 internal medicine inpatient residents addressed inpatient PCV13 vaccination rates by participating in the facility's QI curriculum. Eight Plan-Do-Study-Act cycles were used, including discharge template editing, electronic reminders, and the discovery of a vaccination administration documentation error in the record through data validation. The measure was the monthly percentage of patients who received PCV13 vaccination (vaccination completion rate) of those discharged from the hospital medicine service who were due for PCV13 vaccination. The percentage of veterans discharged with an up-to-date PCV13 vaccination on discharge increased from approximately 30% to 87% and was sustained. Despite being driven by many different residents, this project demonstrates that continuous improvement can be achieved through a structured and iterative process while providing active learning of core QI concepts to residents. It also displays a method in which new guidelines can be incorporated into practice in an effective manner. Finally, this project is an example of how resident-driven data validation can lead to further improvement. Published by Elsevier Inc.
Hamidi, Ahd; Kreeftenberg, Hans; V D Pol, Leo; Ghimire, Saroj; V D Wielen, Luuk A M; Ottens, Marcel
Vaccination is one of the most successful public health interventions being a cost-effective tool in preventing deaths among young children. The earliest vaccines were developed following empirical methods, creating vaccines by trial and error. New process development tools, for example mathematical modeling, as well as new regulatory initiatives requiring better understanding of both the product and the process are being applied to well-characterized biopharmaceuticals (for example recombinant proteins). The vaccine industry is still running behind in comparison to these industries. A production process for a new Haemophilus influenzae type b (Hib) conjugate vaccine, including related quality control (QC) tests, was developed and transferred to a number of emerging vaccine manufacturers. This contributed to a sustainable global supply of affordable Hib conjugate vaccines, as illustrated by the market launch of the first Hib vaccine based on this technology in 2007 and concomitant price reduction of Hib vaccines. This paper describes the development approach followed for this Hib conjugate vaccine as well as the mathematical modeling tool applied recently in order to indicate options for further improvements of the initial Hib process. The strategy followed during the process development of this Hib conjugate vaccine was a targeted and integrated approach based on prior knowledge and experience with similar products using multi-disciplinary expertise. Mathematical modeling was used to develop a predictive model for the initial Hib process (the 'baseline' model) as well as an 'optimized' model, by proposing a number of process changes which could lead to further reduction in price. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:568-580, 2016. © 2016 American Institute of Chemical Engineers.
Full Text Available Definition of the optimal pneumococcal vaccine strategy in HIV-infected adults is still under evaluation. We aimed to compare immunogenicity and safety of the 13-valent pneumococcal conjugate vaccine (PCV13 versus the 23-valent polysaccharide vaccine (PPSV23 in HIV-infected adults.We performed a pilot, prospective controlled study enrolling HIV-infected pneumococcal vaccine-naïve outpatients, aged 18-65 years with CD4 counts ≥200 cells/μL. Eligible subjects were recruited into two parallel groups: group 1 (n = 50 received two doses of PCV13 eight weeks apart, and group 2 (n = 50 received one dose of PPSV23, as part of their standard of care. Anti-pneumococcal capsular polysaccharide immunoglobulin G concentrations were quantified by ELISA at baseline, 8, 24 and 48 weeks. Clinical and viro-immunological follow-up was performed at the same time points. Unvaccinated, age-matched HIV-negative adults (n = 100 were also enrolled as baseline controls.Pre-vaccination specific IgG titers for each pneumococcal antigen did not differ between study groups but they were constantly lower than those from the HIV-negative controls. After immunization, significant increases in IgG titers were observed in both study groups at each time point compared to baseline, but response to serotype 3 was blunted in group 1. Antibody titers for each antigen did not differ between study groups at week 48. Overall, the proportion of subjects achieving seroprotection and seroconversion to all serotypes was comparable between groups. A marked decrease in IgG levels over time was observed with both vaccines. No relevant adverse reactions were reported in either group.In this population with favorable immune profile, no relevant differences were observed in immunogenicity between PCV13 and PPSV23. Both vaccines were safe and well tolerated.ClinicalTrials.gov NCT02123433.
Saez-Llorens, Xavier; Aguilera Vaca, Diana Catalina; Abarca, Katia; Maho, Emmanuelle; Graña, Maria Gabriela; Heijnen, Esther; Smolenov, Igor; Dull, Peter M
This phase 2 study assessed the immunogenicity, safety, and reactogenicity of investigational formulations of meningococcal ABCWY vaccines, consisting of recombinant proteins (rMenB) and outer membrane vesicle (OMV) components of a licensed serogroup B vaccine, combined with components of a licensed quadrivalent meningococcal glycoconjugate vaccine (MenACWY-CRM). A total of 495 healthy adolescents were randomized to 6 groups to receive 2 doses (Months 0, 2) of one of 4 formulations of rMenB antigens, with or without OMV, combined with MenACWY-CRM, or 2 doses of rMenB alone or one dose of MenACWY-CRM then a placebo. Immunogenicity was assessed by serum bactericidal assay with human complement (hSBA) against serogroups ACWY and serogroup B test strains; solicited reactions and any adverse events (AEs) were assessed. Two MenABCWY vaccinations elicited robust ACWY immune responses, with higher seroresponse rates than one dose of MenACWY-CRM. Bactericidal antibody responses against the rMenB antigens and OMV components were highest in subjects who received 2 doses of OMV-containing MenABCWY formulations, with ≥68% of subjects achieving hSBA titers ≥5 against each of the serogroup B test strains. After the first dose, solicited local reaction rates were higher in the MenABCWY or rMenB groups than the MenACWY-CRM group, but similar across groups after the second dose, consisting mainly of transient injection site pain. Fever (≥38.0°C) was rare and there were no vaccine-related serious AEs. In conclusion, investigational MenABCWY formulations containing OMV components elicited highly immunogenic responses against meningococcal serogroups ACWY, as well as serogroup B test strains, with an acceptable safety profile. [NCT01210885].
Li, Rong-cheng; Li, Feng-xiang; Li, Yan-ping
To evaluate the safety and immunogenicity of the booster dose of 7 valent pneumococcal conjugate vaccine (PCV7) to the healthy Chinese toddlers who had received 3 primary doses. Four hundred and eighty-eight Chinese toddlers received a booster dose of PCV7 at age of 12-15 months following a primary series of the vaccine given at ages 3, 4, 5 months separately with Diphtheria Tetanus Acellular Pertussis Combined Vaccine (DTaP) in Group 1 or concurrently with DTaP in Group 2. Following the booster dose immunization, each subject was followed up for 30 days to observe the safety of the vaccine. Blood samples were taken from a subset of subjects prior and post 30 days the booster dose immunization to evaluate immunogenicity. A high proportion of subjects in Group 1 (89%) and Group 2 (91%) remained afebrile after the booster dose. Local reactions to the PCV7 booster dose were generally mild. For each serotype, the rise in GMC (post-/pre-vaccination) showed a statistically significant difference (P<0.0001) between both groups. PCV7 administered as a booster dose is generally safe, well tolerate, and immunogenic in healthy Chinese toddlers.
Full Text Available BACKGROUND: We investigated the effect of the 7-valent pneumococcal conjugate vaccine (PCV7 programme in England on serotype-specific carriage and invasive disease to help understand its role in serotype replacement and predict the impact of higher valency vaccines. METHODS AND FINDINGS: Nasopharyngeal swabs were taken from children <5 y old and family members (n=400 2 y after introduction of PCV7 into routine immunization programs. Proportions carrying Streptococcus pneumoniae and serotype distribution among carried isolates were compared with a similar population prior to PCV7 introduction. Serotype-specific case carrier ratios (CCRs were estimated using national data on invasive disease. In vaccinated children and their contacts vaccine-type (VT carriage decreased, but was offset by an increase in non-VT carriage, with no significant overall change in carriage prevalence, odds ratio 1.06 (95% confidence interval 0.76-1.49. The lower CCRs of the replacing serotypes resulted in a net reduction in invasive disease in children. The additional serotypes covered by higher valency vaccines had low carriage but high disease prevalence. Serotype 11C emerged as predominant in carriage but caused no invasive disease whereas 8, 12F, and 22F emerged in disease but had very low carriage prevalence. CONCLUSION: Because the additional serotypes included in PCV10/13 have high CCRs but low carriage prevalence, vaccinating against them is likely to significantly reduce invasive disease with less risk of serotype replacement. However, a few serotypes with high CCRs could mitigate the benefits of higher valency vaccines. Assessment of the effect of PCV on carriage as well as invasive disease should be part of enhanced surveillance activities for PCVs. Please see later in the article for the Editors' Summary.
Kulkarni, Prasad S.; Socquet, Muriel; Jadhav, Suresh S.; Kapre, Subhash V.; LaForce, F. Marc; Poonawalla, Cyrus S.
Background. In 2002, the Meningitis Vaccine Project (MVP) chose the Serum Institute of India, Ltd (SIIL), as its manufacturing partner to establish a product development partnership (PDP) with the Meningitis Vaccine Project (MVP). MVP was a collaboration between PATH and the World Health Organization (WHO) to develop meningococcal conjugate vaccines for sub-Saharan Africa. Method. From the outset, SIIL recognized that a partnership with MVP carried some risk but also offered important opportunities for accessing new conjugate vaccine technology and know-how. Over 3 years, SIIL successfully accepted technology transfer for the group A meningococcal polysaccharide from SynCo Bio Partners and a conjugation method from the US Food and Drug Administration. Results. SIIL successfully scaled up production of a group A meningococcal conjugate vaccine that used SIIL tetanus toxoid as the carrier protein. Phase 1 studies began in India in 2005, followed by phase 2/3 studies in Africa and India. A regulatory dossier was submitted to the Indian authorities in April 2009 and WHO in September 2009. Export license was granted in December 2009, and WHO prequalification was obtained in June 2010. Vaccine was introduced at public scale in Burkina Faso that December. The group A meningococcal conjugate vaccine was named MenAfriVac, and is the first internationally qualified vaccine developed outside of big pharma. Conclusions. The project proved to be a sound investment for SIIL and is a concrete example of the potential for PDPs to provide needed products for resource-poor countries. PMID:26553678
Perrett, K P; John, T M; Jin, C; Kibwana, E; Yu, L-M; Curtis, N; Pollard, A J
Protection against Haemophilus influenzae type b (Hib), a rapidly invading encapsulated bacteria, is dependent on maintenance of an adequate level of serum antibody through early childhood. In many countries, Hib vaccine booster doses have been implemented after infant immunization to sustain immunity. We investigated the long-term persistence of antibody and immunological memory in primary-school children following infant (with or without booster) Hib vaccination. Anti-polyribosylribitol phosphate (PRP) immunoglobulin G (IgG) concentration and the frequency of circulating Hib-specific memory B cells were measured before a booster of a Hib-serogroup C meningococcal (MenC) conjugate vaccine and again 1 week, 1 month, and 1 year after the booster in 250 healthy children aged 6-12 years in an open-label phase 4 clinical study. Six to 12 years following infant priming with 3 doses of Hib conjugate vaccine, anti-PRP IgG geometric mean concentrations were 3.11 µg/mL and 0.71 µg/mL and proportions with anti-PRP IgG ≥1.0 µg/mL were 79% and 43% in children who had or had not, respectively, received a fourth Hib conjugate vaccine dose (mean age, 3.9 years). Higher baseline and post-Hib-MenC booster responses (anti-PRP IgG and memory B cells) were found in younger children and in those who had received a fourth Hib dose. Sustained Hib conjugate vaccine-induced immunity in children is dependent on time since infant priming and receipt of a booster. Understanding the relationship between humoral and cellular immunity following immunization with conjugate vaccines may direct vaccine design and boosting strategies to sustain individual and population immunity against encapsulated bacteria in early childhood. Clinical Trials Registration ISRCTN728588998.
Otto, Robert B D; Burkin, Karena; Amir, Saba Erum; Crane, Dennis T; Bolgiano, Barbara
The basis of Haemophilus influenzae type b (Hib) and Neisseria meningitidis serogroup C (MenC) glycoconjugates binding to aluminum-containing adjuvants was studied. By measuring the amount of polysaccharide and protein in the non-adsorbed supernatant, the adjuvant, aluminum phosphate, AlPO4, was found to be less efficient than aluminum hydroxide, Al(OH)3 at binding to the conjugates, at concentrations relevant to licensed vaccine formulations and when equimolar. At neutral pH, binding of TT conjugates to AlPO4 was facilitated through the carrier protein, with only weak binding of AlPO4 to CRM197 being observed. There was slightly higher binding of either adjuvant to tetanus toxoid conjugates, than to CRM197 conjugates. This was verified in AlPO4 formulations containing DTwP-Hib, where the adsorption of TT-conjugated Hib was higher than CRM197-conjugated Hib. At neutral pH, the anionic Hib and MenC polysaccharides did not appreciably bind to AlPO4, but did bind to Al(OH)3, due to electrostatic interactions. Phosphate ions reduced the binding of the conjugates to the adjuvants. These patterns of adjuvant adsorption can form the basis for future formulation studies with individual and combination vaccines containing saccharide-protein conjugates. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.
Otto, Robert B.D.; Burkin, Karena; Amir, Saba Erum; Crane, Dennis T.; Bolgiano, Barbara
The basis of Haemophilus influenzae type b (Hib) and Neisseria meningitidis serogroup C (MenC) glycoconjugates binding to aluminum-containing adjuvants was studied. By measuring the amount of polysaccharide and protein in the non-adsorbed supernatant, the adjuvant, aluminum phosphate, AlPO4, was found to be less efficient than aluminum hydroxide, Al(OH)3 at binding to the conjugates, at concentrations relevant to licensed vaccine formulations and when equimolar. At neutral pH, binding of TT conjugates to AlPO4 was facilitated through the carrier protein, with only weak binding of AlPO4 to CRM197 being observed. There was slightly higher binding of either adjuvant to tetanus toxoid conjugates, than to CRM197 conjugates. This was verified in AlPO4 formulations containing DTwP–Hib, where the adsorption of TT-conjugated Hib was higher than CRM197-conjugated Hib. At neutral pH, the anionic Hib and MenC polysaccharides did not appreciably bind to AlPO4, but did bind to Al(OH)3, due to electrostatic interactions. Phosphate ions reduced the binding of the conjugates to the adjuvants. These patterns of adjuvant adsorption can form the basis for future formulation studies with individual and combination vaccines containing saccharide-protein conjugates. PMID:26194164
Thomas E Delea
Full Text Available Public health programs to prevent invasive meningococcal disease (IMD with monovalent serogroup C meningococcal conjugate vaccine (MCV-C and quadrivalent meningococcal conjugate vaccines (MCV-4 in infancy and adolescence vary across Canadian provinces. This study evaluated the cost-effectiveness of various vaccination strategies against IMD using current and anticipated future pricing and recent epidemiology.A cohort model was developed to estimate the clinical burden and costs (CAN$2014 of IMD in the Canadian population over a 100-year time horizon for three strategies: (1 MCV-C in infants and adolescents (MCV-C/C; (2 MCV-C in infants and MCV-4 in adolescents (MCV-C/4; and (3 MCV-4 in infants (2 doses and adolescents (MCV-4/4. The source for IMD incidence was Canadian surveillance data. The effectiveness of MCV-C was based on published literature. The effectiveness of MCV-4 against all vaccination regimens was assumed to be the same as for MCV-C regimens against serogroup C. Herd effects were estimated by calibration to estimates reported in prior analyses. Costs were from published sources. Vaccines prices were projected to decline over time reflecting historical procurement trends.Over the modeling horizon there are a projected 11,438 IMD cases and 1,195 IMD deaths with MCV-C/C; expected total costs are $597.5 million. MCV-C/4 is projected to reduce cases of IMD by 1,826 (16% and IMD deaths by 161 (13%. Vaccination costs are increased by $32 million but direct and indirect IMD costs are projected to be reduced by $46 million. MCV-C/4 is therefore dominant vs. MCV-C/C in the base case. Cost-effectiveness of MCV-4/4 was $111,286 per QALY gained versus MCV-C/4 (2575/206 IMD cases/deaths prevented; incremental costs $68 million.If historical trends in Canadian vaccines prices continue, use of MCV-4 instead of MCV-C in adolescents may be cost-effective. From an economic perspective, switching to MCV-4 as the adolescent booster should be considered.
Delea, Thomas E; Weycker, Derek; Atwood, Mark; Neame, Dion; Alvarez, Fabián P; Forget, Evelyn; Langley, Joanne M; Chit, Ayman
Public health programs to prevent invasive meningococcal disease (IMD) with monovalent serogroup C meningococcal conjugate vaccine (MCV-C) and quadrivalent meningococcal conjugate vaccines (MCV-4) in infancy and adolescence vary across Canadian provinces. This study evaluated the cost-effectiveness of various vaccination strategies against IMD using current and anticipated future pricing and recent epidemiology. A cohort model was developed to estimate the clinical burden and costs (CAN$2014) of IMD in the Canadian population over a 100-year time horizon for three strategies: (1) MCV-C in infants and adolescents (MCV-C/C); (2) MCV-C in infants and MCV-4 in adolescents (MCV-C/4); and (3) MCV-4 in infants (2 doses) and adolescents (MCV-4/4). The source for IMD incidence was Canadian surveillance data. The effectiveness of MCV-C was based on published literature. The effectiveness of MCV-4 against all vaccination regimens was assumed to be the same as for MCV-C regimens against serogroup C. Herd effects were estimated by calibration to estimates reported in prior analyses. Costs were from published sources. Vaccines prices were projected to decline over time reflecting historical procurement trends. Over the modeling horizon there are a projected 11,438 IMD cases and 1,195 IMD deaths with MCV-C/C; expected total costs are $597.5 million. MCV-C/4 is projected to reduce cases of IMD by 1,826 (16%) and IMD deaths by 161 (13%). Vaccination costs are increased by $32 million but direct and indirect IMD costs are projected to be reduced by $46 million. MCV-C/4 is therefore dominant vs. MCV-C/C in the base case. Cost-effectiveness of MCV-4/4 was $111,286 per QALY gained versus MCV-C/4 (2575/206 IMD cases/deaths prevented; incremental costs $68 million). If historical trends in Canadian vaccines prices continue, use of MCV-4 instead of MCV-C in adolescents may be cost-effective. From an economic perspective, switching to MCV-4 as the adolescent booster should be considered.
Indianara Maria Grando
Full Text Available The objective of this study was to analyze the impact of vaccination against Streptococcus pneumoniae on the morbidity and mortality from pneumococcal meningitis in children ≤ 2 years in Brazil, from 2007 to 2012. This is a descriptive study and ecological analysis using data from the Information System on Notifiable Diseases. Pre-vaccination (2007-2009 and post-vaccination (2011-2012 periods were defined to compare incidence rates and mortality. A total of 1,311 cases and 430 deaths were reported during the study period. Incidence decreased from 3.70/100,000 in 2007 to 1.84/100,000 in 2012, and mortality decreased from 1.30/100,000 to 0.40/100,000, or 50% and 69% respectively, with the greatest impact in the 6-11 month age group. This decrease in Pneumococcal meningitis morbidity and mortality rates two years after introduction of the 10-valent pneumococcal conjugate vaccine suggests its effectiveness.
Licciardi, Paul V; Toh, Zheng Quan; Clutterbuck, Elizabeth A; Balloch, Anne; Marimla, Rachel A; Tikkanen, Leena; Lamb, Karen E; Bright, Kathryn J; Rabuatoka, Uraia; Tikoduadua, Lisi; Boelsen, Laura K; Dunne, Eileen M; Satzke, Catherine; Cheung, Yin Bun; Pollard, Andrew J; Russell, Fiona M; Mulholland, Edward K
A randomized controlled trial in Fiji examined the immunogenicity and effect on nasopharyngeal carriage after 0, 1, 2, or 3 doses of 7-valent pneumococcal conjugate vaccine (PCV7; Prevnar) in infancy followed by 23-valent pneumococcal polysaccharide vaccine (23vPPV; Pneumovax) at 12 months of age. At 18 months of age, children given 23vPPV exhibited immune hyporesponsiveness to a micro-23vPPV (20%) challenge dose in terms of serotype-specific IgG and opsonophagocytosis, while 23vPPV had no effect on vaccine-type carriage. This follow-up study examined the long-term effect of the 12-month 23vPPV dose by evaluating the immune response to 13-valent pneumococcal conjugate vaccine (PCV13) administration 4 to 5 years later. Blood samples from 194 children (now 5-7 years old) were taken before and 28 days after PCV13 booster immunization. Nasopharyngeal swabs were taken before PCV13 immunization. We measured levels of serotype-specific IgG to all 13 vaccine serotypes, opsonophagocytosis for 8 vaccine serotypes, and memory B-cell responses for 18 serotypes before and after PCV13 immunization. Paired samples were obtained from 185 children. There were no significant differences in the serotype-specific IgG, opsonophagocytosis, or memory B-cell response at either time point between children who did or did not receive 23vPPV at 12 months of age. Nasopharyngeal carriage of PCV7 and 23vPPV serotypes was similar among the groups. Priming with 1, 2, or 3 PCV7 doses during infancy did not affect serotype-specific immunity or carriage. Immune hyporesponsiveness induced by 23vPPV in toddlers does not appear to be sustained among preschool children in this context and does not affect the pneumococcal carriage rate in this age group. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
Full Text Available In some countries, the invasive disease caused by Haemophilus influenzae type b (Hib has been practically eliminated thanks to vaccination. However, in much of the developing world, meningitides and pneumonias caused by these bacteria continue to be a major cause of childhood morbidity and mortality, as well as high hospitalization costs. Because safe and effective conjugate vaccines are now available, the Special Program for Vaccines and Immunization of the Pan American Health Organization has recommended introducing them into the regular vaccination regimen of as many countries as possible. This has been done in Chile and Uruguay, where the Hib vaccine now forms part of the regular vaccination routine. When the vaccine was being introduced, both countries had difficulties they could have avoided if they had known of the experiences of other nations. Therefore, these two countries now offer the lessons they learned to other nations considering introducing the vaccine into their immunization programs. The most important lessons were to: strengthen the epidemiological surveillance system sufficiently in advance of introducing the vaccine; with th support of sicentific societies, present the technical information that justifies introducing the vaccine; seek community backing and acceptance; precisely establish in advance the presentation and dosage of the vaccine that is most appropriate for the country; and be certain to have the political and legal decisions needed to ensure the continuity of Hib vaccination in the future.
Barington, T; Heilmann, C; Andersen, V
The human B-lymphocyte response to protein-conjugated polysaccharide antigens has not previously been studied at the cellular level. In order to do so, we developed and evaluated haemolytic plaque-forming cell assays detecting Haemophilus influenzae type b (Hib) capsular polysaccharide-specific a......The human B-lymphocyte response to protein-conjugated polysaccharide antigens has not previously been studied at the cellular level. In order to do so, we developed and evaluated haemolytic plaque-forming cell assays detecting Haemophilus influenzae type b (Hib) capsular polysaccharide...
Zhang, Guiqiang; Cheng, Gong; Jia, Peiyuan; Jiao, Siming; Feng, Cui; Hu, Tao; Liu, Hongtao; Du, Yuguang
Chitosan oligosaccharides (COS), the degraded products of chitosan, have been demonstrated to have versatile biological functions. In primary studies, it has displayed significant adjuvant effects when mixed with other vaccines. In this study, chitosan oligosaccharides with different deacetylation degrees were prepared and conjugated to porcine circovirus type 2 (PCV2) subunit vaccine to enhance its immunogenicity. The vaccine conjugates were designed by the covalent linkage of COSs to PCV2 molecules and administered to BALB/c mice three times at two-week intervals. The results indicate that, as compared to the PCV2 group, COS-PCV2 conjugates remarkably enhanced both humoral and cellular immunity against PCV2 by promoting lymphocyte proliferation and initiating a mixed T-helper 1 (Th1)/T-helper 2 (Th2) response, including raised levels of PCV2-specific antibodies and an increased production of inflammatory cytokines. Noticeably, with the increasing deacetylation degree, the stronger immune responses to PCV2 were observed in the groups with COS-PCV2 vaccination. In comparison with NACOS (chitin oligosaccharides)-PCV2 and LCOS (chitosan oligosaccharides with low deacetylation degree)-PCV2, HCOS (chitosan oligosaccharides with high deacetylation degree)-PCV2 showed the highest adjuvant effect, even comparable to that of PCV2/ISA206 (a commercialized adjuvant) group. In summary, COS conjugation might be a viable strategy to enhance the immune response to PCV2 subunit vaccine, and the adjuvant effect was positively correlated with the deacetylation degree of COS.
Immunogenicity and safety of a booster dose of the 13-valent pneumococcal conjugate vaccine in children primed with the 10-valent or 13-valent pneumococcal conjugate vaccine in the Czech Republic and Slovakia.
Urbancikova, Ingrid; Prymula, Roman; Goldblatt, David; Roalfe, Lucy; Prymulova, Karolina; Kosina, Pavel
Although both the 13-valent pneumococcal conjugate vaccine (PCV13) and the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) are widely used, it is unclear how interchangeable they are in terms of immunogenicity. Two phase 3, open-label, multicenter studies were conducted to assess the immunogenicity and safety of a booster dose of PCV13 in children primed with PHiD-CV or PCV13. In the Czech Republic, 12-15-month-old children received a PCV13 booster after 3-dose priming with either PHiD-CV or PCV13. In Slovakia, 11-12-month-old children received PCV13 following 2-dose priming with either PHiD-CV or PCV13. Serum IgG concentrations were assessed by enzyme-linked immunosorbent assay and functional antibodies were assessed by opsonophagocytic assay (OPA) before the booster and at 1 and 12months afterward. The primary objective of these studies was to assess non-inferiority of OPA titers for serotype 19A in PHiD-CV-primed subjects compared to those in PCV13-primed children 1month post-booster. A total of 98 subjects in the Czech Republic and 89 subjects in Slovakia were included. One month after the PCV13 booster dose, the IgG and OPA immune responses to serotype 19A in subjects primed with 2 or 3 doses of PHiD-CV were non-inferior to those in subjects primed with PCV13. Non-inferior and persistent immune responses to most other vaccine serotypes were also observed after the PCV13 booster in PHiD-CV-primed subjects. No safety issues were raised in either study. Overall, robust IgG and OPA immunological responses were observed after booster vaccination with PCV13 in children primed with 2 or 3 doses of PHiD-CV or PCV13, including for serotypes not included in PHiD-CV. These results suggest that these vaccines are interchangeable in terms of safety and immunogenicity and that PCV13 can be used as a booster in the context of mixed schedules. (EudraCT numbers: 2012-005366-35 and 2012-005367-27). Copyright © 2017 Elsevier Ltd
General health, otitis media, nasopharyngeal carriage and middle ear microbiology in Northern Territory Aboriginal children vaccinated during consecutive periods of 10-valent or 13-valent pneumococcal conjugate vaccines.
Leach, Amanda J; Wigger, Christine; Beissbarth, Jemima; Woltring, Donna; Andrews, Ross; Chatfield, Mark D; Smith-Vaughan, Heidi; Morris, Peter S
This study aims to monitor the prevalence of suppurative otitis media in remote Indigenous communities after introduction of 13-valent pneumococcal conjugate vaccine (PCV13) in October 2011. We previously reported a decline in suppurative OM following replacement of PCV7 by 10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV10) in October 2009. We continued regular surveillance in remote Indigenous communities between February 2010 and August 2013. This analysis reports the general health, otitis media (OM), nasopharyngeal (NP) carriage and middle ear microbiology in children less than 36 months of age who received a primary course of at least two doses of PHiD-CV10 or PCV13, and not more than one dose of another pneumococcal vaccine. Mean ages of 511 PHiD-CV10- and 140 PCV13-vaccinated children were 19 and 13 months, respectively. Most children received 3-dose non-mixed PCV schedules. At the time of assessment, general health was poor and prevalence of risk factors was high in both groups: overall, around 14% of children had scabies, 20% had impetigo, 59% had runny nose and 39% had cough. Average household size was 8 persons, and 60% of the mothers smoked. Bilaterally normal middle ears were detected in 10% and 7%, respectively. OM with effusion (OME), almost all bilateral, was diagnosed in 52% and 50%, any suppurative OM (acute OM or any tympanic membrane perforation [TMP]) in 37% and 41%, and TMP in 14% and 12%, respectively. Children in the PCV13 group had significantly less NP carriage of combined Streptococcus pneumoniae (Spn) and non-typeable Haemophilus influenzae (NTHi) (62% versus 51%) but significantly more polymicrobial (Spn and NTHi) middle ear cultures (12% versus 43%), and significantly less Staphylococcus aureus-positive middle ears (40% versus 7%). Although NP carriage of pneumococcal serotype 19A was low in the PCV13 group, serotypes 19F and 23F persist. The general health, particularly ear health, of little children
Full Text Available Smoldering multiple myeloma (SMM is an asymptomatic clonal plasma cell disorder that frequently progress to multiple myeloma (MM, a disease at high risk of pneumococcal infections. Moreover, if the polysaccharide vaccine is poorly immunogenic in MM, the 13-valent conjugated vaccine has never been tested in clonal plasma cell disorders. We evaluated its immunogenicity for 7 serotypes in 20 patients ≥ 50 years of age with smoldering multiple myeloma (SMM pre and post routine-vaccination with PCV13.Concentrations of IgG specific for 7 serotypes were measured at baseline, 1, 6, and 12 months after vaccination by standardized ELISA and an Opsonophagocytic Assay (OPA. The primary endpoint was the proportion of patients responding to at least 5 of the 7 serotypes by ELISA at one month.At 1 month post vaccination, 12 patients (60% were responders by ELISA, among whom 8 were also responders by OPA. At 6 months, 6 (30% of total of the 12 responders had persistent immunity, and only 2 (10% of total at 12 months. These results suggested a partial response in this population and a rapid decrease in antibody levels in the first months of vaccination.Although one injection of the 13-valent pneumococcal conjugate vaccine is immunogenic in some patients with SMM, the response is transient. Repeated injections are likely to be needed for effective and sustained protection. Keywords: Immunology, Vaccines, Infectious disease
Full Text Available Abstract Background In Australia in June 2001, a unique pneumococcal vaccine schedule commenced for Indigenous infants; seven-valent pneumococcal conjugate vaccine (7PCV given at 2, 4, and 6 months of age and 23-valent pneumococcal polysaccharide vaccine (23PPV at 18 months of age. This study presents carriage serotypes following this schedule. Methods We conducted cross sectional surveys of pneumococcal carriage in Aboriginal children 0 to 6 years of age living in remote Aboriginal communities (RACs in 2003 and 2005. Nasal secretions were collected and processed according to published methods. Results 902 children (mean age 25 months living in 29 communities in 2003 and 818 children (mean age 35 months in 17 communities in 2005 were enrolled. 87% children in 2003 and 96% in 2005 had received two or more doses of 7PCV. From 2003 to 2005, pneumococcal carriage was reduced from 82% to 76% and reductions were apparent in all age groups; 7PCV-type carriage was reduced from 11% to 8%, and 23PPV-non-7PCV-type carriage from 31% to 25% respectively. Thus non-23PPV-type carriage increased from 57% to 67%. All these changes were statistically significant, as were changes for some specific serotypes. Shifts could not be attributed to vaccination alone. The top 10 of 40 serotypes identified were (in descending order 16F, 19A, 11A, 6C, 23B, 19F, 6A, 35B, 6B, 10A and 35B. Carriage of penicillin non-susceptible (MIC > = 0.12 μg/mL strains (15% overall was detected in serotypes (descending order 19A, 19F, 6B, 16F, 11A, 9V, 23B, and in 4 additional serotypes. Carriage of azithromycin resistant (MIC > = 2 μg/mL strains (5% overall, was detected in serotypes (descending order 23B, 17F, 9N, 6B, 6A, 11A, 23F, and in 10 additional serotypes including 6C. Conclusion Pneumococcal carriage remains high (~80% in this vaccinated population. Uptake of both pneumococcal vaccines increased, and carriage was reduced between 2003 and 2005. Predominant serotypes in combined
Silvio D Brugger
Full Text Available Simultaneous carriage of more than one strain of Streptococcus pneumoniae promotes horizontal gene transfer events and may lead to capsule switch and acquisition of antibiotic resistance. We studied the epidemiology of cocolonization with S. pneumoniae before and after introduction of the seven-valent conjugated pneumococcal vaccine (PCV7.Nasopharyngeal swabs (n 1120 were collected from outpatients between 2004 and 2009 within an ongoing nationwide surveillance program. Cocolonization was detected directly from swabs by restriction fragment length polymorphism (RFLP analysis. Serotypes were identified by agglutination, multiplex PCR and microarray.Rate of multiple colonization remained stable up to three years after PCV7 introduction. Cocolonization was associated with serotypes of low carriage prevalence in the prevaccine era. Pneumococcal colonization density was higher in cocolonized samples and cocolonizing strains were present in a balanced ratio (median 1.38. Other characteristics of cocolonization were a higher frequency at young age, but no association with recurrent acute otitis media, recent antibiotic exposure, day care usage and PCV7 vaccination status.Pneumococcal cocolonization is dominated by serotypes of low carriage prevalence in the prevaccine era, which coexist in the nasopharynx. Emergence of such previously rare serotypes under vaccine selection pressure may promote cocolonization in the future.
Sasaki, Atsushi; Kunimoto, Masaru; Takeno, Sachio; Sumiya, Takahiro; Ishino, Takashi; Sugino, Hirotoshi; Hirakawa, Katsuhiro
This study investigated: (i) changes in the incidence of acute otitis media (AOM) following introduction of public funding for free inoculation with 7- and 13-valent pneumococcal conjugate vaccines (PCV7 and PCV13, respectively) and (ii) changes in the rate of myringotomies for AOM (MyfA) in children 1year following the publication of the first edition of the clinical practice guidelines for the diagnosis and management of AOM in children in Japan. PCV7 was launched on the Japanese market in 2010 and gained public funding in 2011. PCV7 was replaced with PCV13 in November 2013. Using the Japan Medical Data Center Claims Database, an 11-year study conducted between January 2005 and December 2015 investigated the decline in the incidence of visits to medical institutions (VtMI) due to all-cause AOM in children <15years. The rate of MyfA from January 2007 to December 2015was also investigated and changes before and after introduction of public funding for PCV7 (pfPCV7) and PCV13 (pfPCV13) for children were examined. Statistical data for the age group between 10 years and <15years served as the control. An analysis was conducted to examine changes for each age group, from infants that had received PCVs to children <5years. Statistical analysis was performed using the chi-square test and Ryan's multiple comparison tests. Ryan's multiple comparison tests were applied at a 5% level of significance. Due to significant changes in the guidelines on the indications for myringotomy introduced in 2013, statistical analysis of the rate of MyfA was limited to the pre- and post-PCV7 period. After introduction of pfPCV7 and pfPCV13, no significant suppression of the incidence of VtMI was observed in any age group. There was a gradual decline in the rate of MyfA after 2011. Compared to the control group, significant differences in all age groups from infants to children <5years were observed (p<0.009, chi-square test). Within 2 years after the introduction of PCV7, a significant
Barington, T; Juul, Lars; Gyhrs, A
The influence of preexisting immunity on the heavy-chain isotypes of circulating antibody-secreting cells (AbSC) induced by vaccination with Haemophilus influenzae type b (Hib) capsular polysaccharide (HibCP) coupled to tetanus toxoid (TT) or diphtheria toxoid (DT) and by vaccination with TT or D...... of natural HibCP antibodies (r = 0.59; P = 0.00002). A possible role of natural exposure for Hib or cross-reactive bacteria on the mucosal surfaces in the shaping of the isotype response to HibCP conjugate vaccines is discussed....
Bahuaud, Mathilde; Bodilis, Hélène; Malphettes, Marion; Maugard Landre, Anaïs; Matondo, Caroline; Bouscary, Didier; Batteux, Frédéric; Launay, Odile; Fermand, Jean-Paul
Smoldering multiple myeloma (SMM) is an asymptomatic clonal plasma cell disorder that frequently progress to multiple myeloma (MM), a disease at high risk of pneumococcal infections. Moreover, if the polysaccharide vaccine is poorly immunogenic in MM, the 13-valent conjugated vaccine has never been tested in clonal plasma cell disorders. We evaluated its immunogenicity for 7 serotypes in 20 patients ≥ 50 years of age with smoldering multiple myeloma (SMM) pre and post routine-vaccination with PCV13. Concentrations of IgG specific for 7 serotypes were measured at baseline, 1, 6, and 12 months after vaccination by standardized ELISA and an Opsonophagocytic Assay (OPA). The primary endpoint was the proportion of patients responding to at least 5 of the 7 serotypes by ELISA at one month. At 1 month post vaccination, 12 patients (60%) were responders by ELISA, among whom 8 were also responders by OPA. At 6 months, 6 (30% of total) of the 12 responders had persistent immunity, and only 2 (10% of total) at 12 months. These results suggested a partial response in this population and a rapid decrease in antibody levels in the first months of vaccination. Although one injection of the 13-valent pneumococcal conjugate vaccine is immunogenic in some patients with SMM, the response is transient. Repeated injections are likely to be needed for effective and sustained protection.
Djingarey, Mamoudou H.; Diomandé, Fabien V. K.; Barry, Rodrigue; Kandolo, Denis; Shirehwa, Florence; Lingani, Clement; Novak, Ryan T.; Tevi-Benissan, Carol; Perea, William; Preziosi, Marie-Pierre; LaForce, F. Marc
Background. A group A meningococcal conjugate vaccine (PsA-TT) was developed specifically for the African “meningitis belt” and was prequalified by the World Health Organization (WHO) in June 2010. The vaccine was first used widely in Burkina Faso, Mali, and Niger in December 2010 with great success. The remaining 23 meningitis belt countries wished to use this new vaccine. Methods. With the help of African countries, WHO developed a prioritization scheme and used or adapted existing immunization guidelines to mount PsA-TT vaccination campaigns. Vaccine requirements were harmonized with the Serum Institute of India, Ltd. Results. Burkina Faso was the first country to fully immunize its 1- to 29-year-old population in December 2010. Over the next 4 years, vaccine coverage was extended to 217 million Africans living in 15 meningitis belt countries. Conclusions. The new group A meningococcal conjugate vaccine was well received, with country coverage rates ranging from 85% to 95%. The rollout proceeded smoothly because countries at highest risk were immunized first while attention was paid to geographic contiguity to maximize herd protection. Community participation was exemplary. PMID:26553672
Silfverdal, Sven Arne; Høgh, Birthe; Bergsaker, Marianne Riise
BACKGROUND: The immunogenicity of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) was determined following a simplified 2-dose priming and the more commonly employed 3-dose priming both followed by a booster dose. METHODS: A total of 351 healthy....... RESULTS: Depending on the serotype, the percentages of subjects reaching the ELISA antibody threshold of 0.2 microg/mL were 92.8% to 98.0% following 2 primary doses and 96.1% to 100% following 3 primary doses except for serotype 6B (55.7% and 63.1%, respectively) and serotype 23F (69.3% and 77...
Sabbatini, Paul J; Ragupathi, Govind; Hood, Chandra
PURPOSE: To characterize the safety and immunogenicity of a heptavalent antigen-keyhole limpet hemocyanin (KLH) plus QS21 vaccine construct in patients with epithelial ovarian, fallopian tube, or peritoneal cancer in second or greater complete clinical remission. EXPERIMENTAL DESIGN: Eleven......). RESULTS: Eleven patients were included in the safety analysis; 9 of 11 patients remained on study for at least 2 weeks past fourth vaccination and were included in the immunologic analysis (two withdrew, disease progression). The vaccine was well tolerated. Self-limited and mild fatigue (maximum grade 2...... patients in this pilot trial received a heptavalent vaccine s.c. containing GM2 (10 microg), Globo-H (10 microg), Lewis Y (10 microg), Tn(c) (3 microg), STn(c) (3 microg), TF(c) (3 microg), and Tn-MUC1 (3 microg) individually conjugated to KLH and mixed with adjuvant QS21(100 microg). Vaccinations were...
Howitz, Michael Frantz; Harboe, Zitta Barrella; Ingels, Helene
Introduction of Pneumococcal Conjugated Vaccines (PCV) in national immunization programs have been successful in reducing the number of invasive and lower respiratory pneumococcal infections. The impact of the vaccines on upper respiratory infections caused by pneumococci is less clear although...... these account for most pneumococcal infections. In this study, we used likely proxies for respiratory infections in children, such as antibiotic use and ventilation tube insertions (VTI), to estimate the impact of the vaccine on a national level. The study was designed as a population-based retrospective...... reversed to near year 2000 levels after the introduction of PCV. This indicates that implementation of pneumococcal vaccines in the Childhood Vaccination Programme has likely reduced the incidence of upper respiratory diseases due to pneumococci in Denmark....
Ana Cristina Cisne Frota
Conclusion: Seroprotection at 12–18 months after single dose of MCC was low for both groups, and higher among individuals who presented baseline immunity. Among HIVI, vaccine should be administered after UVL is achieved.
González Martínez, F; Navarro Gómez, M L; Saavedra Lozano, J; Santos Sebastián, M M; Rodríguez Fernández, R; González Sanchéz, M; Cercenado Mansilla, E; Hernández-Sampelayo Matos, T
There has been an increased incidence in invasive pneumococcal disease (IPD) produced by non-vaccine serotype (NVS) of Streptococcus pneumoniae after the introduction of PCV7. Our objective was to describe the epidemiological, clinical and microbiological characteristics of IPD caused by NVS in a tertiary hospital in Madrid. Retrospective (1998-2004) and prospective (2005-2009) study evaluating IPD caused by NVS in children. The study was divided into three periods: P1 (1998-2001) when PCV7 was not commercialized; P2 (2002-2005) with 40% vaccine coverage among children; and P3 (2006-2009) when the vaccine was added to the Childhood Immunization Schedule in Madrid. We analyzed 155 cases of IPD. One hundred and fifty of these isolates were serotyped (100 were NVS). There was an increase in the prevalence of IPD from P1 (31%) to P2 (54%) and P3 (91%). The most relevant emerging serotypes were 19A, 7F, 1, 5, 3 and 15C. The most significant clinical syndromes produced by some specific serotypes were as follows: lower respiratory tract infection (LRTI) by serotypes 1, 3, 5 and 15C; LRTI, primary bacteremia and meningitis by serotype 19A; and primary bacteremia by serotype 7F (66%). The large majority (83.8%) of NVS were sensitive to penicillin. There has been an increased prevalence of IPD caused by NVS since the introduction of PCV7. These changes should prompt the introduction of new pneumococcal vaccines, which include most of the NVS, in the childhood immunization calendar to prevent IPD in children. Copyright © 2012 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.
Wasserman, Matt; Wilson, Michele; McDade, Cheryl; Grajales, Ana Gabriela; Palacios, Maria Gabriela; Baez- Revueltas, Fabiola Berenice; Farkouh, Raymond
Abstract Background PCV13 replaced 7-valent pneumococcal conjugate vaccine in the routine infant immunization schedule in Mexico since 2011. The use of PCV13 has reduced pneumococcal disease incidence for vaccine serotypes, particularly 19A, which emerged following PCV7 use. The 10-valent vaccine (PCV10) contains the same serotypes as PCV13 with the exception of serotypes 3, 19A and 6A but also has different conjugated proteins for the common serotypes. This study evaluated the potential health and economic implications of switching from PCV13 to PCV10 in Mexico. Methods A decision-analytic model was developed to estimate public health and economic impact of maintaining PCV13 compared with switching to PCV10 in Mexico. Disease incidence at time of potential switch for invasive pneumococcal disease (IPD), pneumonia (PNE) and acute otitis media (AOM) was obtained from Dirección General de Epidemiología and the published literature. Historical data was used to estimate IPD trends under different infant vaccine pressures and the model forecasted disease across the population. For each vaccination program, health outcomes and associated health-care costs were estimated. Costs, utility weights, and risk of disease-specific complications were derived from published sources. Results In the base case, continued use of PCV13 would result in significantly fewer cases of pneumococcal disease than switching to PCV10 in Mexico (See Table 1). Despite a higher vaccine cost, PCV13 was cost-saving compared with PCV10 in the base case and across a number of scenarios evaluated. Table 1: Total cases and costs associated with maintaining use of PCV13 vs. switching to PCV10 in Mexico over a 10 year period PCV13 PCV10 Difference IPD 16,808 17,248 −440 AOM 7,023,448 7,245,446 −221,998 PNE 1,743,115 1,831,936 −88,821 Deaths 19,457 19,867 −410 Total QALYs 864,069,669 864,068,101 1,568 Total Cost $258,353,508,707 $264,927,566,637 −$6,574,057,930 ICER PCV13 Dominant Costs are
Full Text Available Background: Regarding risk of bacterial meningitis (BM after Cochlear implantation (CI, it was suggested to receive polyvalent conjugate vaccine. We aimed to estimate the prevalence of BM post CI in child recipients who do not receive polyvalent vaccine. Methods: We enrolled 371 children who had received cochlear implants from 2007 to 2010. None of them received pre or post implantation polyvalent conjugate vaccine for BM. We followed all of them for BM for 2 years after implantation. Results: We detected only one female case of BM (0.3% of patients with the age of 24 months. The mean age of noninfected children was 36.7 ± 23.2 months. The education level of parents was "college level or higher" in less than half of them, and about 65% of patients were products of consanguineous marriage. Conclusions: Our findings indicated that the incidence of BM was not higher in our cochlear implanted children who did not receive immunization than patients from countries in which routine vaccination is done. We suggest that although proper immunization is recommended before surgery, this procedure could be performed without vaccination, especially in developing countries that face financial problems for preparing vaccines.
ASSESSMENT OF TOLERABILITY OF PNEUMOCOCCAL CONJUGATE VACCINE AND THE INFLUENCE OF THE VACCINATION ON THE INCIDENCE OF RESPIRATORY INFECTIONS IN CHILDREN DURING THE FIRST FIVE YEARS OF LIFE IN THE SAKHA REPUBLIC (YAKUTIA
Full Text Available One of the most frequent etiology agent of upper respiratory tract infection is pneumococcus. Most susceptible to this infection are children under 5 years old. It is known that the only effective prevention of pneumococcal infections is a specific immunoprophylaxis. Authors represent their own experience of vaccination for the child population at risk. The analysis of the effectiveness of 7-valent conjugate pneumococcal vaccine in 596 children under 5 years old is demonstrated. The immunization is revealed low reactogeni city of vaccine and evident clinical effect. Thus, this vaccine may be recommended for inclusion in a regional immunization schedule in Republic of Sakha (Yakutia.Key words: children, pneumococcal infection, vaccine prophylaxis.
Jahouh, Farid; Hou, Shu-jie; Kováč, Pavol; Banoub, Joseph H.
RATIONALE Neoglycoconjugate vaccines synthesized by the squaric acid spacer method allow single point attachment of the carbohydrate antigen to the protein carrier. However, the localization of the carbohydrate antigen sites of conjugation on the protein carrier has been an elusive task difficult to achieve. METHOD Covalent attachment of the lactose antigen to the bovine serum albumin (BSA) was prepared by the squaric acid method using a hapten:BSA ratio of 20:1. Different reaction times were used during the conjugation reaction and two different lactose-BSA glycoconjugate vaccines were obtained. The carbohydrate antigen hapten:BSA ratios of these lactose-BSA glycoconjugate vaccines were determined by MALDI-TOF/RTOF-MS and the glycation sites in the neoglycoconjugates were determined using nano-LC/ESI-QqTOF-MS/MS analysis of the trypsin and GluC V8 digests of the conjugates. RESULTS We have identified a total of 15 glycation sites located on the BSA lysine residues for the neoglycoconjugate vaccine formed with a hapten:BSA ratio of 5.1:1, However, the tryptic and GluC V8 digests of the hapten-BSA glycoconjugate with a hapten:BSA ratio of 19.0:1 allowed identification of 30 glycation sites located on the BSA. These last results seem to indicate that this conjugation results in formation of various glycoforms. CONCLUSIONS It was observed that the number of identified glycation sites increased when the hapten:BSA ratio of glycoconjugate formation increased, and that the location of the glycation sites appears to be mainly on the outer surface of the BSA carrier molecule which is in line with the assumption that the sterically more accessible lysine residues, namely those located on the outer surface of the BSA, would be conjugated preferentially. PMID:22368054
Newall, A T; Reyes, J F; McIntyre, P; Menzies, R; Beutels, P; Wood, J G
Retrospective cost-effectiveness analyses of vaccination programs using routinely collected post-implementation data are sparse by comparison with pre-program analyses. We performed a retrospective economic evaluation of the childhood 7-valent pneumococcal conjugate vaccine (PCV7) program in Australia. We developed a deterministic multi-compartment model that describes health states related to invasive and non-invasive pneumococcal disease. Costs (Australian dollars, A$) and health effects (quality-adjusted life years, QALYs) were attached to model states. The perspective for costs was that of the healthcare system and government. Where possible, we used observed changes in the disease rates from national surveillance and healthcare databases to estimate the impact of the PCV7 program (2005-2010). We stratified our cost-effectiveness results into alternative scenarios which differed by the outcome states included. Parameter uncertainty was explored using probabilistic sensitivity analysis. The PCV7 program was estimated to have prevented ∼5900 hospitalisations and ∼160 deaths from invasive pneumococcal disease (IPD). Approximately half of these were prevented in adults via herd protection. The incremental cost-effectiveness ratio was ∼A$161,000 per QALY gained when including only IPD-related outcomes. The cost-effectiveness of PCV7 remained in the range A$88,000-$122,000 when changes in various non-invasive disease states were included. The inclusion of observed changes in adult non-invasive pneumonia deaths substantially improved cost-effectiveness (∼A$9000 per QALY gained). Using the initial vaccine price negotiated for Australia, the PCV7 program was unlikely to have been cost-effective (at conventional thresholds) unless observed reductions in non-invasive pneumonia deaths in the elderly are attributed to it. Further analyses are required to explore this finding, which has significant implications for the incremental benefit achievable by adult PCV
Cho, Ying-Chun; Chiu, Nan-Chang; Lu, Chun-Yi; Huang, Daniel Tsung-Ning; Huang, Fu-Yuan; Chang, Luan-Yin; Huang, Li-Min; Chi, Hsin
After the introduction of 13-valent pneumococcal conjugate vaccine (PCV13) against Streptococcus pneumoniae, public health officials in Taiwan monitored a decline in circulating vaccine serotypes and the emergence of nonvaccine serotypes in children with invasive pneumococcal disease. A gradually expanded PCV13 national immunization program was launched in 2013 in Taiwan. Here, we evaluate the changes in the distribution of pneumococcal serotypes and antimicrobial nonsusceptibility in children during the evolution of vaccination policy. S. pneumoniae isolates from children with pneumococcal disease were collected and serotyped from 2010 to 2015 in northern Taiwan. PCVs were administered at the recipients' expense between 2010 and 2012, and then PCV13 was partially reimbursed by the government beginning in 2013. The distribution and diversity of serotypes were analyzed along with their antimicrobial susceptibilities. Among a total of 498 isolates, the proportion of invasive pneumococcal disease isolates declined (47.1%-10.6%) during the study period, and serotype diversity increased after 2011. Between 2010 and 2012, the dominant serotypes were 19A, 19F, 3, 6B and 14, and serotype 19A rose from 44.1% to 57.5%. Serotypes 19A, 15A, 19F and 15B were more prevalent from 2013 to 2015, and serotype 19A decreased from 42.1% to 4.5%. Serotypes 19F and 15A became the most commonly detected serotypes in 2015. Overall, PCV13 additional serotypes were reduced by 80% (P program is effective against pneumococcal disease in Taiwanese children, mainly by reducing PCV13 additional serotypes.
van Damme, Pierre; Kafeja, Froukje; Anemona, Alessandra; Basile, Venere; Hilbert, Anne Katrin; De Coster, Ilse; Rondini, Simona; Micoli, Francesca; Qasim Khan, Rana M; Marchetti, Elisa; Di Cioccio, Vito; Saul, Allan; Martin, Laura B; Podda, Audino
Typhoid fever causes more than 21 million cases of disease and 200,000 deaths yearly worldwide, with more than 90% of the disease burden being reported from Asia. Epidemiological data show high disease incidence in young children and suggest that immunization programs should target children below two years of age: this is not possible with available vaccines. The Novartis Vaccines Institute for Global Health developed a conjugate vaccine (Vi-CRM₁₉₇) for infant vaccination concomitantly with EPI vaccines, either starting at 6 weeks with DTP or at 9 months with measles vaccine. We report the results from a Phase 1 and a Phase 2 dose ranging trial with Vi-CRM₁₉₇ in European adults. Following randomized blinded comparison of single vaccination with either Vi-CRM₁₉₇ or licensed polysaccharide vaccines (both containing 25·0 µg of Vi antigen), a randomised observer blinded dose ranging trial was performed in the same center to compare three concentrations of Vi-CRM₁₉₇ (1·25 µg, 5·0 µg and 12·5 µg of Vi antigen) with the polysaccharide vaccine. All vaccines were well tolerated. Compared to the polysaccharide vaccine, Vi-CRM₁₉₇ induced a higher incidence of mild to moderate short lasting local pain. All Vi-CRM₁₉₇ formulations induced higher Vi antibody levels compared to licensed control, with clear dose response relationship. Vi-CRM₁₉₇ did not elicit safety concerns, was highly immunogenic and is therefore suitable for further clinical testing in endemic populations of South Asia. ClinicalTrials.gov NCT01123941 NCT01193907.
Pierre van Damme
Full Text Available Typhoid fever causes more than 21 million cases of disease and 200,000 deaths yearly worldwide, with more than 90% of the disease burden being reported from Asia. Epidemiological data show high disease incidence in young children and suggest that immunization programs should target children below two years of age: this is not possible with available vaccines. The Novartis Vaccines Institute for Global Health developed a conjugate vaccine (Vi-CRM₁₉₇ for infant vaccination concomitantly with EPI vaccines, either starting at 6 weeks with DTP or at 9 months with measles vaccine. We report the results from a Phase 1 and a Phase 2 dose ranging trial with Vi-CRM₁₉₇ in European adults.Following randomized blinded comparison of single vaccination with either Vi-CRM₁₉₇ or licensed polysaccharide vaccines (both containing 25·0 µg of Vi antigen, a randomised observer blinded dose ranging trial was performed in the same center to compare three concentrations of Vi-CRM₁₉₇ (1·25 µg, 5·0 µg and 12·5 µg of Vi antigen with the polysaccharide vaccine.All vaccines were well tolerated. Compared to the polysaccharide vaccine, Vi-CRM₁₉₇ induced a higher incidence of mild to moderate short lasting local pain. All Vi-CRM₁₉₇ formulations induced higher Vi antibody levels compared to licensed control, with clear dose response relationship.Vi-CRM₁₉₇ did not elicit safety concerns, was highly immunogenic and is therefore suitable for further clinical testing in endemic populations of South Asia.ClinicalTrials.gov NCT01123941 NCT01193907.
Daniel R Feikin
Full Text Available BACKGROUND: Vaccine-serotype (VT invasive pneumococcal disease (IPD rates declined substantially following introduction of 7-valent pneumococcal conjugate vaccine (PCV7 into national immunization programs. Increases in non-vaccine-serotype (NVT IPD rates occurred in some sites, presumably representing serotype replacement. We used a standardized approach to describe serotype-specific IPD changes among multiple sites after PCV7 introduction. METHODS AND FINDINGS: Of 32 IPD surveillance datasets received, we identified 21 eligible databases with rate data ≥ 2 years before and ≥ 1 year after PCV7 introduction. Expected annual rates of IPD absent PCV7 introduction were estimated by extrapolation using either Poisson regression modeling of pre-PCV7 rates or averaging pre-PCV7 rates. To estimate whether changes in rates had occurred following PCV7 introduction, we calculated site specific rate ratios by dividing observed by expected IPD rates for each post-PCV7 year. We calculated summary rate ratios (RRs using random effects meta-analysis. For children <5 years old, overall IPD decreased by year 1 post-PCV7 (RR 0.55, 95% CI 0.46-0.65 and remained relatively stable through year 7 (RR 0.49, 95% CI 0.35-0.68. Point estimates for VT IPD decreased annually through year 7 (RR 0.03, 95% CI 0.01-0.10, while NVT IPD increased (year 7 RR 2.81, 95% CI 2.12-3.71. Among adults, decreases in overall IPD also occurred but were smaller and more variable by site than among children. At year 7 after introduction, significant reductions were observed (18-49 year-olds [RR 0.52, 95% CI 0.29-0.91], 50-64 year-olds [RR 0.84, 95% CI 0.77-0.93], and ≥ 65 year-olds [RR 0.74, 95% CI 0.58-0.95]. CONCLUSIONS: Consistent and significant decreases in both overall and VT IPD in children occurred quickly and were sustained for 7 years after PCV7 introduction, supporting use of PCVs. Increases in NVT IPD occurred in most sites, with variable magnitude. These findings may not
Full Text Available In Italy, the effectiveness of pneumococcal universal vaccination in preventing vaccine-type invasive pneumococcal disease (IPD in the PCV7/PCV13 shifting period was estimated to be 84.3% (95% CI: 84.0–84.6% in children <5 years. This study aims at corroborating the estimation of both the effectiveness (VE of PCVs and its impact in reducing pneumococcal diseases. A 1 : 3 matched-case-control study was conducted among children <5 years old hospitalized for IPD or pneumococcal pneumonia (PP between 2006 and 2012 in the Puglia region. Moreover, hospitalizations for pneumococcal outcomes in the pre- and postvaccination period and the hospitalization risk ratios (HRRs with 95% CIs were computed in Italy and in the first eight regions that introduced PCVs in 2006. The overall effectiveness of PCVs was 75% (95% CI: 61%–84%; it was 69% (95% CI: 30%–88% against IPD and 77% (95% CI: 61%–87% against PP. PCVs showed a significant impact on IPD and acute otitis media either at a national level or in those regions with a longer vaccination history, with a nearly 40% reduction of hospitalizations for both outcomes. Our findings provide further evidence of the effectiveness of PCVs against pneumococcal diseases and its impact on nasopharyngeal carriage in children <5 years, indicating the importance of maintaining high immunization coverage.
Wessels, M R; Paoletti, L C; Rodewald, A K; Michon, F; DiFabio, J; Jennings, H J; Kasper, D L
Antisera elicited by type Ia group B streptococci (GBS) contain antibodies that react with both type Ia and type Ib strains. Previous studies suggested that antibodies elicited by type Ia organisms recognized a carbohydrate antigen or epitope common to Ia and Ib strains. We now report the synthesis and immunogenicity testing of a type Ia polysaccharide-tetanus toxoid (Ia-TT) conjugate vaccine. Ia-TT elicited type Ia polysaccharide-specific immunoglobulin G antibodies in all three of the rabbi...
Wu, David Bin-Chia; Chaiyakunapruk, Nathorn; Chong, Huey-Yi; Beutels, Philippe
Seven-valent pneumococcal conjugate vaccines (PCV7) have been used in children for more than a decade. Given the observed increase in disease caused by pneumococcal serotypes not covered by PCV7, an increasing number of countries are switching from 7-valent to 10- and 13-valent PCVs ("PCV10" and "PCV13"). Economic evaluations are important tools to inform decisions and price negotiations to make such a switch. This review aims to provide a critical assessment of economic evaluations involving PCV10 or PCV13, published since 2006. We searched Scopus, ISI Web of Science (SCI and SSCI) and Pubmed to retrieve, select and review relevant studies, which were archived between 1st January 2006 and 31st January 2014. The review protocol involved standard extraction of assumptions, methods, results and sponsorships from the original studies. Sixty-three economic evaluations on PCVs published since January 2006 were identified. About half of these evaluated PCV10 and/or PCV13, the subject of this review. At current prices, both PCV13 and PCV10 were likely judged preferable to PCV7. However, the combined uncertainty related to price differences, burden of disease, vaccine effectiveness, herd and serotype replacement effects determine the preference base for either PCV10 or PCV13. The pivotal assumptions and results of these analyses also depended on which manufacturer sponsored the study. A more thorough exploration of uncertainty should be made in future analyses on this subject, as we lack understanding to adequately model herd and serotype replacement effects to reliably predict the population impact of PCVs. The introduction of further improved PCVs in an environment of evolving antibiotic resistance and under the continuing influence of previous PCVs implies that the complexity and data requirements for relevant analyses will further increase. Decision makers using these analyses should not just rely on an analysis from a single manufacturer. Copyright © 2015 Elsevier
Full Text Available Pneumonia is the major cause of death in children globally, with more than 900,000 deaths annually in children under five years of age. Streptococcus pneumoniae causes most deaths, most often in the form of community acquired pneumonia. Pneumococcal conjugate vaccines (PCVs are currently being implemented in many low-income countries. PCVs decrease vaccine-type pneumococcal carriage, a prerequisite for invasive pneumococcal disease, and thereby affects pneumococcal disease and transmission. In Uganda, PCV was launched in 2014, but baseline data is lacking for pneumococcal serotypes in carriage.To study pneumococcal nasopharyngeal carriage and serotype distribution in children under 5 years of age prior to PCV introduction in Uganda.Three cross-sectional pneumococcal carriage surveys were conducted in 2008, 2009 and 2011, comprising respectively 150, 587 and 1024 randomly selected children aged less than five years from the Iganga/Mayuge Health and Demographic Surveillance Site. The caretakers were interviewed about illness history of the child and 1723 nasopharyngeal specimens were collected. From these, 927 isolates of S. pneumoniae were serotyped.Overall, the carriage rate of S. pneumoniae was 56% (957/1723. Pneumococcal carriage was associated with illness on the day of the interview (OR = 1.50, p = 0.04. The most common pneumococcal serotypes were in descending order 19F (16%, 23F (9%, 6A (8%, 29 (7% and 6B (7%. One percent of the strains were non-typeable. The potential serotype coverage rate for PCV10 was 42% and 54% for PCV13.About half of circulating pneumococcal serotypes in carriage in the Ugandan under-five population studied was covered by available PCVs.
Tinevimbo Shiri, DrPhD
Full Text Available Summary: Background: The full extent to which childhood pneumococcal conjugate vaccines (PCV can indirectly reduce illness in unvaccinated populations is not known. We aimed to estimate the magnitude and timing of indirect effects of PCVs on invasive pneumococcal disease. Methods: In this systematic review and meta-analysis, we searched bibliographic databases for non-randomised quasi-experimental or observational studies reporting invasive pneumococcal disease changes following PCV introduction in unvaccinated populations (studies published Sept 1, 2010, to Jan 6, 2016, updating the previous systematic review of the same topic (studies published Jan 1, 1994, to Sept 30, 2010. Two reviewers extracted summary data by consensus. We used a Bayesian mixed-effects model to account for between-study heterogeneity to estimate temporal indirect effects by pooling of invasive pneumococcal disease changes by serotype and serogroup. Findings: Data were extracted from 70 studies included in the previous review and 172 additional studies, covering 27 high-income and seven middle-income countries. The predicted mean times to attaining a 90% reduction in invasive pneumococcal disease were 8·9 years (95% credible interval [CrI] 7·8–10·3 for grouped serotypes contained in the seven-valent PCV (PCV7, and 9·5 years (6·1–16·6 for the grouped six additional serotypes contained in the 13-valent PCV (PCV13 but not in PCV7. Disease due to grouped serotypes contained in the 23-valent pneumococcal polysaccharide vaccine (PPV23 decreased at similar rates per year in adults aged 19–64 years (relative risk [RR] 0·85, 95% CrI 0·75–0·95 and 65 years and older (0·87, 0·84–0·90. However, we noted no changes in either group in invasive pneumococcal disease caused by the additional 11 serotypes covered by PPV23 but not PCV13. Interpretation: Population childhood PCV programmes will lead, on average, to substantial protection across the whole population
Full Text Available Abstract Background Medical and public health importance of pneumococcal infections justifies the implementation of measures capable of reducing their incidence and severity, and explains why the recently marketed heptavalent pneumococcal conjugate vaccine (PCV-7 has been widely studied by pediatricians. This study was designed to evaluate the impact of PCV-7 administered at 3, 5 and 11 months of age on respiratory tract infections in very young children. Methods A total of 1,571 healthy infants (910 males aged 75–105 days (median 82 days were enrolled in this prospective cohort trial to receive a hexavalent vaccine (DTaP/IPV/HBV/Hib and PCV-7 (n = 819 or the hexavalent vaccine alone (n = 752 at 3, 5 and 11 months of age. Morbidity was recorded for the 24 months following the second dose by monthly telephone interviews conducted by investigators blinded to the study treatment assignment using standardised questionnaires. During these interviews, the caregivers and the children's pediatricians were questioned about illnesses and the use of antibiotics since the previous telephone call. All of the data were analysed using SAS Windows v.12. Results Among the 1,555 subjects (98.9% who completed the study, analysis of the data by the periods of follow-up demonstrated that radiologically confirmed community-acquired pneumonia (CAP was significantly less frequent in the PCV-7 group during the follow-up as a whole and during the last period of follow-up. Moreover, there were statistically significant between-group differences in the incidence of acute otitis media (AOM in each half-year period of follow-up except the first, with significantly lower number of episodes in children receiving PCV-7 than in controls. Furthermore, the antibiotic prescription data showed that the probability of receiving an antibiotic course was significantly lower in the PCV-7 group than in the control group. Conclusion Our findings show the effectiveness of the simplified
Mitra, Monjori; Shah, Nitin; Ghosh, Apurba; Chatterjee, Suparna; Kaur, Iqbal; Bhattacharya, Nisha; Basu, Suparna
Vi polysaccharide typhoid vaccines cannot be used in children vaccine prepared by binding Vi to tetanus toxoids (Vi-TT) induces protective levels even in children safety following vaccination with a Vi-TT vaccine in children 6 months to 12 years of age. Overall, 1765 subjects were recruited from two registered municipal urban slums of southern Kolkata. Most of the children of the slum dwellers attended the schools in the locality which was selected with permission from the school authority. Schools were randomly divided into vaccinated (Test group) and unvaccinated group (Control group). Children and their siblings of test group received 2-doses of PedaTyph™ vaccine at 6 weeks interval. Control group received vaccines as per national guidelines. Adverse events (AEs) were examined after 30 minutes, 1 month and clinical events were observed till 12 months post-vaccination. Incidence of culture positive typhoid fever in the control group was 1.27% vis-a-vis none in vaccine group during 12 months. In subgroup evaluated for immunogenicity, an antibody titer value of 1.8 EU/ml (95% CI: 1.5 EU/ml, 2.2 EU/ml), 32 EU/ml (95% CI: 27.0 EU/ml, 39.0 EU/ml) and 14 EU/ml (95% CI: 12.0 EU/ml, 17.0 EU/ml) at baseline, 6 weeks and 12 months, respectively was observed. Sero-conversion among the sub-group was 100% after 6 weeks of post-vaccination and 83% after 12 months considering 4-fold rise from baseline. The efficacy of vaccine was 100 % (95% CI: 97.6%, 100%) in the first year of follow-up with minimal AEs post vaccination. Vi conjugate typhoid vaccine conferred 100% protection against typhoid fever in 1765 children 6 months to 12 years of age with high immunogenicity in a subgroup from the vaccine arm.
Madhi, Shabir A; Kuwanda, Locadiah; Saarinen, Leena; Cutland, Clare; Mothupi, Rosalia; Käyhty, Helena; Klugman, Keith P
The quantitative (anti-Hib capsular polysaccharide antibody concentrations; anti-HibPS) and qualitative (bactericidal activity and avidity) aspects in immune responses to Haemophilus influenzae type b polyribosyl ribitol phospshate-CRM(197) conjugate vaccine (HibCV; HibTiter) were evaluated in 66 HIV infected children not receiving anti-retroviral therapy and 127 HIV uninfected children. Surveillance was conducted for invasive Hib disease in a cohort of 39,865 (approximately 6.4% of whom were HIV infected) children from March 1998 to June 2004. HIV infected children had lower anti-HibPS geometric mean antibody concentrations 1 month post-immunisation than HIV uninfected children (Por=1.0 microg/ml (RR 0.54; 95% CI 0.43-0.69). A lower proportion of HIV infected children than HIV uninfected children (RR 0.78; 95% CI 0.66-0.93) had measurable anti-Hib serum bactericidal activity (SBA) and the HibPS antibody concentration required for 50% killing of Hib bacteria was greater among HIV infected than HIV uninfected children (P=0.001). The estimated risk of HibCV failure was 35.1-fold greater (95% CI 14.6-84.6) amongst HIV infected than HIV uninfected children.
Van Den Bergh, Menno R.; Spijkerman, Judith; François, Nancy; Swinnen, Kristien; Borys, Dorota; Schuerman, Lode; Veenhoven, Reinier H.; Sanders, Elisabeth A M
Background: Immune responses and safety profiles may be affected when vaccines are coadministered. We evaluated the immunogenicity, safety and reactogenicity of a booster dose of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D-conjugate (PHiD-CV; Synflorix GSK Vaccines) and
Full Text Available One of the challenging issues in vaccine development is peptide and adjuvant delivery into target cells. In this study, we developed a vaccine and therapeutic delivery system to increase cytotoxic T lymphocyte (CTL response against a breast cancer model overexpressing HER2/neu. Gp2, a HER2/neu-derived peptide, was conjugated to Maleimide-mPEG2000-DSPE micelles and post inserted into liposomes composed of DMPC, DMPG phospholipids, and fusogenic lipid dioleoylphosphatidylethanolamine (DOPE containing monophosphoryl lipid A (MPL adjuvant (DMPC-DMPG-DOPE-MPL-Gp2. BALB/c mice were immunized with different formulations and the immune response was evaluated in vitro and in vivo. ELISpot and intracellular cytokine analysis by flow cytometry showed that the mice vaccinated with Lip-DOPE-MPL-GP2 incited the highest number of IFN-γ+ in CD8+ cells and CTL response. The immunization led to lower tumor sizes and longer survival time compared to the other groups of mice immunized and treated with the Lip-DOPE-MPL-GP2 formulation in both prophylactic and therapeutic experiments. These results showed that co-formulation of DOPE and MPL conjugated with GP2 peptide not only induces high antitumor immunity but also enhances therapeutic efficacy in TUBO mice model. Lip-DOPE-MPL-GP2 formulation could be a promising vaccine and a therapeutic delivery system against HER2 positive cancers and merits further investigation.
Shariat, Sheida; Badiee, Ali; Jalali, Seyed Amir; Mansourian, Mercedeh; Yazdani, Mona; Mortazavi, Seyed Alireza; Jaafari, Mahmoud Reza
Vaccines containing synthetic peptides derived from tumor-associated antigens (TAA) can elicit potent cytotoxic T lymphocyte (CTL) response if they are formulated in an optimal vaccine delivery system. The aim of this study was to develop a simple and effective lipid-based vaccine delivery system using P5 HER2/neu-derived peptide conjugated to Maleimide-PEG2000-DSPE. The conjugated lipid was then incorporated into liposomes composed of DMPC:DMPG:Chol:DOPE containing Monophosphoryl lipid A (MPL) (Lip-DOPE-P5-MPL). Different liposome formulations were prepared and characterized for their physicochemical properties. To evaluate anti-tumoral efficacy, BALB/c mice were immunized subcutaneously 3 times in two-week intervals and the generated immune response was studied. The results demonstrated that Lip-DOPE-P5-MPL induced a significantly higher IFN-γ production by CD8+ T cells intracellularly which represents higher CTL response in comparison with other control formulations. CTL response induced by this formulation caused the lowest tumor size and the longest survival time in a mice model of TUBO tumor. The encouraging results achieved by Lip-DOPE-P5-MPL formulation could make it a promising candidate in developing effective vaccines against Her2 positive breast cancers. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
Wang, Zhiguo; Ma, Fubao; Zhang, Jinlin; Yu, Jing; Kang, Guodong; Gao, Jun
To analyze the occurrence feature of adverse events following immunization (AEFI) of Hib conjugate vaccine (HibCV) and to evaluate the safety of HibCV in postmarketing. 2008-2013 HibCV AEFI data were collected through national AEFI information management system, which were downloaded in March 18, 2014.The demographic information and inoculation quantity of HibCV were from Immunization information management system in Jiangsu province. The incidence rate and 95% CI value of AEFI, common vaccine reaction and rare vaccine reaction following immunization of HibCV were calculated. The differences in the incidence rate of common vaccine reaction and rare vaccine reaction among sex, months of age, and number of injections were compared by means of (χ² tests. A total of 6.16 million doses of vaccine were administered in Jiangsu province during 2008-2013, and 4 718 vaccinees reported having adverse event, for a rate of 76.60/100 000 (95% CI: 74.42/100 000-78.79/100 000). The incidence rate of common vaccine reaction and rare vaccine reaction was 71.10/100 000 (95% CI: 68.99/100 000-73.20/100 000) and 5.16/100 000 (95% CI: 4.60/100 000-5.73/100 000), respectively. The main symptoms of common vaccine reactions were fever, swelling, indurations and gastrointestinal reactions. The incidence rates of them were 40.54/100 000, 35.09/100 000, 12.94/100 000 and 0.36/100 000 in turn. The main symptoms of rare vaccine reactions were anaphylactic rashes and angioedema, the incidence rates of which were 4.77/100 000 and 0.15/100 000 respectively. 91.39% (4 002/4 379) of common vaccine reactions and 88.36% (281/318) of rare vaccine reactions happened within 1 d after vaccination. Anaphylactic shock (3 cases) and laryngeal edema (1 case) all happened within 1 d after vaccination. The incidence rate of common vaccine reactions among boys (79.72/100 000, 2 641/3 313 071) was higher than that of girls (61.07/100 000, 1 738/2 846 001) (χ² = 74.92, P < 0.001). The incidence rate of common
Burton, Deron C.; Bigogo, Godfrey M.; Audi, Allan O.; Williamson, John; Munge, Kenneth; Wafula, Jackline; Ouma, Dominic; Khagayi, Sammy; Mugoya, Isaac; Mburu, James; Muema, Shadrack; Bauni, Evasius; Bwanaali, Tahreni; Feikin, Daniel R.; Ochieng, Peter M.; Mogeni, Ondari D.; Otieno, George A.; Olack, Beatrice; Kamau, Tatu; Van Dyke, Melissa K.; Chen, Robert; Farrington, Paddy; Montgomery, Joel M.; Breiman, Robert F.; Scott, J. Anthony G.; Laserson, Kayla F.
There is a theoretical risk of adverse events following immunization with a preservative-free, 2-dose vial formulation of 10-valent-pneumococcal conjugate vaccine (PCV10). We set out to measure this risk. Four population-based surveillance sites in Kenya (total annual birth cohort of 11,500 infants) were used to conduct a 2-year post-introduction vaccine safety study of PCV10. Injection-site abscesses occurring within 7 days following vaccine administration were clinically diagnosed in all study sites (passive facility-based surveillance) and, also, detected by caregiver-reported symptoms of swelling plus discharge in two sites (active household-based surveillance). Abscess risk was expressed as the number of abscesses per 100,000 injections and was compared for the second vs first vial dose of PCV10 and for PCV10 vs pentavalent vaccine (comparator). A total of 58,288 PCV10 injections were recorded, including 24,054 and 19,702 identified as first and second vial doses, respectively (14,532 unknown vial dose). The risk ratio for abscess following injection with the second (41 per 100,000) vs first (33 per 100,000) vial dose of PCV10 was 1.22 (95% confidence interval [CI] 0.37–4.06). The comparator vaccine was changed from a 2-dose to 10-dose presentation midway through the study. The matched odds ratios for abscess following PCV10 were 1.00 (95% CI 0.12–8.56) and 0.27 (95% CI 0.14–0.54) when compared to the 2-dose and 10-dose pentavalent vaccine presentations, respectively. In Kenya immunization with PCV10 was not associated with an increased risk of injection site abscess, providing confidence that the vaccine may be safely used in Africa. The relatively higher risk of abscess following the 10-dose presentation of pentavalent vaccine merits further study. PMID:26509274
Harjaningrum, Agnes Tri; Kartasasmita, Cissy; Orne-Gliemann, Joanna; Jutand, Marthe-Aline; Goujon, Nicolas; Koeck, Jean-Louis
Due to the high burden of pneumonia in Indonesia, the inclusion of pneumococcal conjugate vaccine (PCV) into Indonesia's National Immunization Program (NIP) is recommended by World Health Organization. Prior to the introduction of new vaccines, it is imperative to assess the perceptions of the public and medical community about the disease and the vaccine. The purpose of this qualitative study was to explore the knowledge, perceptions, and attitudes of mothers and health care providers (HCPs) toward PCV in Bandung, West Java, Indonesia. Fifty-five respondents (26 mothers and 29 HCPs) were interviewed at public and private health care facilities in Bandung using semi-structured interviews in May-June 2011. Data were analyzed manually according to pre-defined themes. Although most mothers had low knowledge about PCV, did not perceive themselves as susceptible to the disease, perceived that cost was the main barrier to PCV access, and obtained little information on PCV, they considered pneumonia as a severe disease and a priority health problem, perceived benefits of the vaccine, and were likely to adopt it. Similarly, knowledge about PCV among most HCPs was limited. Despite perceiving cost as the main barrier, most HCPs perceived benefits of the vaccine, susceptibility and severity of the disease, regarded pneumonia as a priority health problem, and were likely to suggest the new vaccination. Despite the poor knowledge of mothers and HCPs about PCV, they are aware of the high burden of pneumonia and the need for a vaccine in the NIP. Perceived severity and benefits among mothers, and, additionally, perceived susceptibility among HCPs were manifested in the willingness to accept PCV. The findings would contribute to better understanding the factors, which could support decision-making about vaccine introduction, and be utilized for developing suitable messages for mothers and HCPs. Copyright © 2013 Elsevier Ltd. All rights reserved.
William S Pomat
Full Text Available Approximately 826,000 children, mostly young infants, die annually from invasive pneumococcal disease. A 6-10-14-week schedule of pneumococcal conjugate vaccine (PCV is efficacious but neonatal PCV may provide earlier protection and better coverage. We conducted an open randomized controlled trial in Papua New Guinea to compare safety, immunogenicity and priming for memory of 7-valent PCV (PCV7 given in a 0-1-2-month (neonatal schedule with that of the routine 1-2-3-month (infant schedule.We randomized 318 infants at birth to receive PCV7 in the neonatal or infant schedule or no PCV7. All infants received 23-valent pneumococcal polysaccharide vaccine (PPV at age 9 months. Serotype-specific serum IgG for PCV7 (VT serotypes and non-VT serotypes 2, 5 and 7F were measured at birth and 2, 3, 4, 9, 10 and 18 months of age. Primary outcomes were geometric mean concentrations (GMCs and proportions with concentration ≥ 0.35 µg/ml of VT serotype-specific pneumococcal IgG at age 2 months and one month post-PPV.We enrolled 101, 105 and 106 infants, respectively, into neonatal, infant and control groups. Despite high background levels of maternally derived antibody, both PCV7 groups had higher GMCs than controls at age 2 months for serotypes 4 (p<0.001 and 9V (p<0.05 and at age 3 months for all VTs except 6B. GMCs for serotypes 4, 9V, 18C and 19F were significantly higher (p<0.001 at age 2 months in the neonatal (one month post-dose2 PCV7 than in the infant group (one month post-dose1 PCV7. PPV induced significantly higher VT antibody responses in PCV7-primed than unprimed infants, with neonatal and infant groups equivalent. High VT and non-VT antibody concentrations generally persisted to age 18 months.PCV7 is well-tolerated and immunogenic in PNG neonates and young infants and induces immunologic memory to PPV booster at age 9 months with antibody levels maintained to age 18 months.ClinicalTrials.gov NCT00219401.
Many causes can be proposed for a change in the microbiologic makeup of a specific disease state. However, when viewed through the scope of recent events, only one is likely to be the true cause of a change in the microbiology of acute otitis media (AOM): the release and widespread use of heptavalent pneumococcal conjugate vaccine (PCV-7). The aim of this report was to review the microbiology and prevalence of AOM before and after the release and widespread use of PCV-7. For this brief review, we used a MEDLINE search to identify English-language literature related to the microbiology of AOM before and after the release of PCV-7 in 2000 in the United States (key terms: acute otitis media, AOM, Haemophilus influenzae, H influenzae, Streptococcus pneumoniae, and S pneumoniae; years: 1980-2005). Studies using tympanocentesis to identify the pathogen in recurrent or persistent AOM were examined; US studies reporting AOM microbiology before and after the release of PCV-7 in the same population were considered for the post-PCV-7 analysis. Following the release of PCV-7, a decrease in the overall rates of AOM was noted. This decrease brings into question the resultant effect on the microbiology of AOM. Our literature search revealed 2 studies that examined the microbiology of AOM before and after the release of PCV-7 in the United States. These 2 studies, conducted in dispersed geographic regions (rural Kentucky and Rochester, New York), illustrated a change in the predominant causative pathogen in AOM, from S pneumoniae to H influenzae in the population of children 7 to 24 months of age with recurrent AOM. Given the time period of the change, these shifts could be related to the release and widespread use of PCV-7. Since the 1990s, the predominant causative pathogen in recurrent AOM changed from S pneumoniae to H influenzae, possibly as a result of the release and widespread use of PCV 7. Although PCV-7 use was slowed from August 2001 to May 2003 and again from February
Immunogenicity and safety of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) co-administered with DTPa vaccine in Japanese children: A randomized, controlled study.
Iwata, Satoshi; Kawamura, Naohisa; Kuroki, Haruo; Tokoeda, Yasunobu; Miyazu, Mitsunobu; Iwai, Asayuki; Oishi, Tomohiro; Sato, Tomohide; Suyama, Akari; François, Nancy; Shafi, Fakrudeen; Ruiz-Guiñazú, Javier; Borys, Dorota
This phase III, randomized, open-label, multicenter study (NCT01027845) conducted in Japan assessed the immunogenicity, safety, and reactogenicity of 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV, given intramuscularly) co-administered with diphtheria-tetanus-acellular pertussis vaccine (DTPa, given subcutaneously). Infants (N=360 ) were randomized (2:1) to receive either PHiD-CV and DTPa (PHiD-CV group) or DTPa alone (control group) as 3-dose primary vaccination (3-4-5 months of age) and booster vaccination (17-19 months of age). Immune responses were measured before and one month after primary/booster vaccination and adverse events (AEs) were recorded. Post-primary immune responses were non-inferior to those in pivotal/efficacy European or Latin American pneumococcal protein D-conjugate vaccine studies. For each PHiD-CV serotype, at least 92.6% of infants post-primary vaccination and at least 97.7% of children post-booster had pneumococcal antibody concentrations ≥0.2 μg/ml, and at least 95.4% post-primary and at least 98.1% post-booster had opsonophagocytic activity (OPA) titers ≥8 . Geometric mean antibody concentrations and OPA titers (except OPA titer for 6B) were higher post-booster than post-priming for each serotype. All PHiD-CV-vaccinated children had anti-protein D antibody concentrations ≥100 EL.U/ml one month post-primary/booster vaccination and all were seroprotected/seropositive against each DTPa antigen. Redness and irritability were the most common solicited AEs in both groups. Incidences of unsolicited AEs were comparable between groups. Serious AEs were reported for 47 children (28 in PHiD-CV group); none were assessed as vaccine-related. In conclusion, PHiD-CV induced robust immune responses and was well tolerated when co-administered with DTPa in a 3-dose priming plus booster regimen to Japanese children.
Olivier Le Polain de Waroux
Full Text Available INTRODUCTION: Data on the prevalence of nasopharyngeal carriage of S.pneumoniae in all age groups are important to help predict the impact of introducing pneumococcal conjugate vaccines (PCV into routine infant immunization, given the important indirect effect of the vaccine. Yet most carriage studies are limited to children under five years of age. We here explore the association between carriage prevalence and serotype distribution in children aged ≥5 years and in adults compared to children. METHODS: We conducted a systematic review of studies providing carriage estimates across age groups in healthy populations not previously exposed to PCV, using MEDLINE and Embase. We used Bayesian linear meta-regression models to predict the overall carriage prevalence as well as the prevalence and distribution of vaccine and nonvaccine type (VT and NVT serotypes in older age groups as a function of that in <5 y olds. RESULTS: Twenty-nine studies compromising of 20,391 individuals were included in the analysis. In all studies nasopharyngeal carriage decreased with increasing age. We found a strong positive linear association between the carriage prevalence in pre-school childen (<5 y and both that in school aged children (5-17 y olds and in adults. The proportion of VT serotypes isolated from carriers was consistently lower in older age groups and on average about 73% that of children <5 y among 5-17 y olds and adults respectively. We provide a prediction model to infer the carriage prevalence and serotype distribution in 5-17 y olds and adults as a function of that in children <5 years of age. CONCLUSION: Such predictions are helpful for assessing the potential population-wide effects of vaccination programmes, e.g. via transmission models, and thus assist in the design of future pneumococcal conjugate vaccination strategies.
Le Polain de Waroux, Olivier; Flasche, Stefan; Prieto-Merino, David; Edmunds, W John
Data on the prevalence of nasopharyngeal carriage of S.pneumoniae in all age groups are important to help predict the impact of introducing pneumococcal conjugate vaccines (PCV) into routine infant immunization, given the important indirect effect of the vaccine. Yet most carriage studies are limited to children under five years of age. We here explore the association between carriage prevalence and serotype distribution in children aged ≥5 years and in adults compared to children. We conducted a systematic review of studies providing carriage estimates across age groups in healthy populations not previously exposed to PCV, using MEDLINE and Embase. We used Bayesian linear meta-regression models to predict the overall carriage prevalence as well as the prevalence and distribution of vaccine and nonvaccine type (VT and NVT) serotypes in older age groups as a function of that in linear association between the carriage prevalence in pre-school childen (<5 y) and both that in school aged children (5-17 y olds) and in adults. The proportion of VT serotypes isolated from carriers was consistently lower in older age groups and on average about 73% that of children <5 y among 5-17 y olds and adults respectively. We provide a prediction model to infer the carriage prevalence and serotype distribution in 5-17 y olds and adults as a function of that in children <5 years of age. Such predictions are helpful for assessing the potential population-wide effects of vaccination programmes, e.g. via transmission models, and thus assist in the design of future pneumococcal conjugate vaccination strategies.
Chan, C Y; Molrine, D C; Antin, J H; Wheeler, C; Guinan, E C; Weinstein, H J; Phillips, N R; McGarigle, C; Harvey, S; Schnipper, C; Ambrosino, D M
Accelerated granulocyte and platelet recovery following peripheral blood stem cell transplantation (PBSCT) are well documented. We hypothesize that functional immunity may also be enhanced in PBSCT and performed a phase II trial of immunizations in patients with lymphoma undergoing autologous transplantation with peripheral blood stem cells or bone marrow. Seventeen BMT and 10 PBSCT recipients were immunized at 3, 6, 12, and 24-months post-transplantation with Haemophilus influenzae type b (HIB)-conjugate and tetanus toxoid (TT) vaccines. IgG anti-HIB and anti-TT antibody concentrations were measured and compared between the two groups. Geometric mean IgG anti-HIB antibody concentrations were significantly higher for PBSCT recipients compared to BMT recipients at 24 months post-transplantation (11.3 micrograms/ml vs 0.93 microgram/ml, P = 0.051) and following the 24 month immunization (66.2 micrograms/ml vs 1.30 micrograms/ml, P = 0.006). Similar results were noted for IgG anti-TT antibody with significantly higher geometric mean antibody concentrations in the PBSCT group at 24 months post-transplantation (182 micrograms/ml vs 21.6 micrograms/ml, P = 0.039). Protective levels of total anti-HIB antibody were achieved earlier in PBSCT recipients compared with those of BMT recipients. PBSCT recipients had higher antigen-specific antibody concentrations following HIB and TT immunizations. These results suggest enhanced recovery of humoral immunity in PBSCT recipients and earlier protection against HIB with immunization.
Kedibone M Ndlangisa
Full Text Available We determined the sequence types of isolates that caused invasive pneumococcal disease (IPD prior to routine use of pneumococcal conjugate vaccines (PCV in South Africa. PCV-13 serotypes and 6C isolates collected in 2007 (1 461/2 437, 60% from patients of all ages as part of on-going, national, laboratory-based surveillance for IPD, were selected for genetic characterization. In addition, all 134 non-PCV isolates from children <2 years were selected for characterization. Sequence type diversity by serotype and age category (children <5 years vs. individuals ≥5 years was assessed for PCV serotypes using Simpson's index of diversity. Similar genotypes circulated among isolates from children and adults and the majority of serotypes were heterogeneous. While globally disseminated clones were common among some serotypes (e.g., serotype 1 [clonal complex (CC 217, 98% of all serotype 1] and 14 [CC230, 43%], some were represented mainly by clonal complexes rarely reported elsewhere (e.g., serotype 3 [CC458, 60%] and 19A [CC2062, 83%]. In children <2 years, serotype 15B and 8 were the most common serotypes among non-PCV isolates (16% [22/134] and 15% [20/134] isolates, respectively. Sequence type 7052 and 53 were most common among serotypes 15B and 8 isolates and accounted for 58% (7/12 and 64% (9/14 of the isolates, respectively. Serotype 19F, 14, 19A and 15B had the highest proportions of penicillin non-susceptible isolates. Genotypes rarely reported in other parts of the world but common among some of our serotypes highlight the importance of our data as these genotypes may emerge post PCV introduction.
A randomised trial to evaluate the immunogenicity, reactogenicity, and safety of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) co-administered with routine childhood vaccines in Singapore and Malaysia.
Lim, Fong Seng; Koh, Mia Tuang; Tan, Kah Kee; Chan, Poh Chong; Chong, Chia Yin; Shung Yehudi, Yeo Wee; Teoh, Yee Leong; Shafi, Fakrudeen; Hezareh, Marjan; Swinnen, Kristien; Borys, Dorota
The immunogenicity, reactogenicity, and safety of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) co-administered with routine childhood vaccines were evaluated among infants from Singapore and Malaysia, where PHiD-CV has been licensed. In the primary vaccination phase, 298 infants from Singapore and 168 infants from Malaysia were randomised to receive the Phase III Clinical (Clin) or the Commercial (Com) lot of PHiD-CV at 2, 3, and 5 months of age. In the booster vaccination phase, 238 toddlers from Singapore received one dose of the PHiD-CV Commercial lot at 18-21 months of age. Immune responses to pneumococcal polysaccharides were measured using 22F-inhibition enzyme-linked immunosorbent assay (ELISA) and functional opsonophagocytic activity (OPA) assay and to protein D, using ELISA. Immune responses induced by primary vaccination with the PHiD-CV Commercial lot were non-inferior to the Phase III Clinical lot in terms of adjusted antibody geometric mean concentration (GMC) ratios for each vaccine pneumococcal serotype and protein D. For each vaccine pneumococcal serotype, ≥93.6% and ≥88.5% of infants from Malaysia and Singapore had post-primary vaccination antibody concentrations ≥0.2 μg/mL and OPA titres ≥8, in the Clin and Com groups, respectively. For each vaccine pneumococcal serotype, ≥60.8% and ≥98.2% of toddlers from Singapore had pre- and post-booster antibody concentrations ≥0.2 μg/mL, in the Clin and Com groups, respectively. All children, except one, had measurable anti-protein D antibodies and the primary and booster doses of the co-administered vaccines were immunogenic. The incidence of each grade 3 solicited symptom was ≤11.1% in both study phases. No serious adverse events considered causally related to vaccination were reported throughout the study. PHiD-CV given as three-dose primary vaccination to infants in Singapore and Malaysia and booster vaccination to toddlers in
The immunogenicity and safety of a tetravalent measles-mumps-rubella-varicella vaccine when co-administered with conjugated meningococcal C vaccine to healthy children: A phase IIIb, randomized, multi-center study in Italy.
Durando, Paolo; Esposito, Susanna; Bona, Gianni; Cuccia, Mario; Desole, Maria Giuseppina; Ferrera, Giuseppe; Gabutti, Giovanni; Pellegrino, Angelo; Salvini, Filippo; Henry, Ouzama; Povey, Michael; Marchetti, Federico
Multiple vaccination visits and administrations can be stressful for infants, parents and healthcare providers. Multivalent combination vaccines can deliver the required number of antigens in fewer injections and clinic visits, while vaccine co-administration can also reduce the number of visits. This non-inferiority study was undertaken to evaluate the feasibility of co-administering a combined measles-mumps-rubella-varicella (MMRV) vaccine with conjugated meningococcal C (MenC) vaccine in a large cohort of healthy Italian toddlers. Healthy subjects aged 13-15months were randomized (2:1:1) to receive single doses of either: co-administered MMRV+MenC at the same visit (MMRV+MenC group); or MMRV followed 42days later by MenC (MMRV group); or MenC followed 42days later by MMRV (MenC group). Blood samples were collected before and 43days after vaccination. Antibody titers against MMRV were measured using ELISA. Functional-anti-meningococcal-serogroup activity (rSBAMenC) was assessed using a serum bactericidal test. Solicited local and general reactions were recorded for up to 4 and 42days post-vaccination, respectively. Non-inferiority of MMRV+MenC to MMRV (post-dose-1 seroconversion rates) and MMRV+MenC to MenC (post-dose-1 seroprotection rates) was achieved if the lower limit (LL) of the 95% confidence interval (CI) for the group difference was ⩾-10% for each antigen. 716 subjects were enrolled in the study. At 42days post-vaccination, the MMRV seroconversion rates were 99.3% (measles), 94.5% (mumps), 100% (rubella) and 99.7% (varicella) in the MMRV+MenC group, and 99.4%, 93.2%, 100% and 100%, respectively, in the MMRV group. The seroprotection rates against rSBA-MenC were 98.3% in the MMRV+MenC group and 99.3% in the MenC group. Non-inferiority was reached for all the vaccine antigens. The safety profiles were as expected for these vaccines. The immune responses elicited by co-administered MMRV+MenC were non-inferior to those elicited by MMRV or MenC alone and
Daugla, D M; Gami, J P; Gamougam, K; Naibei, N; Mbainadji, L; Narbé, M; Toralta, J; Kodbesse, B; Ngadoua, C; Coldiron, M E; Fermon, F; Page, A-L; Djingarey, M H; Hugonnet, S; Harrison, O B; Rebbetts, L S; Tekletsion, Y; Watkins, E R; Hill, D; Caugant, D A; Chandramohan, D; Hassan-King, M; Manigart, O; Nascimento, M; Woukeu, A; Trotter, C; Stuart, J M; Maiden, McJ; Greenwood, B M
A serogroup A meningococcal polysaccharide-tetanus toxoid conjugate vaccine (PsA-TT, MenAfriVac) was licensed in India in 2009, and pre-qualified by WHO in 2010, on the basis of its safety and immunogenicity. This vaccine is now being deployed across the African meningitis belt. We studied the effect of PsA-TT on meningococcal meningitis and carriage in Chad during a serogroup A meningococcal meningitis epidemic. We obtained data for the incidence of meningitis before and after vaccination from national records between January, 2009, and June, 2012. In 2012, surveillance was enhanced in regions where vaccination with PsA-TT had been undertaken in 2011, and in one district where a reactive vaccination campaign in response to an outbreak of meningitis was undertaken. Meningococcal carriage was studied in an age-stratified sample of residents aged 1-29 years of a rural area roughly 13-15 and 2-4 months before and 4-6 months after vaccination. Meningococci obtained from cerebrospinal fluid or oropharyngeal swabs were characterised by conventional microbiological and molecular methods. Roughly 1·8 million individuals aged 1-29 years received one dose of PsA-TT during a vaccination campaign in three regions of Chad in and around the capital N'Djamena during 10 days in December, 2011. The incidence of meningitis during the 2012 meningitis season in these three regions was 2·48 per 100,000 (57 cases in the 2·3 million population), whereas in regions without mass vaccination, incidence was 43·8 per 100,000 (3809 cases per 8·7 million population), a 94% difference in crude incidence (pvaccinated regions. 32 serogroup A carriers were identified in 4278 age-stratified individuals (0·75%) living in a rural area near the capital 2-4 months before vaccination, whereas only one serogroup A meningococcus was isolated in 5001 people living in the same community 4-6 months after vaccination (adjusted odds ratio 0·019, 95% CI 0·002-0·138; p<0·0001). PSA-TT was highly
Kristensen, K; Barington, T; Pressler, T
single total IgG subclass, but total IgG measured as the sum of all four subclasses was significantly lower in the children with RLRI than in the controls (P = 0.036). Before vaccination, the children with RLRI had significantly less IgG antipolysaccharide Hib antibody than the controls (P = 0......M response to Hib conjugate vaccine in these children, since this isotype predominates in the primary immune response, i.e., in the absence of immunologic memory.(ABSTRACT TRUNCATED AT 250 WORDS)......Children with recurrent lower respiratory tract infection (RLRI) may respond poorly to polysaccharide antigens. To examine how such children respond to a polysaccharide coupled to a protein carrier, we immunized 15 children with RLRI aged 8-69 months and 15 carefully age-matched healthy controls...
Is 13-Valent Pneumococcal Conjugate Vaccine (PCV13 Combined With 23-Valent Pneumococcal Polysaccharide Vaccine (PPSV23 Superior to PPSV23 Alone for Reducing Incidence or Severity of Pneumonia in Older Adults? A Clin-IQ
Full Text Available Pneumonia infection is a significant cause of morbidity and mortality worldwide. In addition to the public health concerns, pneumonia also accounts for a significant cost to the health care system. Currently there are two leading vaccines targeted against Streptococcus pneumoniae: 23-valent pneumococcal polysaccharide vaccine (PPSV23 and 13-valent pneumococcal conjugate vaccine (PCV13. Until recently, the recommendation for adult pneumonia vaccination has been a single dose of PPSV23 for all adults aged 65 years or older. However, concerns were raised regarding the vaccine’s efficacy due to the persistent burden of pneumococcal disease in the elderly population. This paper focuses on two trials that evaluated the safety and efficacy of PCV13 in the adult population. The first study reveals improved immune response with the addition of PCV13 to PPSV23, while the second shows PCV13 was effective in the prevention of vaccine-type community-acquired pneumonia. Both studies observed adequate safety profiles for PCV13 in series with PPSV23 and with PCV13 compared to placebo.
Silva, Giselle P; Santos, Rafaela S; Pereira-Manfro, Wânia F; Ferreira, Bianca; Barreto, Daniella M; Frota, Ana Cristina C; Hofer, Cristina B; Milagres, Lucimar G
Anti-diphtheria antibody levels decrease with aging, and frequent booster vaccinations are required to maintain herd immunity. We analyzed the diphtheria toxin neutralizing antibody (DT-Nab) response induced by a conjugate vaccine (meningococcal C polysaccharide-CRM 197 ) in HIV-vertically infected (HI) children and adolescents and healthy controls (HC) with matched age. We report the association of DT-Nab with the bactericidal antibodies to serogroup C meningococcus (MenC). Before vaccination, 21 HI patients (50%) had no protection against diphtheria (≤0.01IU/ml of antibody) and only 8 (19%) showed complete protection (≥0.1IU/ml). About half of the HC (56%) had complete protection before immunization and 6 subjects (12%) had no protection against diphtheria. After one and two vaccine injections, 96% of HC and 64% of HI vaccinees, respectively, showed full protection against diphtheria. These data indicate that CRM 197 was able to induce primary and/or booster response in both groups of individuals. Copyright © 2017 Elsevier Ltd. All rights reserved.
dos Santos, Silvia R; Passadore, Lilian F; Takagi, Elizabeth H; Fujii, Cristiane M; Yoshioka, Cristina R M; Gilio, Alfredo E; Martinez, Marina B
The ten-pneumococcal conjugate vaccine (PCV10) was introduced into the national immunization program for childhood vaccination schedules by the Brazilian Health Public Service in March 2010. The aim of this study was to compare Streptococcus pneumoniae serotype distribution, antibiotic resistance patterns, and potential coverage before (January 2006-June 2010) and after (July 2010-September 2012) PCV10 introduction. The incidence of invasive pneumococcal disease (IPD), patient demographics, and disease characteristics were recorded. This study was conducted at the University Hospital of Sao Paulo University in Brazil from January 2006 to September 2012. Serotyping was performed using multiplex PCR typing, and antimicrobial sensitivity by Clinical and Laboratory Standards Institute (CLSI). A total of 259 S. pneumoniae strains were isolated from patients with IPD. The ages of the patients ranged from 3 months to 95 years old. The strains were isolated from cerebrospinal fluid, pleural fluid, and blood. The incidence of IPD among patients at HU-USP changed after the introduction of PCV10. The overall incidence of IPD was 3.42 cases per 1000 admissions in the vaccine pre- implementation period and of 2.99 cases per 1000 admissions in the vaccine post-implementation period. The incidence of IPD among children<2 y.o. attended at HU-USP changed significantly after the introduction of PCV10, from 20.30 to 3.97 of incidence. The incidence of PCV10- serotypes decrease from 16.47 to 0.44 in the same age, before and after PC10 implementation, respectively. Moreover, it was possible to realize the sensitivity to penicillin among isolates increased significantly in the post-vaccine period. Data from this study suggest that PCV10 contributed to decrease with PID rate among children less than 2 y.o. The resistance rate among pneumococcal isolates also could be observed since serotypes with greater resistance to beta lactam antibiotics were not easily isolated after vaccination
Manuel Alexander Haasis
Full Text Available The objective of this study is to assess the value for money of introducing pneumococcal conjugate vaccines as part of the immunization program in a lower-middle income country, the Philippines, which is not eligible for GAVI support and lower vaccine prices. It also includes the newest clinical evidence evaluating the efficacy of PCV10, which is lacking in other previous studies.A cost-utility analysis was conducted. A Markov simulation model was constructed to examine the costs and consequences of PCV10 and PCV13 against the current scenario of no PCV vaccination for a lifetime horizon. A health system perspective was employed to explore different funding schemes, which include universal or partial vaccination coverage subsidized by the government. Results were presented as incremental cost-effectiveness ratios (ICERs in Philippine peso (Php per QALY gained (1 USD = 44.20 Php. Probabilistic sensitivity analysis was performed to determine the impact of parameter uncertainty.With universal vaccination at a cost per dose of Php 624 for PCV10 and Php 700 for PCV13, both PCVs are cost-effective compared to no vaccination given the ceiling threshold of Php 120,000 per QALY gained, yielding ICERs of Php 68,182 and Php 54,510 for PCV10 and PCV13, respectively. Partial vaccination of 25% of the birth cohort resulted in significantly higher ICER values (Php 112,640 for PCV10 and Php 84,654 for PCV13 due to loss of herd protection. The budget impact analysis reveals that universal vaccination would cost Php 3.87 billion to 4.34 billion per annual, or 1.6 to 1.8 times the budget of the current national vaccination program.The inclusion of PCV in the national immunization program is recommended. PCV13 achieved better value for money compared to PCV10. However, the affordability and sustainability of PCV implementation over the long-term should be considered by decision makers.
Thompson, Allison; Gurtman, Alejandra; Patterson, Scott; Juergens, Christine; Laudat, France; Emini, Emilio A; Gruber, William C; Scott, Daniel A
Meta-analyses enable summarization and interpretation of data across clinical trials. When applied to safety data they allow for detection of rare events. Recently, a 13-valent pneumococcal conjugate vaccine (PCV13) was approved in multiple countries worldwide for routine immunization of infants and young children. This meta-analysis was conducted to identify potentially clinically important rare safety events associated with PCV13. To summarize the safety of PCV13 compared with 7-valent pneumococcal conjugate vaccine (PCV7) administered to infants and toddlers. A meta-analysis was performed of integrated safety data from 13 infant studies (PCV13 n=4729 and PCV7 n=2760) conducted in 9 North American, European, and Asian countries. Local reactions at the vaccine injection site and systemic events were collected for 4-7 days after each dose into electronic diaries. Adverse events (AEs) were collected after each vaccination. Overall, rates of local reactions after any dose of the infant series were similar between PCV13 and PCV7 groups: tenderness (46.7% vs 44.8%, respectively); swelling (28.5% vs 26.9%); and redness (36.4% vs 33.9%). After the toddler dose, tenderness was significantly higher among PCV7 subjects than PCV13 subjects (54.4% vs 48.8%; P=0.005). Frequencies of fever (≥38°C) were similar in both groups and mostly mild (≤39°C); incidence of moderate fever (>39°C to ≤40°C) with PCV13 was ≤2.8% after any infant dose and 5.0% after the toddler dose, compared with ≤2.6% and 7.3%, respectively, with PCV7. Fever >40°C was uncommon in both groups. Frequencies of decreased appetite, irritability, and sleep disturbances were similar in both groups. AEs were the types of conditions and symptoms expected in infants and children, and clinically significant differences between vaccine groups were not observed. PCV13 has a favorable safety profile similar to that of PCV7, a vaccine for which there is >10 years clinical experience. Copyright © 2013
Abu-baker, N. F.; Masoud, H. A.; Jaber, B. M.
Pseudomonas aeruginosa is an improtant opportunistic pathogen that can cause infection in immunocompromised patient. Lipopolysaccharide (LPS), the major surface antigen of P. aeruginosa, is immunogenic and elieits protective antibodies in animals. The O-polysaccharids (O-PS) from international Antigenic typing Scheme (IATS) 10, the antigenic determinant of LPS, was coupled to recombinant exoprotein A (rPA) through adipic acid dihydrazide (ADH) mediated by carbodiimide condensation reaction. Mice were immunized with the conjugate emulsifield with monophosphoryl lipid A-trehalose dicorynomycolate (MPL-T) and freund's adjuvants. The conjiugate emulsified with MPL-T adjuvant elicited the highest level of IgG and IgM followed by freuns's adjuvant. IgG titers using both MPL-T and freund's adjuvants were recorded to be higher than IgM titers after the second post of the immunization. Immunization of mice with the prepared conjugates emulsified with MPL-T and freund's adjvaided provide high level of protection (100%) against ten times the LD50 of homologous strain of P. aeruginsoa. the elicited high IgG level and the in vivo protection test results provided good evidences for the possible protection of the conjugate aginst subsequent infection with the pathogen. These findings will enable us to use it as protective vaccine candidate (authors).
Kelly, Dominic F; Snape, Matthew D; Perrett, Kirsten P; Clutterbuck, Elizabeth A; Lewis, Susan; Blanchard Rohner, Geraldine; Jones, Meryl; Yu, Ly-Mee; Pollard, Andrew J
The induction of persistent protective levels of pathogen-specific antibody is an important goal of immunization against childhood infections. However, antibody persistence is poor after immunization in infancy versus later in life. Serogroup C meningococci (MenC) are an important cause of bacteraemia and meningitis in children. The use of protein-polysaccharide conjugate vaccines against MenC has been associated with a significant decline in the incidence of invasive disease. However, vaccine effectiveness is negligible by more than 1 year after a three-dose priming series in infancy and corresponds to a rapid decline in antibody following an initial immune response. The cellular mechanisms underlying the generation of persistent antibody in this age group are unclear. An essential prelude to larger studies of peripheral blood B cells is an understanding of B-cell kinetics following immunization. We measured MenC- and diphtheria-specific plasma and memory B-cell kinetics in infants receiving a CRM(197) (cross-reactive material; mutant diphtheria toxoid)-conjugated MenC vaccine at 2, 3 and 4 months of age. Plasma cell responses were more delayed after the first dose when compared with the rapid appearance of plasma cells after the third dose. Memory B cells were detectable at all time-points following the third dose as opposed to the low frequency seen following a first dose. This study provides data on B-cell kinetics following a primary schedule of immunization in young infants upon which to base further studies of the underlying cellular mechanism of humoral immunity.
Becker-Dreps, Sylvia; Blette, Bryan; Briceño, Rafaela; Alemán, Jorge; Hudgens, Michael G; Moreno, Gilberto; Ordoñez, Ana; Rocha, Julio; Weber, David J; Amaya, Erick
Streptococcus pneumoniae causes about 826,000 deaths of children in the world each year and many health facility visits. To reduce the burden of pneumococcal disease, many nations have added pneumococcal conjugate vaccines to their national immunization schedules. Nicaragua was the first country eligible for GAVI Alliance funding to introduce the 13-valent pneumococcal conjugate vaccine (PCV13) in 2010, provided to infants at 2, 4, and 6 months of age. The goal of this study was to evaluate the population impact of the first five years of the program. Numbers of visits for pneumonia, pneumonia-related deaths, and bacterial meningitis in both children and adults, and infant deaths between 2008 and 2015 were collected from all 107 public health facilities in León Department. Vital statistics data provided additional counts of pneumonia-related deaths that occurred outside health facilities. Adjusted incidence rates and incidence rate ratios (IRRa) in the vaccine (2011-2015) and pre-vaccine periods (2008-2010) were estimated retrospectively using official population estimates as exposure time. The IRRa for pneumonia hospitalizations was 0.70 (95% confidence interval [CI]: 0.66, 0.75) for infants, and 0.92 (95% CI: 0.85, 0.99) for one year-olds. The IRRa for post-neonatal infant mortality was 0.56 (95% CI: 0.41, 0.77). In the population as a whole, ambulatory visits and hospitalizations for pneumonia, as well as pneumonia-related mortality and rates of bacterial meningitis were lower in the vaccine period. During the first five years of program implementation, reductions were observed in health facility visits for pneumonia in immunized age groups and infant mortality, which would be hard to achieve with any other single public health intervention. Future study is warranted to understand whether the lack of a booster dose (e.g., at 12 months) may be responsible for the small reductions in pneumonia hospitalizations observed in one year-olds as compared to infants.
Immunogenicity and safety of a fully liquid aluminum phosphate adjuvanted Haemophilus influenzae type b PRP-CRM197-conjugate vaccine in healthy Japanese children: A phase III, randomized, observer-blind, multicenter, parallel-group study.
Togashi, Takehiro; Mitsuya, Nodoka; Kogawara, Osamu; Sumino, Shuji; Takanami, Yohei; Sugizaki, Kayoko
Broad use of monovalent Haemophilus influenzae type b (Hib) conjugate vaccines based on the capsular polysaccharide polyribosyl-ribitol phosphate (PRP), has significantly reduced invasive Hib disease burden in children worldwide, particularly in children aged vaccine has been widely used since the initiation of public funding programs followed by a routine vaccination designation in 2013. We compared the immunogenicity and safety of PRP conjugated to a non-toxic diphtheria toxin mutant (PRP-CRM197) vaccine with the PRP-T vaccine when administered subcutaneously to healthy Japanese children in a phase III study. Additionally, we evaluated the immunogenicity and safety profiles of a diphtheria-tetanus acellular pertussis (DTaP) combination vaccine when concomitantly administered with either PRP-CRM197 or PRP-T vaccines. The primary endpoint was the "long-term seroprotection rate", defined as the group proportion with anti-PRP antibody titers ⩾1.0μg/mL, after the primary series. Long-term seroprotection rates were 99.3% in the PRP-CRM197 group and 95.6% in the PRP-T group. The intergroup difference (PRP-CRM197 group - PRP-T group) was 3.7% (95% confidence interval: 0.099-7.336), demonstrating that PRP-CRM197 vaccine was non-inferior to PRP-T vaccine (pvaccination was higher in the PRP-CRM197 group than in PRP-T. Concomitant administration of PRP-CRM197 vaccine with DTaP vaccine showed no differences in terms of immunogenicity compared with concomitant vaccination with PRP-T vaccine and DTaP vaccine. Although CRM197 vaccine had higher local reactogenicity, overall, both Hib vaccines had acceptable safety and tolerability profiles. The immunogenicity of PRP-CRM197 vaccine administered subcutaneously as a three-dose primary series in children followed by a booster vaccination 1year after the primary series induced protective levels of Hib antibodies with no safety or tolerability concerns. Registered on ClinicalTrials.gov: NCT01379846. Copyright © 2016 The Authors
Nagel, J.; Saxne, T.; Geborek, P.
in addition to standard of care therapy or with only hydroxychloroquine did not differ compared to controls, whereas the other treatment groups had significantly lower fold increase of post-vaccination antibody levels. Higher age was associated with lower post-vaccination antibody levels among systemic lupus...
Navne, Johan Emdal; Koch, Anders; Slotved, Hans-Christian
. Overall carriage rate of S. pneumoniae remained unchanged from 2011 to 2013 (51% and 56%, p=0.13), but significant serotype shifts were observed among both vaccinated and unvaccinated children with marked reductions in carriage of vaccine-type pneumococci, counterbalanced by increasing carriage of non...
Winther, Thilde N; Kristensen, Tim D; Kaltoft, Margit S
Aim: The aim of this study was to document the epidemiology, microbiology and outcome of invasive pneumococcal disease (IPD) among children vaccine (PCV7) into the Danish routine...... children vaccination....... immunization programme October 2007. Methods: Clinical and microbiological records on cases of IPD in children children
Fiorino, Fabio; Ciabattini, Annalisa; Rondini, Simona; Pozzi, Gianni; Martin, Laura B; Medaglini, Donata
Typhoid fever is a public health problem, especially among young children in developing countries. To address this need, a glycoconjugate vaccine Vi-CRM₁₉₇, composed of the polysaccharide antigen Vi covalently conjugated to the non-toxic mutant of diphtheria toxin CRM₁₉₇, is under development. Here, we assessed the antibody and cellular responses, both local and systemic, following subcutaneous injection of Vi-CRM₁₉₇. The glycoconjugate elicited Vi-specific serum IgG titers significantly higher than unconjugated Vi, with prevalence of IgG1 that persisted for at least 60 days after immunization. Vi-specific IgG, but not IgA, were present in intestinal washes. Lymphocytes proliferation after restimulation with Vi-CRM₁₉₇ was observed in spleen and mesenteric lymph nodes. These data confirm the immunogenicity of Vi-CRM₁₉₇ and demonstrate that the vaccine-specific antibody and cellular immune responses are present also in the intestinal tract, thus strengthening the suitability of Vi-CRM₁₉₇ as a promising candidate vaccine against Salmonella Typhi. Copyright © 2012 Elsevier Ltd. All rights reserved.
Wysocki, Jacek; Brzostek, Jerzy; Szymański, Henryk; Tetiurka, Bogusław; Toporowska-Kowalska, Ewa; Wasowska-Królikowska, Krystyna; Sarkozy, Denise A; Giardina, Peter C; Gruber, William C; Emini, Emilio A; Scott, Daniel A
Streptococcus pneumoniae infections are a major cause of morbidity and mortality in children vaccine (PCV13) has been developed and approved in many countries worldwide. Assess the safety and immunogenicity of PCV13 in healthy older infants and children naïve to previous pneumococcal vaccination. This was a phase 3, open-label, multicenter study conducted in Polish children (N=354) who were vaccinated according to 3 age-appropriate catch-up schedules: Group 1 (aged 7 to vaccine doses only; and Group 3 (aged 24 to vaccine, was determined for each vaccine serotype. In addition, antipolysaccharide immunoglobulin (Ig) G geometric mean concentrations (GMCs) were calculated. Safety assessments included systemic and local reactions, and adverse events. The proportion of immunological responders was ≥88% across groups for all serotypes. Antipolysaccharide IgG GMCs were generally similar across groups. Each schedule elicited immune response levels against all 13 serotypes comparable to or greater than levels previously reported in infants after a 3-dose series. The 3 catch-up schedules had similar tolerability and safety profiles; a trend was present towards greater local tenderness with increasing age and subsequent dose administration. Immunological responses and safety results support the use of PCV13 for catch-up schedules in older infants and children naïve to pneumococcal vaccination. Copyright © 2015. Published by Elsevier Ltd.
Irma Gabriela Echániz-Avilés
Full Text Available Streptococcus pneumoniae is one of the leading causes of both invasive and noninvasive diseases in the pediatric population and continues to represent a significant public health burden worldwide. The increasing incidence of antibioticresistant strains of the pathogen has complicated treatment and management of the various pneumococcal disease manifestations. Thus, the best management strategy may be the prevention of pneumococcal diseases through vaccination. Although several pneumococcal conjugate vaccines have been clinically studied in infants and children, only a 7-valent conjugate vaccine (PNCRM7; Prevnar®/Prevenar® is currently approved for the prevention of invasive disease. Vaccination with PNCRM7 is safe and effective in infants and young children. Routine vaccination with the conjugate vaccine could improve outcomes by safeguarding against the development of antibiotic-resistant strains of S. pneumoniae, thus simplifying the management of pneumococcal disease. Additionally, the overall costs associated with the treatment of pneumococcal diseases could be substantially reduced, particularly in developing countries. The time has come for fully applying this new advancement against S. pneumoniae, to benefit the children of the world. The Spanish version of this paper is available at: http://www.insp.mx/salud/index.htmlStreptococcus pneumoniae es uno de los principales agentes causantes de enfermedades invasoras y no invasoras en la población pediátrica y sigue representando uno de los principales problemas de salud pública a nivel mundial. La incidencia creciente de cepas resistentes a diversos antimicrobianos ha complicado el tratamiento y manejo de varias de las manifestaciones de la enfermedad neumocócica. Con éstas consideraciones, la mejor estrategia de manejo es la prevención de éstas enfermedades a través de la vacunación. A pesar de que se han estudiado diversas vacunas neumocócicas conjugadas en niños, solo una
Marco Aurélio Palazzi Sáfadi
quadrivalente meningocócica conjugada representa, enfim, a real possibilidade de uma proteção mais abrangente contra a doença meningocócica, restando ainda a necessidade de se desenvolver uma vacina eficaz contra o meningococo B.OBJECTIVE: Meningococcal disease continues to be a serious public health concern, being associated with high morbidity and mortality rates worldwide, particularly in Brazil. In addition to discussing recent changes in the global epidemiology of meningococcal disease, we also analyze the development and impact of new conjugate vaccines on the prevention of meningococcal disease, with emphasis on the different immunization strategies implemented with these vaccines. SOURCES OF DATA: MEDLINE databases were searched from 1996 to 2006, with emphasis on review articles, clinical trials and epidemiological studies. Information was also sought on the Centers for Disease Control and Prevention, Brazilian Ministry of Health and Centro de Vigilância Epidemiológica do Estado de São Paulo websites. SUMMARY OF THE FINDINGS: Five serogroups (A, B, C, W135 and Y are responsible for virtually all cases of the disease worldwide, with marked regional and temporal differences. The new meningococcal serogroup C conjugate vaccines (MCC offer unmistakable advantages over polysaccharide vaccines. MCC vaccines generate a more efficient and long-lasting antibody response, inducing immunologic memory and reduction of nasopharyngeal carriage. The immediate results of introducing these vaccines into immunization programs have been encouraging, with a dramatic reduction in the incidence of serogroup C disease, not only in vaccinated, but also in unvaccinated individuals (herd immunity. However, concerns have arisen regarding the long-term effectiveness of these vaccines, especially for infants vaccinated in the routine schedule. CONCLUSIONS: The reported waning of efficacy more than 1 year after routine infant immunization supports alternative schedules incorporating a
... Vaccine Information Materials for Rotavirus Vaccine AGENCY: Centers for Disease Control and Prevention... information materials for rotavirus vaccine. DATES: Written comments are invited and must be received on or... (chickenpox), pneumococcal conjugate, rotavirus, hepatitis A, meningococcal, human papillomavirus (HPV), and...
Full Text Available Abstract Background New pre-clinical trials in AD mouse models may help to develop novel immunogen-adjuvant configurations with the potential to avoid the adverse responses that occurred during the clinical trials with AN-1792 vaccine formulation. Recently, we have pursued an alternative immunization strategy that replaces QS21 the Th1 type adjuvant used in the AN-1792 clinical trial with a molecular adjuvant, mannan that can promote a Th2-polarized immune response through interactions with mannose-binding and CD35/CD21 receptors of the innate immune system. Previously we established that immunization of wild-type mice with mannan-Aβ28 conjugate promoted Th2-mediated humoral and cellular immune responses. In the current study, we tested the efficacy of this vaccine configuration in amyloid precursor protein (APP transgenic mice (Tg2576. Methods Mannan was purified, activated and chemically conjugated to Aβ28 peptide. Humoral immune responses induced by the immunization of mice with mannan-Aβ28 conjugate were analyzed using a standard ELISA. Aβ42 and Aβ40 amyloid burden, cerebral amyloid angiopathy (CAA, astrocytosis, and microgliosis in the brain of immunized and control mice were detected using immunohistochemistry. Additionally, cored plaques and cerebral vascular microhemorrhages in the brains of vaccinated mice were detected by standard histochemistry. Results Immunizations with low doses of mannan-Aβ28 induced potent and long-lasting anti-Aβ humoral responses in Tg2576 mice. Even 11 months after the last injection, the immunized mice were still producing low levels of anti-Aβ antibodies, predominantly of the IgG1 isotype, indicative of a Th2 immune response. Vaccination with mannan-Aβ28 prevented Aβ plaque deposition, but unexpectedly increased the level of microhemorrhages in the brains of aged immunized mice compared to two groups of control animals of the same age either injected with molecular adjuvant fused with an irrelevant
Lehmann, Deborah; Kirarock, Wendy; van den Biggelaar, Anita H J; Passey, Megan; Jacoby, Peter; Saleu, Gerard; Masiria, Geraldine; Nivio, Birunu; Greenhill, Andrew; Orami, Tilda; Francis, Jacinta; Ford, Rebecca; Kirkham, Lea-Ann; Solomon, Vela; Richmond, Peter C; Pomat, William S
Children in third-world settings including Papua New Guinea (PNG) experience early onset of carriage with a broad range of pneumococcal serotypes, resulting in a high incidence of severe pneumococcal disease and deaths in the first 2 years of life. Vaccination trials in high endemicity settings are needed to provide evidence and guidance on optimal strategies to protect children in these settings against pneumococcal infections. This report describes the rationale, objectives, methods, study population, follow-up and specimen collection for a vaccination trial conducted in an endemic and logistically challenging setting in PNG. The trial aimed to determine whether currently available pneumococcal conjugate vaccines (PCV) are suitable for use under PNG's accelerated immunization schedule, and that a schedule including pneumococcal polysaccharide vaccine (PPV) in later infancy is safe and immunogenic in this high-risk population. This open randomized-controlled trial was conducted between November 2011 and March 2016, enrolling 262 children aged 1 month between November 2011 and April 2014. The participants were randomly allocated (1:1) to receive 10-valent PCV (10vPCV) or 13-valent PCV (13vPCV) in a 1-2-3-month schedule, with further randomization to receive PPV or no PPV at age 9 months, followed by a 1/5 th PPV challenge at age 23 months. A total of 1229 blood samples were collected to measure humoral and cellular immune responses and 1238 nasopharyngeal swabs to assess upper respiratory tract colonization and carriage load. Serious adverse events were monitored throughout the study. Of the 262 children enrolled, 87% received 3 doses of PCV, 79% were randomized to receive PPV or no PPV at age 9 months, and 67% completed the study at 24 months of age with appropriate immunization and challenge. Laboratory testing of the many samples collected during this trial will determine the impact of the different vaccine schedules and formulations on nasopharyngeal
Miguel W Tregnaghi
Full Text Available The relationship between pneumococcal conjugate vaccine-induced antibody responses and protection against community-acquired pneumonia (CAP and acute otitis media (AOM is unclear. This study assessed the impact of the ten-valent pneumococcal nontypable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV on these end points. The primary objective was to demonstrate vaccine efficacy (VE in a per-protocol analysis against likely bacterial CAP (B-CAP: radiologically confirmed CAP with alveolar consolidation/pleural effusion on chest X-ray, or non-alveolar infiltrates and C-reactive protein ≥ 40 µg/ml; other protocol-specified outcomes were also assessed.This phase III double-blind randomized controlled study was conducted between 28 June 2007 and 28 July 2011 in Argentine, Panamanian, and Colombian populations with good access to health care. Approximately 24,000 infants received PHiD-CV or hepatitis control vaccine (hepatitis B for primary vaccination, hepatitis A at booster at 2, 4, 6, and 15-18 mo of age. Interim analysis of the primary end point was planned when 535 first B-CAP episodes, occurring ≥2 wk after dose 3, were identified in the per-protocol cohort. After a mean follow-up of 23 mo (PHiD-CV, n = 10,295; control, n = 10,201, per-protocol VE was 22.0% (95% CI: 7.7, 34.2; one-sided p = 0.002 against B-CAP (conclusive for primary objective and 25.7% (95% CI: 8.4%, 39.6% against World Health Organization-defined consolidated CAP. Intent-to-treat VE was 18.2% (95% CI: 5.5%, 29.1% against B-CAP and 23.4% (95% CI: 8.8%, 35.7% against consolidated CAP. End-of-study per-protocol analyses were performed after a mean follow-up of 28-30 mo for CAP and invasive pneumococcal disease (IPD (PHiD-CV, n = 10,211; control, n = 10,140 and AOM (n = 3,010 and 2,979, respectively. Per-protocol VE was 16.1% (95% CI: -1.1%, 30.4%; one-sided p = 0.032 against clinically confirmed AOM, 67.1% (95% CI: 17.0%, 86.9% against vaccine serotype clinically
Myers, Tanya R; McNeil, Michael M; Ng, Carmen S; Li, Rongxia; Lewis, Paige W; Cano, Maria V
Limited data are available describing the post-licensure safety of meningococcal vaccines, including Menveo®. We reviewed reports of adverse events (AEs) to the Vaccine Adverse Event Reporting System (VAERS) to assess safety in all age groups. VAERS is a national spontaneous vaccine safety surveillance system co-administered by the Centers for Disease Control and Prevention and the US Food and Drug Administration. We searched the VAERS database for US reports of adverse events in persons who received Menveo from 1 January 2010 through 31 December 2015. We clinically reviewed reports and available medical records for serious AEs, selected pre-specified outcomes, and vaccination during pregnancy. We used empirical Bayesian data mining to identify AEs that were disproportionately reported after receipt of Menveo. During the study period, VAERS received 2614 US reports after receipt of Menveo. Of these, 67 were classified as serious, including 1 report of death. Adolescents (aged 11-18years) accounted for 74% of reports. Most of the reported AEs were non-serious and described AEs consistent with data from pre-licensure studies. Anaphylaxis and syncope were the two most common events in the serious reports. We did not identify any new safety concerns after review of AEs that exceeded the data mining threshold, although we did observe disproportionate reporting for terms that were not associated with an adverse event (e.g., "incorrect drug dosage form administered", "wrong technique in drug usage process"). Although reports were limited, we did not find any evidence for concern regarding the use of Menveo during pregnancy. In our review of VAERS reports, findings of AEs were consistent with the data from pre-licensure studies. Vaccine providers should continue to emphasize and adhere to proper administration of the vaccine. Copyright © 2017 Elsevier Ltd. All rights reserved.
Full Text Available BACKGROUND: Combining meningococcal vaccination with routine immunization in infancy may reduce the burden of meningococcal meningitis, especially in the meningitis belt of Africa. We have evaluated the immunogenicity, persistence of immune response, immune memory and safety of an investigational DTPw-HBV/Hib-MenAC conjugate vaccine given to infants in Northern Ghana. METHODS AND FINDINGS: In this phase II, double blind, randomized, controlled study, 280 infants were primed with DTPw-HBV/Hib-MenAC or DTPw-HBV/Hib vaccines at 6, 10 and 14 weeks of age. At 12 months of age, children in each group received a challenge dose of serogroup A+C polysaccharides. Antibody responses were assessed pre, and one month-post dose 3 of the priming schedule and pre and 1 month after administration of the challenge dose. One month post-dose 3, 87.8% and 88.2% of subjects in the study group had bactericidal meningococcal serogroup A (SBA-MenA and meningococcal serogroup C (SBA-MenC antibody titres > or = 1:8 respectively. Seroprotection/seropositivity rates to the 5 antigens administered in the routine EPI schedule were non-inferior in children in the study group compared to those in the control group. The percentages of subjects in the study group with persisting SBA-MenA titres > or = 1:8 or SBA-MenC titres > or = 1:8 at the age of 12 months prior to challenge were significantly higher than in control group (47.7% vs 25.7% and 56.4% vs 5.1% respectively. The administration of 10 microg of serogroup A polysaccharide increased the SBA-MenA GMT by 14.0-fold in the DTPW-HBV/HibMenAC-group compared to a 3.8 fold increase in the control-group. Corresponding fold-increases in SBA-MenC titres following challenge with 10 microg of group C polysaccharide were 18.8 and 1.9 respectively. Reactogenicity following primary vaccination or the administration of the challenge dose was similar in both groups, except for swelling (Grade 3 after primary vaccination which was more
Full Text Available Manuel Rodriguez-Valle,1 Leonardo Canan-Hadden,2 Olivia Niebla2 1Animal Biotechnology Division, 2Analytical Division, Centre for Genetic Engineering and Biotechnology, Havana, Cuba Abstract: The ectoparasite Rhipicephalus (Boophilus microplus causes severe economic losses to the cattle industry in tropical and subtropical regions, and transmits endoparasites, such as Babesia bovis. The glycoprotein Bm95 is homologous to Bm86, a surface membrane protein of gut epithelial cells in R. microplus, and has been shown to efficiently control this ectoparasite in regions of the Americas. The immunostimulant properties of Bm86 have already been demonstrated after its coinjection with hepatitis B surface antigen (HBsAg and the infectious bovine rhinotracheitis virus. This study evaluated the carrier and immunostimulant properties of Bm95 using low immunogenic Neisseria meningitidis capsular C polysaccharide (Men CpS and HBsAg. We produced two polysaccharide-Bm95 conjugates by carbodiimide (MenCpSBm-c and reductive amination (MenCpSBm-ra methods. These conjugates were characterized and evaluated in mice. Antibody titers against Men CpS were significantly higher in mice immunized with MenCpSBm-ra (2,350±250, P<0.01 than in those immunized with MenCpSBm-c (250±75 or Men CpS (570±104. The study data indicate effective immunological memory after booster inoculation in mice immunized with MenCpSBm-ra. Additionally, significant humoral immunity against HBsAg was documented in mice coimmunized via the intranasal route with recombinant Bm95 (11,400±345 and HBsAg (128,000±250 compared with mice immunized only with HBsAg (400±40 or Bm95 (5,461±150, P<0.01. In conclusion, the immunostimulatory properties of recombinant Bm95 make it a useful element for developing safer conjugated vaccines against bacterial pathogens and for evaluation against ticks and tick-borne diseases in the context of a polyvalent veterinary vaccine. Keywords: glycoconjugate, Bm86
Cruces R, Pablo; Donoso F, Alejandro; Camacho A, Jorge; Llorente H, Marcela
After almost a decade since the introduction of Haemophilus influenzae type b (Hib) conjugate vaccines in Chile (in a 2-4-6 month schedule), Hib invasive infections have dramatically decreased, albeit they remain to occasionally produce disease in pediatric patients. We report our experience with children whom developed Hib invasive disease in children since 2000 to 2004. Medical records of children with Hib were reviewed in order to describe the epidemiology, main clinical and laboratory findings, management and complications. Twenty three patients (17 male), between 1 and 71 months (median 30 months) were identified: pneumonia (7), meningitis (4), pleuropneumonia (2), empyema (2), sepsis (2), cellulitis (2), meningitis and pleuropneumonia (1), purpura fulminans (1), miositis (1) and epiglottitis (1). No deaths were observed and four patients presented severe sequelae at hospital discharge. Twenty patients were considered vaccine failures. Hib remains as a sporadic cause of severe disease in Chile and thus for physicians should still keep it in mind. Case analysis and active surveillance are necessary to monitor the current immunization regimen.
van Ravenhorst, Mariëtte B; van der Klis, Fiona R M; van Rooijen, Debbie M; Sanders, Elisabeth A M; Berbers, Guy A M
Recently the incidence of meningococcal serogroup Y (MenY) and in particular serogroup W (MenW) invasive disease has risen in several European countries, including the Netherlands. Adolescents are a target group for primary prevention through vaccination to protect against disease and reduce
van Ravenhorst, Mariëtte B.; van der Klis, Fiona R M; van Rooijen, Debbie M; Sanders, Elisabeth A.M.; Berbers, Guy A M
Background Recently the incidence of meningococcal serogroup Y (MenY) and in particular serogroup W (MenW) invasive disease has risen in several European countries, including the Netherlands. Adolescents are a target group for primary prevention through vaccination to protect against disease and
Tregnaghi, Miguel W.; Sáez-Llorens, Xavier; López, Pio; Abate, Hector; Smith, Enrique; Pósleman, Adriana; Calvo, Arlene; Wong, Digna; Cortes-Barbosa, Carlos; Ceballos, Ana; Tregnaghi, Marcelo; Sierra, Alexandra; Rodriguez, Mirna; Troitiño, Marisol; Carabajal, Carlos; Falaschi, Andrea; Leandro, Ana; Castrejón, Maria Mercedes; Lepetic, Alejandro; Lommel, Patricia; Hausdorff, William P.; Borys, Dorota; Guiñazú, Javier Ruiz; Ortega-Barría, Eduardo; Yarzábal, Juan P.; Schuerman, Lode
Background The relationship between pneumococcal conjugate vaccine–induced antibody responses and protection against community-acquired pneumonia (CAP) and acute otitis media (AOM) is unclear. This study assessed the impact of the ten-valent pneumococcal nontypable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) on these end points. The primary objective was to demonstrate vaccine efficacy (VE) in a per-protocol analysis against likely bacterial CAP (B-CAP: radiologically confirmed CAP with alveolar consolidation/pleural effusion on chest X-ray, or non-alveolar infiltrates and C-reactive protein ≥ 40 µg/ml); other protocol-specified outcomes were also assessed. Methods and Findings This phase III double-blind randomized controlled study was conducted between 28 June 2007 and 28 July 2011 in Argentine, Panamanian, and Colombian populations with good access to health care. Approximately 24,000 infants received PHiD-CV or hepatitis control vaccine (hepatitis B for primary vaccination, hepatitis A at booster) at 2, 4, 6, and 15–18 mo of age. Interim analysis of the primary end point was planned when 535 first B-CAP episodes, occurring ≥2 wk after dose 3, were identified in the per-protocol cohort. After a mean follow-up of 23 mo (PHiD-CV, n = 10,295; control, n = 10,201), per-protocol VE was 22.0% (95% CI: 7.7, 34.2; one-sided p = 0.002) against B-CAP (conclusive for primary objective) and 25.7% (95% CI: 8.4%, 39.6%) against World Health Organization–defined consolidated CAP. Intent-to-treat VE was 18.2% (95% CI: 5.5%, 29.1%) against B-CAP and 23.4% (95% CI: 8.8%, 35.7%) against consolidated CAP. End-of-study per-protocol analyses were performed after a mean follow-up of 28–30 mo for CAP and invasive pneumococcal disease (IPD) (PHiD-CV, n = 10,211; control, n = 10,140) and AOM (n = 3,010 and 2,979, respectively). Per-protocol VE was 16.1% (95% CI: −1.1%, 30.4%; one-sided p = 0.032) against clinically confirmed AOM
Arya, Bikas K; Bhattacharya, Sangeeta Das; Sutcliffe, Catherine G; Ganaie, Feroze; Bhaskar, Arun; Bhattacharyya, Subhasish; Niyogi, Swapan Kumar; Moss, William J; Panda, Samiran; Ravikumar, Kadahalli Lingegowda; Das, Ranjan Saurav; Mandal, Sutapa
Human immunodeficiency virus (HIV) infection increases risk of invasive disease from Streptococcus pneumoniae. Pneumococcal conjugate vaccines (PCV) prevent invasive disease and acquisition of vaccine type (VT) pneumococcus in the nasopharynx. To look at the safety and impact of one dose of PCV13 on acquisition of VT pneumococcal carriage in Indian children with HIV. We conducted a cohort study in families of HIV-infected children (CLH) and families of HIV-uninfected children (HUC) in West Bengal. All children received one dose of PCV13. Nasopharyngeal swabs were collected from children and parents at baseline and 2 months after vaccination. One hundred and fifteen CLH and 47 HUC received one dose of PCV13. Fifty-eight percent of CLH were on antiretroviral therapy (ART), and the median nadir CD4 count was 287. There were no significant adverse events in either group. HUC had more VT colonization than CLH-55% versus 23% of all pneumococcal isolates. HIV infection doubled the risk of nonvaccine serotype colonization (P = 0.03). There was no difference in acquisition of VT isolates in CLH (4.4%) and HUC (4.5%) post-PCV13; however, older CLH (>5 years) had decreased clearance of VT strains. ART made no difference in pneumococcal colonization at baseline or after PCV13; however, CLH with higher nadir CD4 counts before starting ART were less likely to have VT colonization post-PCV13 (prevalence ratio, 0.2; 95% confidence interval: 0.1-0.5). While there was no difference in acquisition of VT nasopharyngeal carriage of pneumococcus in CLH and HUC after one dose of PCV13, earlier access to ART may impact response to PCV13 in CLH.
Full Text Available Carrier-specific T cell and polysaccharide-specific B cell memory responses are not well characterised in infants following glyco-conjugate vaccination. We aimed to determine if the number of Meningococcal (Men C- and Y- specific memory B cells and; number and quality of Tetanus Toxoid (TT carrier-specific memory CD4+ T cells are associated with polysaccharide-specific IgG post HibMenCY-TT vaccination. Healthy infants received HibMenCY-TT vaccine at 2, 4 and 6 months with a booster at 12 months. Peripheral blood mononuclear cells were isolated and polysaccharide-specific memory B cells enumerated using ELISpot. TT-specific memory CD4+ T cells were detected and phenotyped based on CD154 expression and intracellular TNF-α, IL-2 and IFN-γ expression following stimulation. Functional polysaccharide-specific IgG titres were measured using the serum bactericidal activity (SBA assay. Polysaccharide-specific Men C- but not Men Y- specific memory B cell frequencies pre-boost (12 months were significantly associated with post-boost (13 months SBA titres. Regression analysis showed no association between memory B cell frequencies post-priming (at 6 or 7 months and SBA at 12 months or 13 months. TT-specific CD4+ T cells were detected at frequencies between 0.001 and 0.112 as a percentage of CD3+ T cells, but their numbers were not associated with SBA titres. There were significant negative associations between SBA titres at M13 and cytokine expression at M7 and M12.Induction of persistent polysaccharide-specific memory B cells prior to boosting is an important determinant of secondary IgG responses in infants. However, polysaccharide-specific functional IgG responses appear to be independent of the number and quality of circulating carrier-specific CD4+ T cells after priming.
Boccalini, Sara; Azzari, Chiara; Resti, Massimo; Valleriani, Claudia; Cortimiglia, Martina; Tiscione, Emilia; Bechini, Angela; Bonanni, Paolo
A new 13-valent conjugated polysaccharide vaccine (PCV13) against Streptococcus pneumoniae infections, which replaced the 7-valent vaccine (PCV7) in the regional immunization programmes for newborns and children who started but not completed the 3 doses schedule of PCV7, is available in Italy since 2010. The opportunity of administering a further dose of PCV13 to children under 5 years of age who had already completed their vaccination with PCV7, with the aim of extending the serotype coverage, triggered an animated scientific debate. The purpose of this study was to perform a clinical/economic evaluation of the administration of a dose of PCV13, in a catch-up programme, for children under 5 years of age, who had already received 3 doses of PCV7. A mathematical model of the clinical/economic impact of the adoption of 4 catch-up strategies with PCV13 (children up to 24, 36, 48 and 60 months old) was set up, with a vaccination coverage of 80%, versus immunization with 3 doses of PCV7 without the catch-up programme. The time span covered by the simulation was 5.5 years. The following clinical outcomes of infection were evaluated: hospitalised meningitis/sepsis, hospitalised bacteraemic pneumonias (complicated and uncomplicated), hospitalised non-bacteraemic pneumonias, and non-hospitalised pneumonias. The administration of one dose of PCV13 to children up to 60 months of age significantly reduces the number of cases of pneumococcal diseases (especially, non-hospitalised pneumonias, 80% of all events prevented, and hospitalised cases of non-bacteraemic pneumococcal pneumonias, 15% of all events prevented) and, subsequently, the relative cost for medical treatment. This results in savings for medical costs amounting to more than 1,000,000 Euros when vaccinating children under 24 months of age (up to almost 3 million Euros for children up to 60 months). More than half of those savings are attributable to avoided hospitalised cases of non-bacteraemic pneumococcal
Bellver Capella, Vincente
Vaccines are an extraordinary instrument of immunization of the population against infectious diseases. Around them there are many ethical issues. One of the most debated is what to do with certain groups opposition to vaccination of their children. States have managed in different ways the conflict between the duty of vaccination and the refusal to use vaccines: some impose the vaccination and others simply promote it. In this article we deal with which of these two approaches is the most suitable from an ethical and legal point of view. We stand up for the second option, which is the current one in Spain, and we propose some measures which should be kept in mind to improve immunization programs.
Liu, Bin; Frost, Jeffrey L; Sun, Jing; Fu, Hongjun; Grimes, Stephen; Blackburn, Peter; Lemere, Cynthia A
Active amyloid-β (Aβ) immunotherapy is under investigation to prevent or treat early Alzheimer's disease (AD). In 2002, a Phase II clinical trial (AN1792) was halted due to meningoencephalitis in ∼6% of the AD patients, possibly caused by a T-cell-mediated immunological response. Thus, generating a vaccine that safely generates high anti-Aβ antibody levels in the elderly is required. In this study, MER5101, a novel conjugate of Aβ1-15 peptide (a B-cell epitope fragment) conjugated to an immunogenic carrier protein, diphtheria toxoid (DT), and formulated in a nanoparticular emulsion-based adjuvant, was administered to 10-month-old APPswe/PS1ΔE9 transgenic (Tg) and wild-type (Wt) mice. High anti-Aβ antibody levels were observed in both vaccinated APPswe/PS1ΔE9 Tg and Wt mice. Antibody isotypes were mainly IgG1 and IgG2b, suggesting a Th2-biased response. Restimulation of splenocytes with the Aβ1-15:DT conjugate resulted in a strong proliferative response, whereas proliferation was absent after restimulation with Aβ1-15 or Aβ1-40/42 peptides, indicating a cellular immune response against DT while avoiding an Aβ-specific T-cell response. Moreover, significant reductions in cerebral Aβ plaque burden, accompanied by attenuated microglial activation and increased synaptic density, were observed in MER5101-vaccinated APPswe/PS1ΔE9 Tg mice compared with Tg adjuvant controls. Last, MER5101-immunized APPswe/PS1ΔE9 Tg mice showed improvement of cognitive deficits in both contextual fear conditioning and the Morris water maze. Our novel, highly immunogenic Aβ conjugate vaccine, MER5101, shows promise for improving Aβ vaccine safety and efficacy and therefore, may be useful for preventing and/or treating early AD.
Farmaki, Paraskevi F; Chini, Maria C; Mangafas, Nikolaos M; Tzanoudaki, Marianna T; Piperi, Christina P; Lazanas, Marios Z; Spoulou, Vana S
Vaccine-induced memory B-cell (MBC) subsets have distinct roles in the establishment of protective immunity; MBCs expressing nonswitched immunoglobulin M (IgM+ MBCs) replenish the MBC pool, whereas MBCs expressing isotype-switched immunoglobulin (sIg+ MBCs) differentiate into plasma cells upon antigen reencounter. We investigated immunogenicity and MBCs induced by combined 13-valent pneumococcal conjugate vaccine (PCV13) and 23-valent pneumococcal polysaccharide vaccine (PPV23) in human immunodeficiency virus (HIV)-infected adults. Forty HIV-seropositive adults receiving ART with undetectable viral loads were enrolled. Seventeen had a CD4+ T-cell count of ≥400 cells/μL (group A), and 23 had a CD4+ T-cell count of 200-399 cells/μL (group B). All adults received PCV13 and, 1 year later, PPV23. Levels of IgM+ MBCs (defined as polysaccharide [PS]-specific CD19+CD10-CD27+CD21++IgM+ MBCs) and sIg+ MBCs (defined as PS-specific CD19+CD10-CD27+CD21++IgM- MBCs) and antibodies against PS14 and PS3 were measured prior and 1 month after each vaccination. Immunization caused a significant increase in PS antibodies, compared with levels at baseline (P < .001). Group B achieved significantly lower titers than group A (P < .05 for both PS14 and PS3). After receipt of PCV13, levels of IgM+ MBCs were unchanged, whereas levels of sIg+ MBCs increased significantly (P < .05 for PS14 and P < .001 for PS3). In contrast, following PPV23 receipt, levels of IgM+ MBCs were significantly reduced, and levels of sIg+ MBCs remained stable. A positive correlation was observed between baseline IgM+ and sIg+ MBC counts 1 month after PCV13 receipt but not after PPV23 receipt. PPV23 receipt 12 months after PCV13 receipt improved PCV13 immunogenicity. The reduction in the IgM+ MBC count observed after PPV23 receipt suggests that PPV23 has a depleting effect on PCV13-associated immunological memory. NCT03041051.
Alienke J Wijmenga-Monsuur
Full Text Available Since 2009/10, a 10- and a 13-valent pneumococcal conjugate vaccine (PCV are available, but only the 10-valent vaccine is now being used for the children in the Netherlands. As the vaccines differ in number of serotypes, antigen concentration, and carrier proteins this study was designed to directly compare quantity and quality of the antibody responses induced by PCV10 and PCV13 before and after the 11-month booster.Dutch infants (n = 132 were immunized with either PCV10 or PCV13 and DTaP-IPV-Hib-HepB at the age of 2, 3, 4 and 11 months. Blood samples were collected pre-booster and post-booster at one week and one month post-booster for quantitative and qualitative immunogenicity against 13 pneumococcal serotypes, as well as quantitative immunogenicity against diphtheria, tetanus, pertussis and Haemophilus influenzae type b. We compared immunogenicity induced by PCV13 and PCV10 for their ten shared serotypes.One month post-booster, pneumococcal serotype-specific IgG geometric mean concentrations (GMCs for the PCV13 group were higher compared with the PCV10 group for six serotypes, although avidity was lower. Serotype 19F showed the most distinct difference in IgG and, in contrast to other serotypes, its avidity was higher in the PCV13 group. One week post-booster, opsonophagocytosis for serotype 19F did not differ significantly between the PCV10- and the PCV13 group.Both PCV10 and PCV13 were immunogenic and induced a booster response. Compared to the PCV10 group, the PCV13 group showed higher levels for serotype 19F GMCs and avidity, pre- as well as post-booster, although opsonophagocytosis did not differ significantly between groups. In our study, avidity is not correlated to opsonophagocytotic activity (OPA and correlations between IgG and OPA differ per serotype. Therefore, besides assays to determine IgG GMCs, assays to detect opsonophagocytotic activity, i.e., the actual killing of the pneumococcus, are important for PCV evaluation. How
Jiang, Yiling; Gauthier, Aline; Keeping, Sam; Carroll, Stuart
Since the introduction of the routine childhood immunization, a change in epidemiology of pneumococcal disease has been seen in both children and adults. This study aimed to quantify the public health and budget impact of pneumococcal vaccination of the elderly and those in at risk groups in the UK. The model was adapted from a previous population-based Markov model. At-risk adults and the elderly were assumed to receive PPV23 or PCV13 vaccination or no vaccination. Over the study period (2012-2016), PPV23 vaccination led to a reduction in the number of invasive pneumococcal disease cases in most scenarios. The net budget impact ranged between £15 and £39 million (vs no vaccination) or between -£116 and -£93 million (vs PCV13). PPV23 vaccination program remains the optimal strategy from public health and budgetary perspectives despite epidemiological changes. PCV13 is likely to impose a significant budget with limited health benefits.
Immunogenicity and Safety of 10-valent Pneumococcal Nontypeable Haemophilus influenzae Protein D Conjugate Vaccine (PHiD-CV) Administered to Children With Sickle Cell Disease Between 8 Weeks and 2 Years of Age: A Phase III, Open, Controlled Study.
Sirima, Sodiomon B; Tiono, Alfred; Gansané, Zakaria; Siribié, Mohamadou; Zongo, Angèle; Ouédraogo, Alphonse; François, Nancy; Strezova, Ana; Dobbelaere, Kurt; Borys, Dorota
Immunogenicity, safety and reactogenicity of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) were evaluated in children with sickle cell disease (SCD), who are at increased risk for infections. In this phase III, open-label, single-center, controlled study in Burkina Faso (NCT01175083), children with SCD (S) or without SCD (NS) were assigned to 6 groups (N = 300): children 8-11 weeks of age (vaccines; children 7-11 months of age (7-11S and 7-11NS groups) received 2 primary doses and a booster dose of PHiD-CV; children 12-23 months of age (12-23S and 12-23NS groups) received 2 catch-up doses of PHiD-CV. Pneumococcal antibody responses were measured using 22F-inhibition enzyme-linked immunosorbent assay and functional opsonophagocytic activity. Responses to other antigens were measured by enzyme-linked immunosorbent assay. Adverse events were recorded. One month postprimary vaccination, for each vaccine serotype ≥98% of infants in the vaccination in children vaccination. Safety and reactogenicity profiles were similar in children with or without SCD. PHiD-CV was immunogenic with an acceptable safety profile in children with and without SCD starting vaccination at 8 weeks to 23 months of age.
Lai, Zengzu; Schreiber, John R
Pneumococcal (Pn) polysaccharides (PS) are T-independent (TI) antigens and do not induce immunological memory or antibodies in infants. Conjugation of PnPS to the carrier protein CRM(197) induces PS-specific antibody in infants, and memory similar to T-dependent (Td) antigens. Conjugates have improved immunogenicity via antigen processing and presentation of carrier protein with MHC II and recruitment of T cell help, but the fate of the PS attached to the carrier is unknown. To determine the location of the PS component of PnPS-CRM(197) in the APC, we separately labeled PS and protein and tracked their location. The PS of types 14-CRM(197) and 19F-CRM(197) was specifically labeled by Alexa Fluor 594 hydrazide (red). The CRM(197) was separately labeled red in a reaction that did not label PS. Labeled antigens were incubated with APC which were fixed, permeabilized and incubated with anti-MHC II antibody labeled green by Alexa Fluor 488, followed by confocal microscopy. Labeled CRM(197) was presented on APC surface and co-localized with MHC II (yellow). Labeled unconjugated 14 or 19F PS did not go to the APC surface, but PS labeled 14-CRM(197) and 19F-CRM(197) was internalized and co-localized with MHC II. Monoclonal antibody to type 14 PS bound to intracellular type 14 PS and PS-CRM(197). Brefeldin A and chloroquine blocked both CRM(197) and PS labeled 14-CRM(197) and 19F-CRM(197) from co-localizing with MHC II. These data suggest that the PS component of the CRM(197) glycoconjugate enters the endosome, travels with CRM(197) peptides to the APC surface and co-localizes with MHC II.
Immunogenicity, Safety and Reactogenicity of a Booster Dose of the 10-Valent Pneumococcal Nontypeable H. influenzae Protein D Conjugate Vaccine Coadministered With DTPa-IPV-Hib in Dutch Children: A Randomized Controlled Trial.
van den Bergh, Menno R; Spijkerman, Judith; François, Nancy; Swinnen, Kristien; Borys, Dorota; Schuerman, Lode; Veenhoven, Reinier H; Sanders, Elisabeth A M
Immune responses and safety profiles may be affected when vaccines are coadministered. We evaluated the immunogenicity, safety and reactogenicity of a booster dose of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D-conjugate (PHiD-CV; Synflorix GSK Vaccines) and DTPa-IPV-Hib (Pediacel Sanofi Pasteur MSD) when coadministered. We performed booster assessment in a randomized controlled trial in the Netherlands. Of 780 enrolled healthy infants, 774 toddlers participated in the booster phase and received (1:1:1) (1) PHiD-CV + DTPa-HBV-IPV/Hib (Infanrix hexa, GSK Vaccines), (2) PHiD-CV + DTPa-IPV-Hib, or (3) 7-valent pneumococcal conjugate vaccine (7vCRM, Prevenar/Prevnar, Pfizer, Inc.) + DTPa-IPV-Hib at 2, 3, 4 and 11-13 months old. Blood samples were taken postprimary, prebooster, 1 and 12 months postbooster. Antipneumococcal antibody responses were comparable between both PHiD-CV groups, except for serotype 18C (conjugated to tetanus toxoid). Anti-18C antibody geometric mean concentrations (GMCs) were higher when coadministered with DTPa-HBV-IPV/Hib. For each vaccine serotype, the percentages of children with antibody concentration ≥ 0.20 μg/mL were within the same ranges between PHiD-CV groups (93.8%-100%). The same was observed for the percentages of participants with opsonophagocytic activity titer ≥ 8 (90.9%-100%). When comparing both DTPa-IPV-Hib groups, postbooster antidiphtheria antibody GMCs were higher when coadministered with 7vCRM, while antitetanus and antipolyribosyl-ribitol phosphate antibody GMCs were higher with PHiD-CV coadministration. Regardless, antibody levels to these antigens were well above thresholds. Safety and reactogenicity profiles were comparable between groups. Coadministration of a booster dose of PHiD-CV and DTPa-IPV-Hib was immunogenic and well tolerated.
Ladhani, Shamez N; Ramsay, Mary; Borrow, Ray; Riordan, Andrew; Watson, John M; Pollard, Andrew J
In 2015, the UK became the first country in the world to have a comprehensive routine meningococcal vaccine programme targeting all of the main capsular groups of N. meningitidis. 1 An infant vaccine programme against meningococcal capsular group B Neisseria meningitidis (MenB) was launched from 1st September with an aim to reduce endemic MenB disease in early childhood. On 1st August 2015, an adolescent programme against groups A, C, W and Y meningococci (MenACWY) was rolled out to halt a gr...
Arya, Bikas K; Bhattacharya, Sangeeta Das; Sutcliffe, Catherine G; Saha, Malay K; Bhattacharyya, Subhasish; Niyogi, Swapan Kumar; Moss, William J; Panda, Samiran; Das, Ranjan Saurav; Mallick, Mausom; Mandal, Sutapa
Children living with HIV are at increased risk of disease from Haemophilus influenzae type b (Hib). Data are limited on the immunogenicity of a two-dose, catch-up schedule for Hib conjugate vaccine (HibCV) among HIV-infected children accessing antiretroviral therapy (ART) late. The objectives of the study were to: (1) evaluate baseline immunity to Hib and the immunogenicity and safety of two doses of HibCV among HIV-infected Indian children; and (2) document the threshold antibody level required to prevent Hib colonization among HIV-infected children following immunization. We conducted a prospective cohort study among HIV-infected children 2-15 years of age and HIV-uninfected children 2-5 years of age. HIV-infected children received two doses of HibCV and uninfected children received one. Serum anti-Hib PRP IgG antibodies were measured at baseline and two months after immunization in the HIV-infected children. Nasopharyngeal (NP) swabs were collected at baseline and follow-up. 125 HIV-infected and 44 uninfected children participated. 40% of HIV-infected children were receiving ART and 26% had a viral load >100,000 copies/mL. The geometric mean concentration of serum anti-Hib PRP antibody increased from 0.25 μg/mL at baseline to 2.65 μg/mL after two doses of HibCV, representing a 10.6-fold increase (pchildren mounted an immune response. Moderate or severe immune suppression, trimethoprim/sulfamethoxazole prophylaxis, and lower baseline antibody levels were associated with lower post-vaccine serum anti-Hib PRP IgG antibodies. A serum anti-Hib PRP IgG antibody level ≥ 3.3 μg/mL was protective against Hib NP colonization. There were no differences in adverse events between HIV-infected and uninfected children. Including a catch-up immunization schedule for older HIV infected children in countries introducing Hib vaccines is important. Older HIV-infected children with delayed access to ART and without suppressed viral loads mounted an adequate immune response
Immunogenicity, safety and reactogenicity of the pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in 2-17-year-old children with asplenia or splenic dysfunction: A phase 3 study.
Szenborn, L; Osipova, I V; Czajka, H; Kharit, S M; Jackowska, T; François, N; Habib, M A; Borys, D
Immunization with pneumococcal vaccines is an important prophylactic strategy for children with asplenia or splenic dysfunction, who are at high risk of bacterial infections (including S. pneumoniae). This study aimed to assess immunogenicity and safety of pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV, GSK) in this at-risk population. This phase III, multi-centre, open-label, controlled study, in which at-risk children with asplenia or splenic dysfunction were enrolled (age strata: 2-4, 5-10 and 11-17years), was conducted in Poland and the Russian Federation. For the 2-4years at-risk group, healthy age-matched children were enrolled as control. Unprimed children (not previously vaccinated with any pneumococcal vaccine) received 2 PHiD-CV doses (≥2months apart) and pneumococcal vaccine-primed children received 1 dose. Immune responses were assessed pre-vaccination and one month post-each dose. Solicited and unsolicited adverse events (AEs) were recorded for 4 and 31days post-vaccination, respectively, and serious AEs (SAEs) throughout the study. Of 52 vaccinated children (18 at-risk primed, 28 at-risk unprimed and 6 control unprimed), 45 (18, 23 and 4, respectively) were included in the according-to-protocol cohort for immunogenicity. Post-vaccination (post-dose 1 in primed and post-dose 2 in unprimed children), for each vaccine pneumococcal serotype and vaccine-related serotype 6A all at-risk children had antibody concentrations ≥0.2µg/mL, and for vaccine-related serotype 19A at least 94.4%. Increases in antibody geometric mean concentrations were observed. For most serotypes, all at-risk children had post-vaccination opsonophagocytic activity (OPA) titers ≥8 and increases in OPA geometric mean titers were observed. No safety concerns were raised. One non-fatal SAE (respiratory tract infection, considered not vaccine-related) was reported by one at-risk unprimed child. PHiD-CV was immunogenic and well tolerated in 2
McCollum, Eric D.; Nambiar, Bejoy; Deula, Rashid; Zadutsa, Beatiwel; Bondo, Austin; King, Carina; Beard, James; Liyaya, Harry; Mankhambo, Limangeni; Lazzerini, Marzia; Makwenda, Charles; Masache, Gibson; Bar-Zeev, Naor; Kazembe, Peter N.; Mwansambo, Charles; Lufesi, Norman; Costello, Anthony; Armstrong, Ben
Background The pneumococcal conjugate vaccine’s (PCV) impact on childhood pneumonia during programmatic conditions in Africa is poorly understood. Following PCV13 introduction in Malawi in November 2011, we evaluated the case burden and rates of childhood pneumonia. Methods and Findings Between January 1, 2012-June 30, 2014 we conducted active pneumonia surveillance in children pneumonia per Malawi guidelines, defined as fast breathing only, chest indrawing +/- fast breathing, or, ≥1 clinical danger sign. Since pulse oximetry was not in the Malawi guidelines, oxygenation pneumonia, a distinct category from clinical pneumonia. We quantified the pneumonia case burden and rates in two ways. We compared the period immediately following vaccine introduction (early) to the period with >75% three-dose PCV13 coverage (post). We also used multivariable time-series regression, adjusting for autocorrelation and exploring seasonal variation and alternative model specifications in sensitivity analyses. The early versus post analysis showed an increase in cases and rates of total, fast breathing, and indrawing pneumonia and a decrease in danger sign and hypoxemic pneumonia, and pneumonia mortality. At 76% three-dose PCV13 coverage, versus 0%, the time-series model showed a non-significant increase in total cases (+47%, 95% CI: -13%, +149%, p = 0.154); fast breathing cases increased 135% (+39%, +297%, p = 0.001), however, hypoxemia fell 47% (-5%, -70%, p = 0.031) and hospital deaths decreased 36% (-1%, -58%, p = 0.047) in children pneumonia, including hypoxemia and death, have markedly decreased. PMID:28052071
Haro, Kaoru; Ogawa, Masato; Hoshina, Takayuki; Kojiro, Masumi; Kusuhara, Koichi
This study aimed to compare hospitalization of children for pneumonia between secondary and tertiary medical facilities, which hospitalize many children without and with underlying diseases, respectively, after the introduction of the pneumococcal conjugate vaccine (PCV). Our retrospective study included children admitted to the Department of Pediatrics at Kitakyushu General Hospital, a secondary medical facility, and the Hospital of the University of Occupational and Environment Health, Japan, a tertiary medical facility, from 2009 to 2013 for pneumonia. We compared the change in the rate of hospitalization for pneumonia after the introduction of the 7-valent PCV between the secondary and tertiary medical facilities. Hospitalization of patients with pneumonia declined by 28.8% in our secondary medical facility. In particular, hospitalization for pneumonia other than confirmed mycoplasmal or viral pneumonia was significantly reduced by 49.2%. In contrast, hospitalization of patients with pneumonia did not decline in our tertiary medical facility. After the introduction of PCV, hospitalization of children for pneumonia was not reduced at the tertiary medical facility. Various other pathogens besides pneumococcus may be associated with the development of pneumonia in children with underlying diseases.
Safety and immunogenocity of a novel combined Haemophilus influenzae type b-Neisseria meningitidis serogroups A and C-tetanus-toxoid conjugate vaccine in healthy Chinese children aged 6 months to 5 years old.
Hu, Jian-li; Tao, Hong; Li, Jing-xin; Dai, Wei-ming; Song, Bin; Sun, Jin-fang; Liu, Pei; Tang, Jie; Liu, Wen-yu; Wang, Shi-yuan; Zhu, Feng-cai
A novel combined Haemophilus influenzae type b-Neisseria meningitidis serogroups A and C-tetanus-toxoid conjugate vaccine (Hib-MenAC vaccine) has been developed to protect children against diseases caused by Hib, MenA, and MenC. This study investigated the safety and immunogenicity of the Hib-MenAC vaccine administered in 2-dose series to children aged 6-23 months and in a single dose to children aged 2-5 y. A randomized, positive-controlled, non-inferiority clinical trial was conducted for 1200 healthy participants in each age group. Within each age group, participants were randomly allocated to the Hib-MenAC group or the control group at a ratio of 1:1. Adverse reactions were recorded within 28 d after each dose. Blood samples were obtained to assess immunogenicity on day 0 and at 28 d after a complete vaccination course. For the investigational vaccine, the incidence of total adverse reactions in vaccinees aged 6-23 months was 46.8% and that in vaccinees aged 2-5 y was 29.8%. Most adverse reactions were mild or moderate. One non-fatal serious adverse event occurred in the Hib-MenAC group, but was unrelated to vaccination. The seroconversion rate to the 3 components reached 94.0%, and the proportion of vaccinees with rSBA titers ≥ 1:8 and PRP ≥ 0.15 g/mL reached 97.0% in both age groups. The safety and immunogenicity of the Hib-MenAC vaccine were non-inferior when compared to the licensed vaccines. It was concluded that the novel vaccine would be expected to protect children against all of the targeted diseases.
Full Text Available We measured meningococcal serogroup C (MenC-specific memory B-cell responses in infants by Enzyme-Linked Immunospot (ELISpot following different MenC conjugate vaccine schedules to investigate the impact of priming on immune memory.Infants aged 2 months were randomised to receive 1 or 2 doses of MenC-CRM197 at 3 or 3 and 4 months, 1 dose of MenC-TT at 3 months, or no primary MenC doses. All children received a Haemophilus influenzae type b (Hib-MenC booster at 12 months. Blood was drawn at 5, 12, 12 months +6 days and 13 months of age.Results were available for 110, 103, 76 and 44 children from each group respectively. Following primary immunisations, and prior to the 12-month booster, there were no significant differences between 1- or 2-dose primed children in the number of MenC memory B-cells detected. One month following the booster, children primed with 1 dose MenC-TT had more memory B-cells than children primed with either 1-dose (p = 0.001 or 2-dose (p<0.0001 MenC-CRM197. There were no differences in MenC memory B-cells detected in children who received 1 or 2 doses of MenC-CRM197 in infancy and un-primed children.MenC-specific memory B-cell production may be more dependent on the type of primary vaccine used than the number of doses administered. Although the mechanistic differences between MenC-CRM197 and MenC-TT priming are unclear, it is possible that structural differences, including the carrier proteins, may underlie differential interactions with B- and T-cell populations, and thus different effects on various memory B-cell subsets. A MenC-TT/Hib-MenC-TT combination for priming/boosting may offer an advantage in inducing more persistent antibody.EU Clinical Trials Register 2009-016579-31 ClinicalTrials.gov NCT01129518.
Jennifer R Verani
Full Text Available Nasopharyngeal carriage is a precursor for pneumococcal disease and can be useful for evaluating pneumococcal conjugate vaccine (PCV impact. We studied pre-PCV pneumococcal carriage among HIV-infected and -uninfected children in Mozambique. Between October 2012 and March 2013, we enrolled HIV-infected children age <5 years presenting for routine care at seven HIV clinics in 3 sites, including Maputo (urban-south, Nampula (urban-north, and Manhiça (rural-south. We also enrolled a random sample of HIV-uninfected children <5 years old from a demographic surveillance site in Manhiça. A single nasopharyngeal swab was obtained and cultured following enrichment in Todd Hewitt broth with yeast extract and rabbit serum. Pneumococcal isolates were serotyped by Quellung reaction and multiplex polymerase chain reaction. Factors associated with pneumococcal carriage were examined using logistic regression. Overall pneumococcal carriage prevalence was 80.5% (585/727, with similar prevalences among HIV-infected (81.5%, 339/416 and HIV-uninfected (79.1%, 246/311 children, and across age strata. Among HIV-infected, after adjusting for recent antibiotic use and hospitalization, there was no significant association between study site and colonization: Maputo (74.8%, 92/123, Nampula (83.7%, 82/98, Manhiça (84.6%, 165/195. Among HIV-uninfected, report of having been born to an HIV-infected mother was not associated with colonization. Among 601 pneumococcal isolates from 585 children, serotypes 19F (13.5%, 23F (13.1%, 6A (9.2%, 6B (6.2% and 19A (5.2% were most common. The proportion of serotypes included in the 10- and 13-valent vaccines was 44.9% and 61.7%, respectively, with no significant differences by HIV status or age group. Overall 36.9% (n = 268 of children were colonized with a PCV10 serotype and 49.7% (n = 361 with a PCV13 serotype. Pneumococcal carriage was common, with little variation by geographic region, age, or HIV status. PCV10 was introduced in
LaForce, F Marc; Konde, Kader; Viviani, Simonetta; Préziosi, Marie-Pierre
Epidemic meningococcal meningitis is an important public health problem in sub-Saharan Africa. Current control measures rely on reactive immunizations with polysaccharide (PS) vaccines that do not induce herd immunity and are of limited effectiveness in those under 2 years of age. Conversely, polysaccharide conjugate vaccines are effective in infants and have consistently shown an important effect on decreasing carriage, two characteristics that facilitate disease control. In 2001 the Meningitis Vaccine Project (MVP) was created as a partnership between PATH and the World Health Organization (WHO) with the goal of eliminating meningococcal epidemics in Africa through the development, licensure, introduction, and widespread use of conjugate meningococcal vaccines. Since group A Neisseria meningitidis (N. meningitidis) is the dominant pathogen causing epidemic meningitis in Africa MVP is developing an affordable (US$ 0.40 per dose) meningococcal A (Men A) conjugate vaccine through an innovative international partnership that saw transfer of a conjugation and fermentation technology to a developing country vaccine manufacturer. A Phase 1 study of the vaccine in India has shown that the product is safe and immunogenic. Phase 2 studies have begun in Africa, and a large demonstration study of the conjugate vaccine is envisioned for 2008-2009. After extensive consultations with African public health officials a vaccine introduction plan has been developed that includes introduction of the Men A conjugate vaccine into standard Expanded Programme on Immunization (EPI) schedules but also emphasizes mass vaccination of 1-29 years old to induce herd immunity, a strategy that has been shown to be highly effective when the meningococcal C (Men C) conjugate vaccine was introduced in several European countries. The MVP model is a clear example of the usefulness of a "push mechanism" to finance the development of a needed vaccine for the developing world.
A Cholera Conjugate Vaccine Containing O-specific Polysaccharide (OSP of V. cholerae O1 Inaba and Recombinant Fragment of Tetanus Toxin Heavy Chain (OSP:rTTHc Induces Serum, Memory and Lamina Proprial Responses against OSP and Is Protective in Mice.
Md Abu Sayeed
Full Text Available Vibrio cholerae is the cause of cholera, a severe watery diarrhea. Protection against cholera is serogroup specific. Serogroup specificity is defined by the O-specific polysaccharide (OSP component of lipopolysaccharide (LPS.Here we describe a conjugate vaccine for cholera prepared via squaric acid chemistry from the OSP of V. cholerae O1 Inaba strain PIC018 and a recombinant heavy chain fragment of tetanus toxin (OSP:rTTHc. We assessed a range of vaccine doses based on the OSP content of the vaccine (10-50 μg, vaccine compositions varying by molar loading ratio of OSP to rTTHc (3:1, 5:1, 10:1, effect of an adjuvant, and route of immunization.Immunized mice developed prominent anti-OSP and anti-TT serum IgG responses, as well as vibriocidal antibody and memory B cell responses following intramuscular or intradermal vaccination. Mice did not develop anti-squarate responses. Intestinal lamina proprial IgA responses targeting OSP occurred following intradermal vaccination. In general, we found comparable immune responses in mice immunized with these variations, although memory B cell and vibriocidal responses were blunted in mice receiving the highest dose of vaccine (50 μg. We found no appreciable change in immune responses when the conjugate vaccine was administered in the presence or absence of immunoadjuvant alum. Administration of OSP:rTTHc resulted in 55% protective efficacy in a mouse survival cholera challenge model.We report development of an Inaba OSP:rTTHc conjugate vaccine that induces memory responses and protection against cholera in mice. Development of an effective cholera conjugate vaccine that induces high level and long-term immune responses against OSP would be beneficial, especially in young children who respond poorly to polysaccharide antigens.
Immunogenicity and safety of the Vi-CRM197 conjugate vaccine against typhoid fever in adults, children, and infants in south and southeast Asia: results from two randomised, observer-blind, age de-escalation, phase 2 trials.
Bhutta, Zulfiqar A; Capeding, Maria Rosario; Bavdekar, Ashish; Marchetti, Elisa; Ariff, Shabina; Soofi, Sajid B; Anemona, Alessandra; Habib, Muhammad A; Alberto, Edison; Juvekar, Sanjay; Khan, Rana M Qasim; Marhaba, Rachid; Ali, Noshad; Malubay, Nelia; Kawade, Anand; Saul, Allan; Martin, Laura B; Podda, Audino
Typhoid vaccination is a public health priority in developing countries where young children are greatly affected by typhoid fever. Because present vaccines are not recommended for children younger than 2 years, the Novartis Vaccines Institute for Global Health developed a conjugate vaccine (Vi-CRM197) for infant immunisation. We aimed to assess the immunogenicity and safety of Vi-CRM197 in participants of various ages in endemic countries in south and southeast Asia. We did two randomised, observer-blind, age de-escalation, phase 2 trials at two sites in Pakistan and India (study A), and at one site in the Philippines (study B), between March 2, 2011, and Aug 9, 2012. Adults aged 18-45 years, children aged 24-59 months, older infants aged 9-12 months, and infants aged 6-8 weeks were randomly assigned (1:1) with a computer-generated randomisation list (block size of four) to receive either 5 μg Vi-CRM197 or 25 μg Vi-polysaccharide vaccine (or 13-valent pneumococcal conjugate vaccine in children younger than 2 years). Both infant populations received Vi-CRM197 concomitantly with vaccines of the Expanded Programme on Immunization (EPI), according to WHO schedule. With the exception of designated study site personnel responsible for vaccine preparation, study investigators, those assessing outcomes, and data analysts were masked to treatment allocation. We specified no a-priori null hypothesis for the immunogenicity or safety objectives and all analyses were descriptive. Analyses were by modified intention-to-treat. These studies are registered with ClinicalTrials.gov, numbers NCT01229176 and NCT01437267. 320 participants were enrolled and vaccinated in the two trials: 200 in study A (all age groups) and 120 in study B (children and infants only), of whom 317 (99%) were included in the modified intention-to-treat analysis. One dose of Vi-CRM197 significantly increased concentrations of anti-Vi antibody in adults (from 113 U/mL [95% CI 67-190] to 208 U/mL [117
Mäkelä, P. Helena; Siber, George R; Klugman, Keith P
... of Streptococcus pneumoniae with Complement Proteins 83 Margaret K. Hostetter III. Clinical Disease and Epidemiology 8 Epidemiology, Diagnosis, and Treatment of Serious Pneumococcal Infections in Chi...
Full Text Available OBJECTIVE: To compare the costs and benefits of pneumococcal conjugate vaccination compared with no vaccination from the perspectives of the health care system and society. METHODS: Using data from established sources, we estimated the incidence and mortality due to invasive pneumococcal disease, pneumonia, and acute otitis media (AOM for a hypothetical birth cohort of children from birth to 5 years. RESULTS: A universal pneumococcal conjugate vaccination program was estimated capable of annually avoiding 1 047 cases of invasive disease, 58 226 cases of pneumonia, and 209 862 cases of AOM. When herd immunity effects were considered, the program prevented 1.3 million cases of pneumococcal disease and over 7 000 pneumococcal deaths. At a vaccination cost of R$ 51.12 (US$ 26.35 per dose, vaccination would cost annually R$ 4 289 (US$ 2,211 per disability-adjusted life years averted. This does not take into account herd immunity effects. CONCLUSIONS: At the current vaccine price, conjugate vaccination could be a cost-effective investment compared to other options to control childhood diseases. Further analysis is required to determine whether vaccination at the current price is affordable to Brazil.OBJETIVO: Comparar los costos y los beneficios de la aplicación de la vacuna conjugada antineumocócica en comparación con la no vacunación, desde las perspectivas del sistema de salud y la sociedad. MÉTODOS: A partir de fuentes reconocidas, se estimaron la incidencia y la mortalidad por enfermedad neumocócica invasora, neumonía y otitis media aguda (OMA para una cohorte hipotética de niños desde su nacimiento hasta los 5 años. RESULTADOS: Se estimó que un programa de vacunación universal con una vacuna conjugada antineumocócica sería capaz de evitar anualmente 1 047 casos de la enfermedad invasora, 58 226 casos de neumonía y 209 862 casos de OMA. Si se considera el efecto de la inmunidad de grupo, el programa evitaría 1,3 millones de casos
Espinosa-Viñals, Carlos; García-Rivera, Dagmar; Rodríguez Noda, Laura; Amador Gómez, Aylín; Nicot, Milagros; Valle, Orialys; Núñez, Juan F; Martin, Yanet; Santana, Darielys; Valdés, Yury; Vérez Bencomo, Vicente
Finlay Vaccine Institute is developing a new heptavalent conjugate vaccine against Streptococcus pneumoniae. As infants are the target population, PCV7-TT will be necessarily co-administered with other vaccines, and then, the interactions represent a concern. The aim of this work is to evaluate the possible immunological interferences in rabbits as animal experimental model. Rabbits were immunized with Heberpenta®-L, VA-MENGOC-BC®, and PCV7-TT. Blood samples were taken fourteen days after final immunization for obtaining sera. Antibody responses to all antigens were evaluated by indirect ELISA. Functional responses against diphtheria and tetanus toxoid were done by in vivo seroneutralization assay. No interference was observed by PCV7-TT over the humoral response against diphtheria toxoid and meningococcal antigens (p > 0.05). A nonstatistically significant reduction (p > 0.05) was observed in the case of the humoral response against Haemophilus influenzae type b oligosaccharide. Concomitant administration of Heberpenta®-L and PCV7-TT increased twice the antibody titers as well as the protective activity against tetanus toxoid, but no statistical differences were found. The co-administration did not induce a reduction in the percent of responders against pneumococcal polysaccharides contained in PCV7-TT vaccine. Concomitant administration of PCV7-TT did not induce interferences over the evaluated antigens of Heberpenta®-L and VA-MENGOC-BC®. Also, no interference was observed on the immune response elicited by PCV7-TT. These preclinical results suggest that PCV7-TT will not result in a serious problem over the immune response elicited by the licensed vaccines Heberpenta®-L and VA-MENGOC-BC®. However, the clinical interference could be strictly studied during clinical trials in infants.
Gian Vincenzo Zuccotti
Full Text Available Streptococcus pneumoniae (SP is a gram-positive bacterium with more than 90 known serotypes causing around 11% of all deaths worldwide in children aged 1-59 months. A new era in prevention of SP-related diseases started in at the beginning of 2000s when a 7-valent pneumococcal conjugate vaccine (PCV7 was recommended as the vaccine of choice in pediatric age. PCV7 dramatically reduced invasive pneumococcal diseases (IPD among children with indirect effects noted among other age groups as well. However, thanks to a strict surveillance network, an increase in non-vaccine serotypes (NVTs causing IPD was noted worldwide and in late 2000s a new second generation vaccine (13-valent pneumococcal conjugate vaccine-PCV13 with an expanded serotype coverage was licensed. Due to the lack of solid effectiveness data, up to know it is difficult to predict how the composition of NVTs will change after the large-scale introduction of PCV13 or whether the characteristics of the serotypes will change. Long-term surveillance of both IPD, pneumonia, acute otitis media and carriage will be crucial to ascertain whether these second generation vaccines are having the desired effect of reducing the incidence of diseases in the long term. Proceedings of the 9th International Workshop on Neonatology · Cagliari (Italy · October 23rd-26th, 2013 · Learned lessons, changing practice and cutting-edge research
Barington, T; Gyhrs, A; Kristensen, Kim
hundred forty-four infants were vaccinated with HibCP-TT at 5 and 6 months. They were randomized into three groups that received TT as part of a diphtheria-tetanus-polio vaccine at either 6 and 7 months (group A), 5 and 6 months (group B), or 4 and 5 months (group C). Maternally acquired TT antibodies...
Dagna O. Constenla
Full Text Available OBJECTIVES: To evaluate the economic impact of vaccination with the pneumococcal 7-valent conjugate vaccine (PCV7 in Brazil, Chile, and Uruguay. METHODS: A decision analytic model was constructed to compare pneumococcal vaccination of children 0-5 years old with no vaccination in Brazil, Chile, and Uruguay. Costs and health outcomes were analyzed from the societal perspective. Vaccine, demographic, epidemiologic, and cost data were incorporated into this economic analysis. RESULTS: At the rate of diphtheria-tetanus-pertussis (DTP vaccine coverage and a vaccine price of US$ 53 per dose, PCV7 was projected to prevent 23 474 deaths per year in children under 5 years old in the three countries studied, thus averting 884 841 disability-adjusted life years (DALYs yearly. To vaccinate the entire birth cohort of the three countries, total vaccine costs would be US$ 613.9 million. At US$ 53 per dose, the cost per DALY averted from a societal perspective would range from US$ 664 (Brazil to US$ 2 019 (Chile. At a cost of US$ 10 per dose, vaccine cost is lower than the overall cost of illness averted (US$ 125 050 497 versus US$ 153 965 333, making it cost effective and cost-saving. CONCLUSIONS: The results of this study demonstrate that the incorporation of PCV7 vaccine at US$ 53 per dose confers health benefits at extra costs. It is unclear whether vaccination at the current price is affordable to these countries.OBJETIVOS: Evaluar el impacto económico de la aplicación de la vacuna antineumocócica conjugada heptavalente (PCV7 en Brasil, Chile y Uruguay. MÉTODOS: Se elaboró un modelo analítico de decisiones para comparar la vacunación antineumocócica de los niños de 0-5 años de edad con la no vacunación, en Brasil, Chile y Uruguay. Los costos y los desenlaces para la salud se analizaron desde el punto de vista de la sociedad. Al análisis económico se incorporaron los costos y los datos demográficos, epidemiológicos y de la vacuna. RESULTADOS
Farzam, Nahid; Ramon-Saraf, Reut; Banet-Levi, Yonit; Lerner-Geva, Liat; Ashkenazi, Shai; Kubler-Kielb, Joanna; Vinogradov, Evgeny; Robbins, John B; Schneerson, Rachel
Shigella flexneri (S. flexneri) 6 has emerged as an important cause of shigellosis. Our efficacy study of Shigella sonnei and S. flexneri 2a O-specific polysaccharide (O-SP) conjugates in 1-4year-olds had too few S. flexneri 2a cases for efficacy evaluation but surprisingly showed protection of 3-4year-olds, S. flexneri 2a-recipients, from S. flexneri 6 infection. To investigate this cross-protection antibodies to both Shigella types were investigated in all sera remaining from previous studies. Twenty to 30% of 3-44year-old humans injected with S. flexneri 2a conjugate responded with ≥4-fold increases of IgG anti type 6, p<0.00001. The specificity of these antibodies was shown by inhibition studies. S. flexneri 6 infection of 2 children induced besides S. flexneri 6, also S. flexneri 2a antibodies, at levels of S. flexneri 2a vaccinees. S. flexneri 2a antibodies induced by S. flexneri 6 conjugates could not be studied since no such conjugate was assessed in humans and mice responded almost exclusively to the O-SP of the injected conjugate, with no cross-reactive antibodies. Our results indicate induction of cross-reactive protective antibodies. The O-acetylated disaccharide shared by S. flexneri 6 and 2a O-SPs, is the likely basis for their cross-reactivity. S. flexneri 6 O-SP conjugates, alone and in combination with S. flexneri 2a, merit further investigation for broad S. flexneri protection. Published by Elsevier Ltd.
Jun, L; Yuguo, C; Zhiguo, W; Jinfeng, L; Huawei, M; Xiuhua, L; Yonggui, Z; Yanhua, X; Kong, Y; Hongtao, L; Yuliang, Z
Invasive meningitis and pneumonia caused by Haemophilus influenzae type b (Hib) is an important cause of childhood mortality in countries where Hib vaccination is not routine. We evaluated the non-inferiority of a licensed Hib vaccine, PRP-CRM(197) compared with a second licensed Hib vaccine, PRP-T, following the recommended Chinese immunisation schedule for infants between 6 months and 1 year of age. In the first study phase, 6-12 month-old infants received two primary doses of either PRP-CRM(197) (n = 335) or PRP-T (n = 335) vaccine administered 1 month apart. In the second study phase 8 months later, the same children received a single booster dose of vaccine identical to that use for priming (PRP-CRM(197), n = 327; PRP-T, n = 333). Serum levels of anti-polyribosylribitol phosphate (PRP) antibodies were measured using enzyme-linked immunosorbent assay (ELISA). Non-inferiority of primary and booster doses was assessed in terms of percentages of subjects with anti-PRP antibody levels associated with providing short-term (≥ 0.15 μg/ml) and long-term (≥ 1.0 μg/ml) protection; the non-inferiority margin was set at -5%. PRP-CRM(197) was demonstrated to be non-inferior to PRP-T. Anti-PRP antibodies levels ≥ 0.15 μg/ml and ≥ 1.0 μg/ml were achieved by 97% of infants in the PRP-CRM(197) group and 98% of infants in the PRP-T group 1 month after primary immunisation, and by all subjects (100%) in both vaccine groups 1 month after booster administration. Safety profiles for both vaccines were similar; no serious adverse events, deaths or adverse events leading to withdrawal occurred during the study. PRP-CRM(197) was well-tolerated and immunologically non-inferior to a licensed comparator Hib vaccine in Chinese infants (Clinicaltrials.gov: NCT01044316 & NCT01226953). © 2013 John Wiley & Sons Ltd.
Efficacy of 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine against acute otitis media and nasopharyngeal carriage in Panamanian children – A randomized controlled trial
Sáez-Llorens, Xavier; Rowley, Stella; Wong, Digna; Rodríguez, Mirna; Calvo, Arlene; Troitiño, Marisol; Salas, Albino; Vega, Vielka; Castrejón, Maria Mercedes; Lommel, Patricia; Pascal, Thierry G.; Hausdorff, William P.; Borys, Dorota; Ruiz-Guiñazú, Javier; Ortega-Barría, Eduardo; Yarzabal, Juan Pablo; Schuerman, Lode
ABSTRACT We previously reported 10-valent pneumococcal non-typeable Haemophilus influenzae (NTHi) protein D conjugate vaccine (PHiD-CV) efficacy in a double-blind randomized trial (ClinicalTrials.gov: NCT00466947) against various diseases, including acute otitis media (AOM). Here, we provide further analyses. In the Panamanian subset, 7,359 children were randomized (1:1) to receive PHiD-CV or control vaccine at age 2/4/6 and 15–18 months. Of these, 2,000 had nasopharyngeal swabs collected. AOM cases were captured when parents sought medical attention for children with AOM symptoms; surveillance was enhanced approximately 2 y into the study through regular telephone calls or home visits by study personnel, who advised parents to visit the clinic if their child had AOM symptoms. Mean follow-up was 31.4 months. Clinical AOM (C-AOM) cases were assessed by physicians and confirmed by otorhinolaryngologists. Middle ear fluid samples, taken from children with C-AOM after specific informed consent, and nasopharyngeal samples were cultured for pathogen identification. For 7,359 children, 2,574 suspected AOM cases were assessed by a primary healthcare physician; 649 cases were C-AOM cases as per protocol definition. From the 503 MEF samples collected, 158 resulted in a positive culture. In the intent-to-treat cohort (7,214 children), PHiD-CV showed VE against first C-AOM (24.0% [95% CI: 8.7, 36.7]) and bacterial (B-AOM) episodes (48.0% [20.3, 66.1]) in children children younger than 24 months, and reduced vaccine-serotype NPC. PMID:28368738
Date, Kashmira A; Bentsi-Enchill, Adwoa; Marks, Florian; Fox, Kimberley
Typhoid vaccination is an important component of typhoid fever prevention and control, and is recommended for public health programmatic use in both endemic and outbreak settings. We reviewed experiences with various vaccination strategies using the currently available typhoid vaccines (injectable Vi polysaccharide vaccine [ViPS], oral Ty21a vaccine, and injectable typhoid conjugate vaccine [TCV]). We assessed the rationale, acceptability, effectiveness, impact and implementation lessons of these strategies to inform effective typhoid vaccination strategies for the future. Vaccination strategies were categorized by vaccine disease control strategy (preemptive use for endemic disease or to prevent an outbreak, and reactive use for outbreak control) and vaccine delivery strategy (community-based routine, community-based campaign and school-based). Almost all public health typhoid vaccination programs used ViPS vaccine and have been in countries of Asia, with one example in the Pacific and one experience using the Ty21a vaccine in South America. All vaccination strategies were found to be acceptable, feasible and effective in the settings evaluated; evidence of impact, where available, was strongest in endemic settings and in the short- to medium-term. Vaccination was cost-effective in high-incidence but not low-incidence settings. Experience in disaster and outbreak settings remains limited. TCVs have recently become available and none are WHO-prequalified yet; no program experience with TCVs was found in published literature. Despite the demonstrated success of several typhoid vaccination strategies, typhoid vaccines remain underused. Implementation lessons should be applied to design optimal vaccination strategies using TCVs which have several anticipated advantages, such as potential for use in infant immunization programs and longer duration of protection, over the ViPS and Ty21a vaccines for typhoid prevention and control. Copyright © 2015. Published by
Mukherjee, Nimisha G; Le Doux, Joseph M; Andrew Lyon, L
Methods are needed to manipulate natural nanoparticles. Viruses are particularly interesting because they can act as therapeutic cellular delivery agents. Here we examine a new method for rapidly modifying retroviruses that uses lipid conjugates composed of a lipid anchor (1,2-distearoyl-sn-glycero-3-phosphoethanolamine), a polyethylene glycol chain, and biotin. The conjugates rapidly and stably modified retroviruses and enabled them to bind streptavidin. The implication of this work for modifying viruses for gene therapy and vaccination protocols is discussed.
Ladhani, Shamez N; Ramsay, Mary; Borrow, Ray; Riordan, Andrew; Watson, John M; Pollard, Andrew J
In 2015, the UK became the first country in the world to have a comprehensive routine meningococcal vaccine programme targeting all of the main capsular groups of N. meningitidis. 1 An infant vaccine programme against meningococcal capsular group B Neisseria meningitidis (MenB) was launched from 1st September with an aim to reduce endemic MenB disease in early childhood. On 1st August 2015, an adolescent programme against groups A, C, W and Y meningococci (MenACWY) was rolled out to halt a growing outbreak of capsular group W disease (MenW) caused by a hypervirulent clone of N. meningitidis, in addition to maintaining control against MenC disease provided by the current adolescent programme. 2. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
Pneumococcal Vaccination Recommendations for Children 1 and Adults by Age and/or Risk Factor Routine Recommendations for Pneumococcal Conjugate Vaccine (PCV13) and Pneumococcal Polysaccharide Vaccine (PPSV23) For children Administer PCV13 ...
Heath, Paul T; Feldman, Robert G
Streptococcus agalactiae (Group B streptococcus) is an important cause of disease in infants, pregnant women, the elderly and in immunosuppressed adults. An effective vaccine is likely to prevent the majority of infant disease (both early and late onset), as well as Group B streptococcus-related stillbirths and prematurity, to avoid the current real and theoretical limitations of intrapartum antibiotic prophylaxis, and to be cost effective. The optimal time to administer such a vaccine would be in the third trimester of pregnancy. The main limitations on the production of a Group B streptococcus vaccine are not technical or scientific, but regulatory and legal. A number of candidates including capsular conjugate vaccines using traditional carrier proteins such as tetanus toxoid and mutant diphtheria toxin CRM197, as well as Group B streptococcus-specific proteins such as C5a peptidase, protein vaccines using one or more Group B streptococcus surface proteins and mucosal vaccines, have the potential to be successful vaccines. The capsular conjugate vaccines using tetanus and CRM197 carrier proteins are the most advanced candidates, having already completed Phase II human studies including use in the target population of pregnant women (tetanus toxoid conjugate), however, no definitive protein conjugates have yet been trialed. However, unless the regulatory environment is changed specifically to allow the development of a Group B streptococcus vaccine, it is unlikely that one will ever reach the market.
Safety, tolerability, and immunogenicity of 7-valent pneumococcal conjugate vaccine in older infants and young children in China who are naive to pneumococcal vaccination: Results of a phase 4 open-label trial.
Li, Rongcheng; Huang, Lirong; Mo, Shunping; Li, Junchun; Zhou, Xin; Chen, Zhangjing; Liang, John; Young, Mariano; Giardina, Peter C; Scott, Daniel A
This postlicensure study was conducted to assess immunogenicity and safety of PCV7 catch-up regimens in previously unvaccinated older infants and young children in China. Healthy children 121 days to vaccination and 1 and 12 months postvaccination. The incidence of clinically important adverse events (AEs) and serious AEs (SAEs), AEs leading to study withdrawal, and protocol-related AEs were assessed throughout the study. Prevaccination serotype-specific GMCs were generally low in subjects children 24 to 90% of subjects had IgG≥0.35 μg/mL for each PCV serotype. At 12-month follow-up, IgG GMCs ranged from 0.65 to 5.19, and all remained above prevaccination IgG GMC; >70% of subjects had IgG≥0.35 μg/mL. Older children generally had the most robust immune response both at 1 month postvaccination and during 12-month follow-up. PCV7 was well tolerated. Pyrexia, which was mild to moderate in severity, was the most common AE. Two subjects reported SAEs (n=4), and there was 1 study withdrawal; none of these were considered treatment related. In China, PCV7 catch-up vaccinations given to older infants and young children naive to pneumococcal vaccines resulted in a robust immune response to all serotypes; this response persisted after 1 year. PCV7 was well tolerated in Chinese infants and children. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.
A method for the synthesis of dendrimer conjugates having a well-defined chemical structure, comprising one or more carbohydrate moieties and one or more immunomodulating substances coupled to a dendrimer, is presented. First, the carbohydrate is bound to the dendrimer in a chemoselective manner...... conjugates and their use in vaccination, production of antibodies, high throughput screening, diagnostic assays and libraries....
Cremers, Amelieke J H; Mobegi, Fredrick M; de Jonge, Marien I; van Hijum, Sacha A F T; Meis, Jacques F; Hermans, Peter W M; Ferwerda, Gerben; Bentley, Stephen D; Zomer, Aldert L
The 7-valent pneumococcal conjugated vaccine (PCV7) has affected the genetic population of Streptococcus pneumoniae in pediatric carriage. Little is known however about pneumococcal population genomics in adult invasive pneumococcal disease (IPD) under vaccine pressure. We sequenced and serotyped
Lee, Hoan Jong; Choe, Young June; Hong, Young-Jin; Kim, Kyung-Hyo; Park, Su Eun; Kim, Yun-Kyung; Oh, Chi-Eun; Lee, Hyunju; Song, Hyoyoung; Bock, Hans; Casula, Daniela; Bhusal, Chiranjiwi; Arora, Ashwani Kumar
Neisseria meningitidis serogroup B is a significant cause of septicaemia and meningitis worldwide. This phase 3 randomised, controlled study assessed the immunogenicity and safety of a multicomponent meningococcal serogroup B vaccine, 4CMenB, in healthy Korean adolescents. 264 adolescents (11-17 years old) were randomised to receive two doses, one month apart, of 4CMenB or control vaccines [placebo followed by one dose of a quadrivalent meningococcal ACWY glycoconjugate vaccine (MenACWY-CRM)]. Immunogenicity was evaluated by serum bactericidal assay with human complement (hSBA) against three serogroup B test strains specific for individual vaccine antigens (fHbp, NadA or PorA P1.4), and by enzyme-linked immunosorbent assay (ELISA) against the NHBA antigen. Solicited reactions and adverse events (AEs) were assessed. One month post-second vaccination, 98%, 97%, and 97% of subjects in the 4CMenB group achieved hSBA titres ≥ 4 against the fHbp, NadA and PorA test strains, respectively, while percentages in the Control group were comparable to baseline (27%, 16%, and 17%, respectively). Geometric mean ELISA concentrations (GMCs) against NHBA increased 52-fold relative to baseline in the 4CMenB group, while there was no substantial increase in GMCs in the Control group (1.05-fold). Frequencies of solicited reactions after any vaccination were higher in the 4CMenB group than in the Control group, although most reactions were of short duration and mild to moderate intensity. There were no vaccine-related serious AEs. Two doses of 4CMenB induced robust immune responses against the vaccine antigens and were well tolerated, with no safety concerns identified, in Korean adolescents (NCT01973218). Copyright © 2016 Elsevier Ltd. All rights reserved.
MuŽíková, G; Laga, R
Vaccines have helped considerably in eliminating some life-threatening infectious diseases in past two hundred years. Recently, human medicine has focused on vaccination against some of the world's most common infectious diseases (AIDS, malaria, tuberculosis, etc.), and vaccination is also gaining popularity in the treatment of cancer or autoimmune diseases. The major limitation of current vaccines lies in their poor ability to generate a sufficient level of protective antibodies and T cell responses against diseases such as HIV, malaria, tuberculosis and cancers. Among the promising vaccination systems that could improve the potency of weakly immunogenic vaccines belong macromolecular carriers (water soluble polymers, polymer particels, micelles, gels etc.) conjugated with antigens and immunistumulatory molecules. The size, architecture, and the composition of the high molecular-weight carrier can significantly improve the vaccine efficiency. This review includes the most recently developed (bio)polymer-based vaccines reported in the literature.
Sónia T Almeida
Full Text Available Among the over 90 serotypes of Streptococcus pneumoniae described, serotypes 1, 5, and 7F account for a significant proportion of invasive disease worldwide and are now covered by the most recent 10- and 13-valent pneumococcal conjugate vaccines (PCVs. The epidemiology of these serotypes in carriage remains poorly studied because they are rarely detected. We aimed to gain insights into the epidemiology and population structure of serotypes 1, 5 and 7F carried by children in Portugal before PCV10 and PCV13 became widely used. Isolates obtained in cross-sectional studies carried out over a 15-year period (1996-2010 were retrospectively pooled and characterized. Of 5,123 pneumococci obtained, 70 were associated with serotypes 1 (n = 21, 5 (n = 7, and 7F (n = 42. The highest prevalence detected was 3.3% for serotype 1 in 2006, 1% for serotype 5 in 2009, and 3.3% for serotype 7F in 2006; Serotype 1 was associated with PMEN international clones Sweden(1-28(ST306 and Sweden(1-40(ST304; serotype 5 was associated with Colombia(5-19(ST289; and serotype 7F was associated with Netherlands(7F-39(ST191. All these isolates were fully susceptible. Most carriers of serotypes 1 (86%, 5 (86%, and 7F (91% were older than two years but a significant association with older age was only observed for serotype 7F (p = 0.006. Evidence for cross-transmission was obtained. In conclusion, we were able to detect and characterize the rarely carried serotypes 1, 5, and 7F among healthy children in Portugal. These data will constitute an important baseline for upcoming surveillance studies aimed to establish the impact of novel PCVs targeting these serotypes in carriage.
Encapsulation of an EP67-Conjugated CTL Peptide Vaccine in Nanoscale Biodegradable Particles Increases the Efficacy of Respiratory Immunization and Affects the Magnitude and Memory Subsets of Vaccine-Generated Mucosal and Systemic CD8+ T Cells in a Diameter-Dependent Manner.
Karuturi, Bala V K; Tallapaka, Shailendra B; Yeapuri, Pravin; Curran, Stephen M; Sanderson, Sam D; Vetro, Joseph A
The diameter of biodegradable particles used to coencapsulate immunostimulants and subunit vaccines affects the magnitude of memory CD8 + T cells generated by systemic immunization. Possible effects on the magnitude of CD8 + T cells generated by mucosal immunization or memory subsets that potentially correlate more strongly with protection against certain pathogens, however, are unknown. In this study, we conjugated our novel host-derived mucosal immunostimulant, EP67, to the protective MCMV CTL epitope, pp89, through a lysosomal protease-labile double arginine linker (pp89-RR-EP67) and encapsulated in PLGA 50:50 micro- or nanoparticles. We then compared total magnitude, effector/central memory (CD127/KRLG1/CD62L), and IFN-γ/TNF-α/IL-2 secreting subsets of pp89-specific CD8 + T cells as well as protection of naive female BALB/c mice against primary respiratory infection with MCMV 21 days after respiratory immunization. We found that decreasing the diameter of encapsulating particle from ∼5.4 μm to ∼350 nm (i) increased the magnitude of pp89-specific CD8 + T cells in the lungs and spleen; (ii) partially changed CD127/KLRG1 effector memory subsets in the lungs but not the spleen; (iii) changed CD127/KRLG1/CD62L effector/central memory subsets in the spleen; (iv) changed pp89-responsive IFN-γ/TNF-α/IL-2 secreting subsets in the lungs and spleen; (v) did not affect the extent to which encapsulation increased efficacy against primary MCMV respiratory infection over unencapsulated pp89-RR-EP67. Thus, although not observed under our current experimental conditions with MCMV, varying the diameter of nanoscale biodegradable particles may increase the efficacy of mucosal immunization with coencapsulated immunostimulant/subunit vaccines against certain pathogens by selectively increasing memory subset(s) of CD8 + T cells that correlate the strongest with protection.
The safety and immunogenicity of TETRActHIB (a vaccine combining diphtheria and tetanus toxoids-pertussis vaccine (DTP) with Haemophilus influenzae type b (Hib) conjugate vaccine (polyribosyl ribitol phosphate conjugated to tetanus protein) (PRP-T)) was assessed in 131 Cape Town infants immunised at 6, 10 and 14 ...
Pagliusi, Sonia; Jain, Rishabh; Suri, Rajinder Kumar
The Developing Countries Vaccine Manufacturers' Network (DCVMN) held its fifteenth annual meeting from October 27-29, 2014, New Delhi, India. The DCVMN, together with the co-organizing institution Panacea Biotec, welcomed over 240 delegates representing high-profile governmental and nongovernmental global health organizations from 36 countries. Over the three-day meeting, attendees exchanged information about their efforts to achieve their shared goal of preventing death and disability from known and emerging infectious diseases. Special praise was extended to all stakeholders involved in the success of polio eradication in South East Asia and highlighted challenges in vaccine supply for measles-rubella immunization over the coming decades. Innovative vaccines and vaccine delivery technologies indicated creative solutions for achieving global immunization goals. Discussions were focused on three major themes including regulatory challenges for developing countries that may be overcome with better communication; global collaborations and partnerships for leveraging investments and enable uninterrupted supply of affordable and suitable vaccines; and leading innovation in vaccines difficult to develop, such as dengue, Chikungunya, typhoid-conjugated and EV71, and needle-free technologies that may speed up vaccine delivery. Moving further into the Decade of Vaccines, participants renewed their commitment to shared responsibility toward a world free of vaccine-preventable diseases. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.
Clostridium difficile Recombinant Toxin A Repeating Units as a Carrier Protein for Conjugate Vaccines: Studies of Pneumococcal Type 14, Escherichia coli K1, and Shigella flexneri Type 2a Polysaccharides in Mice
Pavliakova, Danka; Moncrief, J. Scott; Lyerly, David M.; Schiffman, Gerald; Bryla, Dolores A.; Robbins, John B.; Schneerson, Rachel
Unlike the native protein, a nontoxic peptide (repeating unit of the native toxin designated rARU) from Clostridium difficile toxin A (CDTA) afforded an antigen that could be bound covalently to the surface polysaccharides of pneumococcus type 14, Shigella flexneri type 2a, and Escherichia coli K1. The yields of these polysaccharide-protein conjugates were significantly increased by prior treatment of rARU with succinic anhydride. Conjugates, prepared with rARU or succinylated (rARUsucc), were administered to mice by a clinically relevant dosage and immunization scheme. All conjugates elicited high levels of serum immunoglobulin G both to the polysaccharides and to CDTA. Conjugate-induced anti-CDTA had neutralizing activity in vitro and protected mice challenged with CDTA, similar to the rARU alone. Conjugates prepared with succinylated rARU, therefore, have potential for serving both as effective carrier proteins for polysaccharides and for preventing enteric disease caused by C. difficile. PMID:10722615
Josefsberg, Jessica O; Buckland, Barry
The evolution of vaccines (e.g., live attenuated, recombinant) and vaccine production methods (e.g., in ovo, cell culture) are intimately tied to each other. As vaccine technology has advanced, the methods to produce the vaccine have advanced and new vaccine opportunities have been created. These technologies will continue to evolve as we strive for safer and more immunogenic vaccines and as our understanding of biology improves. The evolution of vaccine process technology has occurred in parallel to the remarkable growth in the development of therapeutic proteins as products; therefore, recent vaccine innovations can leverage the progress made in the broader biotechnology industry. Numerous important legacy vaccines are still in use today despite their traditional manufacturing processes, with further development focusing on improving stability (e.g., novel excipients) and updating formulation (e.g., combination vaccines) and delivery methods (e.g., skin patches). Modern vaccine development is currently exploiting a wide array of novel technologies to create safer and more efficacious vaccines including: viral vectors produced in animal cells, virus-like particles produced in yeast or insect cells, polysaccharide conjugation to carrier proteins, DNA plasmids produced in E. coli, and therapeutic cancer vaccines created by in vitro activation of patient leukocytes. Purification advances (e.g., membrane adsorption, precipitation) are increasing efficiency, while innovative analytical methods (e.g., microsphere-based multiplex assays, RNA microarrays) are improving process understanding. Novel adjuvants such as monophosphoryl lipid A, which acts on antigen presenting cell toll-like receptors, are expanding the previously conservative list of widely accepted vaccine adjuvants. As in other areas of biotechnology, process characterization by sophisticated analysis is critical not only to improve yields, but also to determine the final product quality. From a regulatory
Jansen, Angelique G S C; Hak, Eelko; Veenhoven, Reinier H; Damoiseaux, Roger A M J; Schilder, Anne G M; Sanders, Elisabeth A M
BACKGROUND: Acute otitis media (AOM) is a very common early infancy and childhood disease. The marginal benefits of antibiotics on AOM, the increasing problem of bacterial resistance to antibiotics, and the huge estimated direct and indirect annual costs associated with otitis media (OM) have
Fortanier, Alexandre C.; Venekamp, Roderick P.; Boonacker, Chantal W. B.; Hak, Eelko; Schilder, Anne G. M.; Sanders, Elisabeth A. M.; Damoiseaux, Roger A. M. J.
BACKGROUND: Acute otitis media (AOM) is a very common respiratory infection in early infancy and childhood. The marginal benefits of antibiotics for AOM in low-risk populations in general, the increasing problem of bacterial resistance to antibiotics and the huge estimated direct and indirect annual
Micoli, Francesca; Rondini, Simona; Gavini, Massimiliano; Lanzilao, Luisa; Medaglini, Donata; Saul, Allan; Martin, Laura B
Enteric fevers remain a common and serious disease, affecting mainly children and adolescents in developing countries. Salmonella enterica serovar Typhi was believed to cause most enteric fever episodes, but several recent reports have shown an increasing incidence of S. Paratyphi A, encouraging the development of a bivalent vaccine to protect against both serovars, especially considering that at present there is no vaccine against S. Paratyphi A. The O-specific polysaccharide (O:2) of S. Paratyphi A is a protective antigen and clinical data have previously demonstrated the potential of using O:2 conjugate vaccines. Here we describe a new conjugation chemistry to link O:2 and the carrier protein CRM(197), using the terminus 3-deoxy-D-manno-octulosonic acid (KDO), thus leaving the O:2 chain unmodified. The new conjugates were tested in mice and compared with other O:2-antigen conjugates, synthesized adopting previously described methods that use CRM(197) as carrier protein. The newly developed conjugation chemistry yielded immunogenic conjugates with strong serum bactericidal activity against S. Paratyphi A.
Full Text Available Enteric fevers remain a common and serious disease, affecting mainly children and adolescents in developing countries. Salmonella enterica serovar Typhi was believed to cause most enteric fever episodes, but several recent reports have shown an increasing incidence of S. Paratyphi A, encouraging the development of a bivalent vaccine to protect against both serovars, especially considering that at present there is no vaccine against S. Paratyphi A. The O-specific polysaccharide (O:2 of S. Paratyphi A is a protective antigen and clinical data have previously demonstrated the potential of using O:2 conjugate vaccines. Here we describe a new conjugation chemistry to link O:2 and the carrier protein CRM(197, using the terminus 3-deoxy-D-manno-octulosonic acid (KDO, thus leaving the O:2 chain unmodified. The new conjugates were tested in mice and compared with other O:2-antigen conjugates, synthesized adopting previously described methods that use CRM(197 as carrier protein. The newly developed conjugation chemistry yielded immunogenic conjugates with strong serum bactericidal activity against S. Paratyphi A.
Heegaard, Peter M. H.; Boas, Ulrik; Sørensen, Nanna Skall
for efficient immunostimulating compounds (adjuvants) that can increase the efficiency of vaccines, as dendrimers can provide molecularly defined multivalent scaffolds to produce highly defined conjugates with small molecule immunostimulators and/or antigens. The review gives an overview on the use...... of dendrimers as molecularly defined carriers/presenters of small antigens, including constructs that have built-in immunostimulatory (adjuvant) properties, and as stand-alone adjuvants that can be mixed with antigens to provide efficient vaccine formulations. These approaches allow the preparation...... of molecularly defined vaccines with highly predictable and specific properties and enable knowledge-based vaccine design substituting the traditional empirically based approaches for vaccine development and production....
[Incidence of admissions due to pneumonia in children under 24 months old before and after the introduction of the 10-valent pneumococcal conjugate vaccine into the National Immunization Program of Chile].
Fernández V, José Pablo; Goecke H, Carola; von Borries, Cecilia; Tapia R, Natalia; Santolaya de P, María Elena
Streptococcus pneumoniae is the leading cause of bacterial pneumonia in children, especially in the hospitalized population. The 10-valent pneumococcal vaccine was included in the National Immunization Program of Chile in 2011. This study aims to evaluate the incidence of pneumonia in hospitalized children<24 months of age in the Luis Calvo Mackenna Hospital before and after the introduction of the pneumococcal vaccine into the National Immunization Program. Passive surveillance study. Patients<24 months with discharge diagnosis of bacterial pneumonia from Luis Calvo Mackenna Hospital were studied between 2009 and 2013. Data were obtained from the Luis Calvo Mackenna Hospital's Statistical Service. The incidence of pneumonia was evaluated in the pre-vaccination period (2009-2010) and in the post-vaccination period (2012-2013). During the study period, an average of 4,321 discharges/year was observed in children<24 months (range: 3,587-4,702), with a significant decrease from pre- to post-vaccination vaccine period (4,644 vs 4,013, P<.001). The average incidence of pneumonia ranged from 3.4/100,000 to 1.5/100,000 in the pre- and post-vaccine period, respectively (P=.009), with an annual mean of 157 cases of pneumonia in the pre- vaccine period, and 62 cases in the postvaccine period (P<.001) and a decrease in incidence between the two periods of 56%. This study confirms information previously obtained in other countries, which show a decrease in the incidence of pneumonia associated with the implementation of a pneumococcal vaccine at the population level. Ongoing surveillance is required to evaluate if this effect is maintained over time and expands to older populations. Copyright © 2015 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.
Comparison of two-dose priming plus 9-month booster with a standard three-dose priming schedule for a ten-valent pneumococcal conjugate vaccine in Nepalese infants: a randomised, controlled, open-label, non-inferiority trial.
Hamaluba, Mainga; Kandasamy, Rama; Upreti, Shyam R; Subedi, Giri R; Shrestha, Shrijana; Bhattarai, Shiva; Gurung, Meeru; Pradhan, Rahul; Voysey, Merryn; Gurung, Santosh; Pradhan, Shachi; Thapa, Anushil K; Maharjan, Rakesh; Kiran, Usha; Kerridge, Simon A; Hinds, Jason; van der Klis, Fiona; Snape, Matthew D; Murdoch, David R; Kelly, Sarah; Kelly, Dominic F; Adhikari, Neelam; Thorson, Stephen; Pollard, Andrew J
Use of pneumococcal conjugate vaccines (PCVs) in resource-poor countries has focused on early infant immunisation with little emphasis on protection in late infancy and beyond. Boosting of the immune response later in infancy might provide improved persistence of immunogenicity into early childhood, however data are scarce. The aim of this study was to investigate if a two-dose prime with booster at age 9 months compared with a three-dose prime-only PCV schedule provided non-inferior immunogenicity in early infancy and superior persistence of antibody responses in early childhood. We did an open-label, randomised, parallel group, controlled trial in healthy infants aged 40-60 days from Kathmandu, Nepal. Participants were randomly allocated (4:4:5 ratio) to receive PCV10 in addition to routine immunisations either as a two-dose prime and boost (2+1), three-dose prime (3+0), or two doses after completion of the initial study phase (0+2). We used a computer generated randomisation list with randomly varying block sizes. We followed up participants at age 2-4 years together with a group of unvaccinated controls. Sera were analysed for opsonophagocytic activity, protein D, and PCV10 serotype-specific IgG. Laboratory staff was masked to intervention group assignment. The primary outcome measure was to determine the proportion of participants in the 2+1 group at age 10 months with specific IgG for serotypes 1, 5, and 14 of at least 0·2 μg/mL in the per-protocol population. The secondary outcomes were non-inferiority (within 10% levels) at age 18 weeks for the proportion of participants in the 2+1 group compared with the 3+0 group with serotypes 1, 5, and 14 specific IgG of at least 0·2 μg/mL; the proportion of participants with PCV10 serotype-specific IgG of at least 0·2 μg/mL and opsonophagocytic activity reciprocal titre of at least 8 at ages 18 weeks and 10 months; and nasopharyngeal pneumococcal serotype-specific carriage rates at age 9 months in each study
叶强; 谢贵林; 李亚南; 赵志强; 李荣成; 何莉; 谭晓梅; 李艳萍; 杜送田; 李凤祥
目的 评价b型流感嗜血杆菌结合疫苗(Hib-TT)安全性和免疫原性.方法 分别采用Hib-TT试验疫苗和对照疫苗3针免疫接种3～5月龄婴幼儿,观察疫苗安全性,并采用定量ELISA法分别测定免疫前、免疫后和加强免疫后血清特异性IgG抗体浓度.结果 实验疫苗和对照疫苗两组间不良反应总发生率(实验疫苗组为23.85％,对照疫苗组为31.40％)差异无统计学意义(x2=0.5,P＞0.05),发热性总不良反应率分别为22.3％和31.3％,中、强发热反应率分别为3.67％和4.48％,差异无统计学意义；实验疫苗受试者局部红、肿、硬结等不良反应率为1.22％.实验疫苗3剂免疫后受试者血清抗Hib PRP IgG抗体平均几何浓度(GMC)为6.6786 μg/ml,对照疫苗组血清抗体GMC为7.5346 μg/ml,两组间抗体GMC差异无统计学意义(x2=0.147,P=0.702)；加强免疫1剂后,实验疫苗组受试者血清抗体GMC从加强免疫前的2.6396 μg/ml上升为6.2044μg/ml.结论 实验疫苗接种3～5月龄婴幼儿具有良好的安全性.用间隔1个月、3剂次接种的基础免疫程序能诱导该年龄组受试者产生长期保护水平的血清特异性抗体,加强免疫1剂后能诱导机体产生免疫记忆反应.%Objectives To evaluate the safety and immunogenicity of Haemophilus influenzae type b capsular-tetanus toxoid(Hib-TT) conjugate vaccine.Methods In an open-controlled,randomized trial,the eligible and consented infants of 3 to 5 months-old received 3 doses of Hib-TT or a licensed Hib-TT conjugate vaccine(Anerbao) as the control vaccine to evaluate safety; The serum anti-Hib PRP IgG antibody mean geometric concentration (GMC) in both groups after primary and boosting vaccination were measured by ELISA.Results No apparent difference in the frequency of total adverse reactions observed between two groups (study vaccine 23.85％ vs.comparator 31.40％) (x2=0.5,P＞0.05).The mild and severe fever reaction of both vaccines was 3.67％ and 4
Tiffay, Kathleen; Jodar, Luis; Kieny, Marie-Paule; Socquet, Muriel; LaForce, F Marc
In 2001, the Meningitis Vaccine Project (MVP) was tasked to develop, test, license, and introduce a group A meningococcal (MenA) conjugate vaccine for sub-Saharan Africa. African public health officials emphasized that a vaccine price of less than US$0.50 per dose was necessary to ensure introduction and sustained use of this new vaccine. Initially, MVP envisioned partnering with a multinational vaccine manufacturer, but the target price and opportunity costs were problematic and formal negotiations ended in 2002. MVP chose to become a "virtual vaccine company," and over the next decade managed a network of public-private and public-public partnerships for pharmaceutical development, clinical development, and regulatory submission. MVP supported the transfer of key know-how for the production of group A polysaccharide and a new conjugation method to the Serum Institute of India, Ltd, based in Pune, India. A robust staff structure supported by technical consultants and overseen by advisory groups in Europe and Africa ensured that the MenA conjugate vaccine would meet all international standards. A robust project structure including a team of technical consultants and 3 advisory groups in Europe and Africa ensured that the MenA conjugate vaccine (PsA-TT, MenAfriVac) was licensed by the Drug Controller General of India and prequalified by the World Health Organization in June 2010. The vaccine was introduced in Burkina Faso, Mali, and Niger in December 2010. The development, through a public-private partnership, of a safe, effective, and affordable vaccine for sub-Saharan Africa, PsA-TT, offers a new paradigm for the development of vaccines specifically targeting populations in resource-poor countries. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.
Two hundreds years after the discovery of the smallpox vaccine, immunization remains one of the most powerful tools of preventive medicine. Immunization was born with Jenner, then Pasteur and expanded during the 19th and 20th century. It started with the empirical observation of cross-immunity between two diseases, cowpox and smallpox. It became a real science, with pathogen isolation, culture and attenuation or inactivation, to prepare a vaccine. Together with clinical and biological efficacy studies and adverse events assessments, it constructed the concept of "vaccinology". Protein conjugation of polyosidic vaccines has made possible early immunisation of infants. Nowadays, recombinant, reassortant, or virus-like particles technologies open the road for new vaccines. Ongoing research opens the way for the development of new vaccines that will help to control transmittable diseases for which we are lacking antimicrobial agents.
Vaccinations; Immunizations; Immunize; Vaccine shots; Prevention - vaccine ... of the vaccine. VACCINE SCHEDULE The recommended vaccination (immunization) schedule is updated every 12 months by the ...
Diana C Otczyk
Full Text Available Pneumonia in childhood is endemic in large parts of the world and in particular, in developing countries, as well as in many indigenous communities within developed nations. Haemophilus influenzae type b and Streptococcus pneumoniae conjugate vaccines are currently available against the leading bacterial causes of pneumonia. The use of the vaccines in both industrialised and developing countries have shown a dramatic reduction in the burden of pneumonia and invasive disease in children. However, the greatest threat facing pneumococcal conjugate vaccine effectiveness is serotype replacement. The current vaccines provide serotype-specific, antibody–mediated protection against only a few of the 90+ capsule serotypes. Therefore, there has been a focus in recent years to rapidly advance technologies that will result in broader disease coverage and more affordable vaccines that can be used in developing countries. The next generation of pneumococcal vaccines have advanced to clinical trials.
In the last decade, meningococcal serogroup C conjugate vaccination programs have been demonstrated to be hugely successful with a truly impressive public health impact. In sub-Saharan Africa, with the implementation of an affordable serogroup A conjugate vaccine, it is hoped that a similar public health impact will be demonstrated. Challenges still remain in the quest to develop and implement broadly protective vaccines against serogroup B disease. New, broad coverage vaccines against serogroup B are for the first time becoming available although little is known about their antibody persistence, effectiveness or effect on nasopharyngeal carriage. Enhanced surveillance following any potential vaccine introduction against serogroup B needs to be thoroughly implemented. The future now holds a distinct possibility, globally, for substantially decreasing meningococcal disease, regardless of infecting serogroup. © 2012 Blackwell Publishing Ltd.
Background: Vaccine antigens targeting specific P. falciparum parasite stages are under pre-clinical and clinical development. It seems plausible that vaccine with multiple specificities will offer higher protection. With this hypothesis, we exploited the Spy- Tag/SpyCatcher conjugation system to make a, post expression, dual ...
Aubert, M; Aumaître, H; Beytout, J; Bloch, K; Bouhour, D; Callamand, P; Chave, C; Cheymol, J; Combadière, B; Dahlab, A; Denis, F; De Pontual, L; Dodet, B; Dommergues, M-A; Dufour, V; Gagneur, A; Gaillat, J; Gaudelus, J; Gavazzi, G; Gillet, Y; Gras-le-Guen, C; Haas, H; Hanslik, T; Hau-Rainsard, I; Larnaudie, S; Launay, O; Lorrot, M; Loulergue, P; Malvy, D; Marchand, S; Picherot, G; Pinquier, D; Pulcini, C; Rabaud, C; Regnier, F; Reinert, P; Sana, C; Savagner, C; Soubeyrand, B; Stephan, J-L; Strady, C
The annual meeting of the Infectious Disease Society of America (IDSA) ; which brought together nearly 5000 participants from over 80 countries in Vancouver, Canada, October 21 to 24, 2010 ; provided a review of the influenza (H1N1) 2009 pandemic, evaluated vaccination programmes and presented new vaccines under development. With 12,500 deaths in the United States in 2009-2010, the influenza (H1N1) 2009 pandemic was actually less deadly than the seasonal flu. But it essentially hit the young, and the toll calculated in years of life lost is high. The monovalent vaccines, whether live attenuated or inactivated with or without adjuvants, were well tolerated in toddlers, children, adults and pregnant women. In order to protect infants against pertussis, family members are urged to get their booster shots. The introduction of the 13-valent Pneumococcal conjugated vaccine in the beginning of 2010 may solve - but for how long ? - the problem of serotype replacement, responsible for the re-increasing incidence of invasive Pneumococcal infections observed in countries that had introduced the 7-valent vaccine. The efficacy of a rotavirus vaccine has been confirmed, with a reduction in hospitalization in the United States and a reduction in gastroenteritis-related deaths in Mexico. In the United States, vaccination of pre-adolescents against human papillomavirus (HPV) has not resulted in any specific undesirable effects. Routine vaccination against chicken pox, recommended since 1995, has not had an impact on the evolution of the incidence of shingles. Vaccination against shingles, recommended in the United States for subjects 60 years and over, shows an effectiveness of 55 %, according to a cohort study (Kaiser Permanente, Southern California). Although some propose the development of personalized vaccines according to individual genetic characteristics, the priority remains with increasing vaccine coverage, not only in infants but also in adults and the elderly. Vaccine
Cost-effectiveness of pneumococcal conjugate vaccination in Latin America and the Caribbean: a regional analysis Rentabilidad médica de la vacunación antineumocócica en América Latina y el Caribe: un análisis regional
Full Text Available OBJECTIVE: In Latin America and the Caribbean, routine vaccination of infants against Streptococcus pneumoniae would need substantial investment by governments and donor organizations. Policymakers need information about the projected health benefits, costs, and cost-effectiveness of vaccination when considering these investments. Our aim was to incorporate vaccine, demographic, epidemiologic, and cost data into an economic analysis of pneumococcal vaccination of infants in Latin America and the Caribbean. METHODS: We previously used a structured literature review to develop regional estimates of the incidence of disease. Cost data were collected from physician interviews and public fee schedules. We then constructed a decision analytic model to compare pneumococcal conjugate vaccination of infants with no vaccination across this region, examining only vaccine's direct effects on children. RESULTS: Pneumococcal vaccination at the rate of diphtheria-tetanus-pertussis vaccine coverage was projected to prevent 9 500 deaths per year in children aged 0 to 5 years in the region, or approximately one life saved per 1 100 infants vaccinated. These saved lives as well as averted cases of deafness, motor deficit, and seizure result in 321 000 disability-adjusted life years (DALYs being averted annually. At vaccine prices between US$5 and US$53 per dose, the cost per DALY averted from a societal perspective would range from US$154 to US$5 252. CONCLUSION: Pneumococcal conjugate vaccine was highly cost-effective up to $40 per dose. Introduction of pneumococcal vaccine in the Latin American and Caribbean region is projected to reduce childhood mortality and to be highly cost-effective across a range of possible costs.OBJETIVO: En América Latina y el Caribe, la vacunación sistemática de niños contra Streptococcus pneumoniae podría requerir inversiones considerables de los gobiernos y organizaciones donantes. Al evaluar estas inversiones se requiere
Fisher, Robert A
This book appears at a time of intense activity in optical phase conjugation. We chose not to await the maturation of the field, but instead to provide this material in time to be useful in its development. We have tried very hard to elucidate and interrelate the various nonlinear phenomena which can be used for optical phase conjugation.
Haemophilus influenzae type b (Hib) conjugate vaccine is a safe and effective vaccine that can prevent meningitis and pneumonia caused by Hib disease. Hib vaccine is recommended for all children under 5 years. Despite the availability of safe and effective Hib vaccines since early 1987, Gambia was
The first dose of a Haemophilus influenzae type b conjugate vaccine reactivates memory B cells: evidence for extensive clonal selection, intraclonal affinity maturation, and multiple isotype switches to IgA2
Hougs, L; Juul, L; Ditzel, H J
selected, and expanded population of cells existing before vaccination, i.e., memory B cells. The dominating heavy and light chains of the response were combined in a Fab that bound HibCP. It was shown that the shared heavy and light chain mutations increased the affinity for HibCP considerably, indicating...
of development. Food vaccines may also help to suppress autoimmunity disorders such as Type-1. Diabetes. Key words: Edible vaccines, oral vaccines, antigen expression, food vaccines. INTRODUCTION. Vaccination involves the stimulation of the immune system to prepare it for the event of an invasion from a particular ...
... During Pregnancy Frequently Asked Questions about Vaccine Recalls Historical Vaccine Safety Concerns FAQs about GBS and Menactra ... CISA Resources for Healthcare Professionals Evaluation Current Studies Historical Background 2001-12 Publications Technical Reports Vaccine Safety ...
Matondo, Sungwa; Thrane, Susan; Janitzek, Christoph Mikkel
Catcher peptide. The covalent interaction between SpyTag/SpyCatcher enables the formation of DBL1x-DBL2x-ID2a:CSP conjugate vaccine. Immunogenicity and quality of antibody responses induced by the conjugate vaccine, as well as a control CSP-SpyCatcher vaccine, was tested in BALB/c mice. Results: Serum samples...... obtained from mice immunized with the conjugate vaccine were able to recognize both untagged DBL1x-DBL2x-ID2a as well as CSP antigen. Moreover, the geometric mean anti-CSP antibody titer was 1.9-fold higher in serum (at day 35 and 55 post-first immunization) from mice immunized with the conjugate vaccine......, as compared to mice receiving the control vaccine. Conclusion: The data obtained in this study serves as proof-of-concept for the simultaneous induction of antibodies directed against individual antigen components in a dual stage anti-malaria vaccine....
Full Text Available Apesar da ampla utilização do conceito de qualidade conjugal, identifica-se falta de clareza conceitual acerca das variáveis que o compõem. Esse artigo apresenta revisão da literatura na área com o objetivo de mapear o conceito de qualidade conjugal. Foram analisadas sete principais teorias sobre o tema: Troca Social, Comportamental, Apego, Teoria da Crise, Interacionismo Simbólico. Pelos postulados propostos nas diferentes teorias, podem-se identificar três grupos de variáveis fundamentais na definição da qualidade conjugal: recursos pessoais dos cônjuges, contexto de inserção do casal e processos adaptativos. Neste sentido, a qualidade conjugal é resultado do processo dinâmico e interativo do casal, razão deste caráter multidimensional.
... version Home Brain, Spinal Cord, and Nerve Disorders Cranial Nerve Disorders Conjugate Gaze Palsies Horizontal gaze palsy Vertical ... Version. DOCTORS: Click here for the Professional Version Cranial Nerve Disorders Overview of the Cranial Nerves Internuclear Ophthalmoplegia ...
Paraschuk, Dmitry Y
This report results from a contract tasking Moscow State University as follows: Conjugated polymers are promising materials for many photonics applications, in particular, for photovoltaic and solar cell devices...
Full Text Available Polyethylene glycol (PEG at the moment is considered the leading polymer for protein conjugation in view of its unique properties, as well as to its low toxicity in humans, qualities which have been confirmed by its extensive use in clinical practice. Other polymers that are safe, biodegradable and custom-designed have, nevertheless, also been investigated as potential candidates for protein conjugation. This review will focus on natural polymers and synthetic linear polymers that have been used for protein delivery and the results associated with their use. Genetic fusion approaches for the preparation of protein-polypeptide conjugates will be also reviewed and compared with the best known chemical conjugation ones.
Roberts, James R; Thompson, David; Rogacki, Brianna; Hale, Jessica J; Jacobson, Robert M; Opel, Douglas J; Darden, Paul M
Addressing parental vaccine hesitancy may increase adolescent vaccination acceptance. However, no validated measure exists to identify parents hesitant toward adolescent vaccines. To determine if a modified version of the Parent Attitudes about Childhood Vaccines (PACV) survey, a previously validated tool to identify parental hesitancy toward vaccines in infants, predicts adolescent vaccine uptake at office visits. We modified the PACV for use in the adolescent setting and distributed it to a convenience sample of parents of adolescents aged 11 to 17 presenting for care at a diverse group of six pediatric practices in Oklahoma and South Carolina. We determined the vaccination status of the parents' adolescents for 3 vaccines (Tetanus-diphtheria-acellular pertussis [Tdap], meningococcal conjugate [MCV4], and human papillomavirus [HPV] vaccines). We used Fisher's exact tests to compare vaccination status with each survey item and with an overall general hesitancy scale that we constructed. We analyzed 363 surveys. At the time of the visit, vaccination coverage was 84% for Tdap, 73% for MCV, and 45% for any dose of HPV. Thirty-nine percent of parents expressed concern about vaccine efficacy and 41% expressed concern about side effects. Forty-five percent of parents disagreed with the statement that "teens can get all of the vaccines that are due at a single visit." Two individual items were associated with not receiving a dose of HPV vaccine that was due. The overall modified PACV score failed to predict adolescent vaccine uptake at an office visit. Several individual items were associated with vaccine uptake. The cumulative modified PACV, a general measure of vaccine hesitancy, was not associated with vaccination status despite illuminating parental hesitancy. We need to better understand vaccine-specific concerns for the adolescent population. Copyright © 2015 Elsevier Ltd. All rights reserved.
... Vaccine Safety Vaccines Work Vaccine Types Vaccine Ingredients Vaccines by Disease Chickenpox ... Typhoid Fever Whooping Cough (Pertussis) Yellow Fever Who and When Infants, Children, and Teens ...
Stone, John W; Thornburg, Natalie J; Blum, David L; Kuhn, Sam J; Crowe Jr, James E; Wright, David W
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)
Full Text Available Rotavirus, the most common cause of severe diarrhea and a leading cause of mortality in children, has been a priority target for vaccine development for the past several years. The first rotavirus vaccine licensed in the United States was withdrawn because of an association of the vaccine with intussusception. However, the need for a vaccine is greatest in the developing world, because the benefits of preventing deaths due to rotavirus disease are substantially greater than the risk of intussusception. Early vaccines were based on animal strains. More recently developed and licenced vaccines are either animal-human reassortants or are based on human strains. In India, two candidate vaccines are in the development process, but have not yet reached efficacy trials. Many challenges regarding vaccine efficacy and safety remain. In addition to completing clinical evaluations of vaccines in development in settings with the highest disease burden and virus diversity, there is also a need to consider alternative vaccine development strategies.
Milligan, Rachael; Paul, Mical; Richardson, Marty; Neuberger, Ami
Typhoid fever and paratyphoid fever continue to be important causes of illness and death, particularly among children and adolescents in south-central and southeast Asia. Two typhoid vaccines are widely available, Ty21a (oral) and Vi polysaccharide (parenteral). Newer typhoid conjugate vaccines are at varying stages of development and use. The World Health Organization has recently recommended a Vi tetanus toxoid (Vi-TT) conjugate vaccine, Typbar-TCV, as the preferred vaccine for all ages. To assess the effects of vaccines for preventing typhoid fever. In February 2018, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL, MEDLINE, Embase, LILACS, and mRCT. We also searched the reference lists of all included trials. Randomized and quasi-randomized controlled trials (RCTs) comparing typhoid fever vaccines with other typhoid fever vaccines or with an inactive agent (placebo or vaccine for a different disease) in adults and children. Human challenge studies were not eligible. Two review authors independently applied inclusion criteria and extracted data, and assessed the certainty of the evidence using the GRADE approach. We computed vaccine efficacy per year of follow-up and cumulative three-year efficacy, stratifying for vaccine type and dose. The outcome addressed was typhoid fever, defined as isolation of Salmonella enterica serovar Typhi in blood. We calculated risk ratios (RRs) and efficacy (1 - RR as a percentage) with 95% confidence intervals (CIs). In total, 18 RCTs contributed to the quantitative analysis in this review: 13 evaluated efficacy (Ty21a: 5 trials; Vi polysaccharide: 6 trials; Vi-rEPA: 1 trial; Vi-TT: 1 trial), and 9 reported on adverse events. All trials but one took place in typhoid-endemic countries. There was no information on vaccination in adults aged over 55 years of age, pregnant women, or travellers. Only one trial included data on children under two years of age.Ty21a vaccine (oral vaccine, three doses
Ogholikhan, Sina; Schwarz, Kathleen B.
Viral hepatitis is a serious health problem all over the world. However, the reduction of the morbidity and mortality due to vaccinations against hepatitis A and hepatitis B has been a major component in the overall reduction in vaccine preventable diseases. We will discuss the epidemiology, vaccine development, and post-vaccination effects of the hepatitis A and B virus. In addition, we discuss attempts to provide hepatitis D vaccine for the 350 million individuals infected with hepatitis B ...
Full Text Available The article describes the problem of pneumococcal infections (pneumonias, meningitis, otitis in children and adults. The modern opportunities of vaccinoprophylaxis and its usefulness in public health service are shown. The perspectives and questions on safety and effectiveness of pneumococcal conjugated 7-valent vaccine as the basic method of pneumococcal infections prophylaxis in infants and children from risk groups (with bronchial asthma, sickle-cell anemia, etc. are presented in details.Key words: children, pneumococcal infection, vaccination, pneumococcal conjugated 7-valent vaccine.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2009;8(4:79-83
Zimmerman, Richard K; Raviotta, Jonathan M; Nowalk, Mary Patricia; Moehling, Krissy K; Reis, Evelyn Cohen; Humiston, Sharon G; Lin, Chyongchiou Jeng
To report the results of an intervention using the 4 Pillars™ Practice Transformation Program (4 Pillars™ Program) to increase adolescent vaccinations including human papillomavirus vaccine (HPV) and influenza vaccines, which remain underutilized in this population. Eleven pediatric and family medicine practices, previously control sites from a randomized controlled cluster trial, with ≥50 adolescent patients participated. The 4 Pillars™ Program was the foundation of the intervention. De-identified demographic, office visit and vaccination data were derived from electronic medical record extractions for patients whose date of birth was 4/1/1997 to 4/1/2004 (ages 11-17years at baseline). Vaccination rates for HPV, influenza, tetanus-pertussis-diphtheria (Tdap) and meningococcal (MenACWY) vaccines were determined for all eligible patients pre- and post intervention (i.e., vaccination rates on 4/1/2015 and 4/30/2016). Among 9473 patients ages 11-17years at baseline (4/1/2015), mean pre-intervention vaccination rates for HPV initiation and completion, meningococcal, Tdap and influenza vaccines were below national levels. Rates increased significantly post intervention (P<0.001) for HPV initiation which increased 17.1 percentage points (PP) from 51.4%; HPV completion increased 14.8PP from 30.7%, meningococcal vaccine uptake increased 16.6PP from 79.1%, Tdap vaccine uptake increased 14.6PP from 76.9%. Influenza vaccine uptake did not increase significantly (2.3PP from 40.1%). In the regression using generalized estimating equations, odds of vaccination were higher for younger, non-white adolescents for all vaccines; being in a smaller practice decreased the odds of Tdap vaccination but increased the odds of influenza vaccination. Clinically and statistically significant improvements in HPV series initiation and completion, and meningococcal and Tdap vaccinations were observed in primary care practices implementing the 4 Pillars™ Practice Transformation Program
O'Brien, Megan A; Prosser, Lisa A; Paradise, Jack L; Ray, G Thomas; Kulldorff, Martin; Kurs-Lasky, Marcia; Hinrichsen, Virginia L; Mehta, Jyotsna; Colborn, D Kathleen; Lieu, Tracy A
New vaccines that offer protection against otitis media caused by nontypeable Haemophilus influenzae and by Moraxella catarrhalis are under development. However, the potential health benefits and economic effects of such candidate vaccines have not been systematically assessed. We created a computerized model to compare the projected benefits and costs of (1) the currently available 7-valent pneumococcal conjugate vaccine, (2) a candidate pneumococcal-nontypeable H influenzae vaccine that has been tested in Europe, (3) a hypothetical pneumococcal-nontypeable H influenzae-Moraxella vaccine, and (4) no vaccination. The clinical probabilities of acute otitis media and of otitis media with effusion were generated from multivariate analyses of data from 2 large health maintenance organizations and from the Pittsburgh Child Development/Otitis Media Study cohort. Other probabilities, costs, and quality-of-life values were derived from published and unpublished sources. The base-case analysis assumed vaccine dose costs of $65 for the 7-valent pneumococcal conjugate vaccine, $100 for the pneumococcal-nontypeable H influenzae vaccine, and $125 for the pneumococcal-nontypeable H influenzae-Moraxella vaccine. With no vaccination, we projected that 13.7 million episodes of acute otitis media would occur annually in US children aged 0 to 4 years, at an annual cost of $3.8 billion. The 7-valent pneumococcal conjugate vaccine was projected to prevent 878,000 acute otitis media episodes, or 6.4% of those that would occur with no vaccination; the corresponding value for the pneumococcal-nontypeable H influenzae vaccine was 3.7 million (27%) and for the pneumococcal-nontypeable H influenzae-Moraxella vaccine was 4.2 million (31%). Using the base-case vaccine costs, pneumococcal-nontypeable H influenzae vaccine use would result in net savings compared with nontypeable 7-valent pneumococcal conjugate use. Conversely, pneumococcal-nontypeable H influenzae-Moraxella vaccine use would not
Yen, Catherine; Tate, Jacqueline E; Hyde, Terri B; Cortese, Margaret M; Lopman, Benjamin A; Jiang, Baoming; Glass, Roger I; Parashar, Umesh D
Rotavirus is the leading cause of severe diarrhea among children rotavirus vaccines have been efficacious and effective, with many countries reporting substantial declines in diarrheal and rotavirus-specific morbidity and mortality. However, the full public health impact of these vaccines has not been realized. Most countries, including those with the highest disease burden, have not yet introduced rotavirus vaccines into their national immunization programs. Research activities that may help inform vaccine introduction decisions include (1) establishing effectiveness, impact, and safety for rotavirus vaccines in low-income settings; (2) identifying potential strategies to improve performance of oral rotavirus vaccines in developing countries, such as zinc supplementation; and (3) pursuing alternate approaches to oral vaccines, such as parenteral immunization. Policy- and program-level barriers, such as financial implications of new vaccine introductions, should be addressed to ensure that countries are able to make informed decisions regarding rotavirus vaccine introduction. PMID:24755452
Jacobson, Robert M; St Sauver, Jennifer L; Finney Rutten, Lila J
Vaccine refusal received a lot of press with the 2015 Disneyland measles outbreak, but vaccine refusal is only a fraction of a much larger problem of vaccine delay and hesitancy. Opposition to vaccination dates back to the 1800 s, Edward Jenner, and the first vaccine ever. It has never gone away despite the public's growing scientific sophistication. A variety of factors contribute to modern vaccine hesitancy, including the layperson's heuristic thinking when it comes to balancing risks and benefits as well as a number of other features of vaccination, including falling victim to its own success. Vaccine hesitancy is pervasive, affecting a quarter to a third of US parents. Clinicians report that they routinely receive requests to delay vaccines and that they routinely acquiesce. Vaccine rates vary by state and locale and by specific vaccine, and vaccine hesitancy results in personal risk and in the failure to achieve or sustain herd immunity to protect others who have contraindications to the vaccine or fail to generate immunity to the vaccine. Clinicians should adopt a variety of practices to combat vaccine hesitancy, including a variety of population health management approaches that go beyond the usual call to educate patients, clinicians, and the public. Strategies include using every visit to vaccinate, the creation of standing orders or nursing protocols to provide vaccination without clinical encounters, and adopting the practice of stating clear recommendations. Up-to-date, trusted resources exist to support clinicians' efforts in adopting these approaches to reduce vaccine hesitancy and its impact. Copyright © 2015 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.
McIntyre, Peter B.; O'Brien, Katherine L.; Greenwood, Brian; van de Beek, Diederik
Three bacteria-Haemophilus influenzae, Streptococcus pneumoniae, and Neisseria meningitidis-account for most acute bacterial meningitis. Measurement of the effect of protein-polysaccharide conjugate vaccines is most reliable for H influenzae meningitis because one serotype and one age group account
Impact of Haemophilus influenzae type b conjugate vaccine on bacterial meningitis in the Dominican Republic Impacto de la vacuna conjugada contra Haemophilus influenzae tipo b sobre la meningitis bacteriana en la República Dominicana
Ellen H. Lee
Full Text Available OBJECTIVES: Widespread use of Haemophilus influenzae type b (Hib vaccines has dramatically reduced the burden of Hib disease throughout the Americas. Few studies have evaluated the impact of Hib vaccination on non-culture-confirmed disease. This study analyzed trends in probable bacterial meningitis before and after the introduction of Hib vaccine in the Dominican Republic and estimated vaccine effectiveness against Hib meningitis. METHODS: Meningitis cases among children OBJETIVOS: El uso generalizado de la vacuna contra Haemophilus influenzae tipo b (Hib ha permitido reducir radicalmente la carga de enfermedad por Hib en las Américas. Pocos estudios han evaluado el impacto de la vacunación contra Hib sobre los casos no confirmados mediante cultivo. En este estudio se analizaron las tendencias en el número de casos probables de meningitis bacteriana antes y después de la introducción de la vacuna contra Hib en la República Dominicana y se estimó la eficacia de la vacuna contra la meningitis. MÉTODOS: Se identificaron los casos de meningitis en niños menores de 5 años a partir de los registros de ingreso del principal hospital pediátrico de Santo Domingo entre 1998 y 2004. Los casos de meningitis con probable etiología bacteriana se clasificaron según criterios de laboratorio; los casos confirmados contaban con cultivo bacteriano positivo o detección de antígenos específicos en el líquido cefalorraquídeo. Se calcularon las tasas de incidencia acumulada de casos confirmados y probables de meningitis en los niños que vivían en el Distrito Nacional. Los casos confirmados de meningitis por Hib se incorporaron a un estudio de casos y controles -pareados según la edad y el barrio de residencia- para calcular la eficacia de la vacuna. RESULTADOS: Antes de la introducción de la vacuna, la tasa anual de meningitis de posible etiología bacteriana era de 49 casos por 100 000 niños menores de 5 años; de los casos confirmados de
Hansen, Paul Robert
To produce antibodies against synthetic peptides it is necessary to couple them to a protein carrier. This chapter provides a nonspecialist overview of peptide-carrier conjugation. Furthermore, a protocol for coupling cysteine-containing peptides to bovine serum albumin is outlined....
Furst, J.E.; Laugesen, R.; Dastoor, P.; McNeill, C.
Full text: Conjugated polymers combine the electronic and optical properties of semiconductors with the processability of polymers. They contain a sequence of alternate single and double carbon bonds so that the overlap of unhybridised p z orbitals creates a delocalised ρ system which gives semiconducting properties with p-bonding (valence) and p* -antibonding (conduction) bands. Photoluminesence (PL) in conjugated polymers results from the radiative decay of singlet excitons confined to a single chain. The present work is the first in a series of studies in our laboratory that will characterize the optical properties of conjugated polymers. The experiment involves the illumination of thin films of conjugated polymer with UV light (I=360 nm) and observing the subsequent fluorescence using a custom-built, fluorescence spectrometer. Photoluminesence spectra provide basic information about the structure of the polymer film. A typical spectrum is shown in the accompanying figure. The position of the first peak is related to the polymer chain length and resolved multiple vibronic peaks are an indication of film structure and morphology. We will also present results related to the optical degradation of these materials when exposed to air and UV light
Hsiao, Shih-Chia; Francis, Matthew B.; Bertozzi, Carolyn; Mathies, Richard; Chandra, Ravi; Douglas, Erik; Twite, Amy; Toriello, Nicholas; Onoe, Hiroaki
The present invention provides conjugates of DNA and cells by linking the DNA to a native functional group on the cell surface. The cells can be without cell walls or can have cell walls. The modified cells can be linked to a substrate surface and used in assay or bioreactors.
Hsiao, Shih-Chia; Francis, Matthew B.; Bertozzi, Carolyn; Mathies, Richard; Chandra, Ravi; Douglas, Erik; Twite, Amy; Toriello, Nicholas; Onoe, Hiroaki
The present invention provides conjugates of DNA and cells by linking the DNA to a native functional group on the cell surface. The cells can be without cell walls or can have cell walls. The modified cells can be linked to a substrate surface and used in assay or bioreactors.
Data, Maps - SC Public Health Diseases and Conditions Flu Tuberculosis STD/HIV and Viral Hepatitis Zika Illnesses E. coli Listeriosis Salmonella Hepatitis A Shellfish Monitoring and Regulation Certified Shippers Vaccines Teen and Preteen Vaccines Vaccines Needed for School Admission Related Topics Perinatal Hepatitis
Jones, Lyn H.
Vaccines have typically been prepared using whole organisms. These are normally either attenuated bacteria or viruses that are live but have been altered to reduce their virulence, or pathogens that have been inactivated and effectively killed through exposure to heat or formaldehyde. However, using whole organisms to elicit an immune response introduces the potential for infections arising from a reversion to a virulent form in live pathogens, unproductive reactions to vaccine components or batch-to-batch variability. Synthetic vaccines, in which a molecular antigen is conjugated to a carrier protein, offer the opportunity to circumvent these problems. This Perspective will highlight the progress that has been achieved in developing synthetic vaccines using a variety of molecular antigens. In particular, the different approaches used to develop conjugate vaccines using peptide/proteins, carbohydrates and other small molecule haptens as antigens are compared.
Impacto de la vacuna conjugada en la incidencia de meningitis por Haemophilus influenzae en el Distrito Federal de Brasil: resultados de tres años de seguimiento Impact of anti-Hib conjugate vaccine on the incidence of Haemophilus influenzae meningitis in Brazil's Federal District: results of a three-year follow-up
Helen Selma de Abreu Freitas
developed after antibodies against the capsular component were identified. The objective of this paper was to estimate the impact that the vaccine against Hib has had in Brazil's Federal District since it was introduced in March of 1998. METHODS: Using population-based data obtained from Brazil's Federal District's Ministry of Health's Surveillance System, rates of incidence of meningitis during the three years that preceded and that followed the introduction of the anti-Hib vaccine were compared. Comparisons were also drawn between changes in the trends observed. RESULTS: A comparison of the data from the two periods showed a decrease of approximately 90% in the incidence of Hib meningitis, but no concomitant decrease in other forms of bacterial meningitis was noted. There was also a proportional increase in the number of cases among infants 6 months of age and under due to a drop in the incidence of the disease in children older than 6 months. CONCLUSION: As a result of the introduction of the conjugated anti-Hib vaccine in Brazil's Federal District, the incidence of Hib meningitis among children 7 months to 35 months of age dropped from 168 per 100 000 to 15 per 100 000 (91.1%.
Hu, Shun; Yu, Weili; Hu, Chunyang; Wei, Dong; Shen, Lijuan; Hu, Tao; Yi, Youjin
Mycobacterium tuberculosis (Mtb) is a serious fatal pathogen that causes tuberculosis (TB). Effective vaccination is urgently needed to deal with the serious threat from TB. Mtb-secreted protein antigens are important virulence determinants of Mtb with poor immunogenicity. Adjuvants and antigen delivery systems are thus highly desired to improve the immunogenicity of protein antigens. Inulin is a biocompatible polysaccharide (PS) adjuvant that can stimulate a strong cellular and humoral immunity. Bacterial capsular PS and haptens have been conjugated with cross-reacting material 197 (CRM 197 ) to improve their immunogenicity. CFP10 and TB10.4 were two Mtb-secreted immunodominant protein antigens. A CFP10-TB10.4 fusion protein (CT) was used as the antigen for covalent conjugation with the CRM 197 -inulin conjugate (CRM-inu). The resultant conjugate (CT-CRM-inu) elicited high CT-specific IgG titers, stimulated splenocyte proliferation and provoked the secretion of Th1-type and Th2-type cytokines. Conjugation with CRM-inu significantly prolonged the systemic circulation of CT and exposure to the immune system. Moreover, CT-CRM-inu showed no apparent toxicity to cardiac, hepatic and renal functions. Thus, conjugation of CT with CRM-inu provided an effective strategy for development of protein-based vaccines against Mtb infection. Copyright © 2017 Elsevier Ltd. All rights reserved.
People working on the CERN site who wish to be vaccinated may go to the Infirmary (ground-floor, bldg. 57), with their vaccine, without a prior appointment. The vaccine can be reimbursed directly by Uniqa providing you attach the receipt and the prescription that you will receive from the Medical Service the day of your injection at the infirmary. Ideally, the vaccination should take place between 1st October and 30th November 2007 (preferably between 14:00 and 16:00). CERN staff aged 50 or over are recommended to have influenza vaccinations. Vaccination is particularly important for those suffering from chronic lung, cardio-vascular or kidney problems, for diabetics and those convalescing from serious medical problems or after serious surgical operations. The Medical Service will not administer vaccines for family members or retired staff members, who must contact their normal family doctor. Medical Service
Maurizio de Martino
Full Text Available Vaccinating pregnant women in order to protect them, the fetus, and the child has become universal in no way at all. Prejudice in health professionals add to fears of women and their families. Both these feelings are not supported by even the smallest scientific data. Harmlessness for the mother and the child has been observed for seasonal, pandemic, or quadrivalent influenza, mono, combined polysaccharide or conjugated meningococcal or pneumococcal, tetanus toxoid, acellular pertussis, human papillomavirus, cholera, hepatitis A, Japanese encephalitis, rabies, anthrax, smallpox, yellow fever, mumps, measles and rubella combined, typhoid fever, inactivated or attenuated polio vaccines, and Bacillus Calmétte Guerin vaccines. Instead, the beneficial effects of influenza vaccine for the mother and the child as well as of pertussis vaccine for the child have been demonstrated. Obstetrician-gynecologists, general practitioners, and midwives must incorporate vaccination into their standard clinical care. Strong communication strategies effective at reducing parental vaccine hesitancy and approval of regulatory agencies for use of vaccines during pregnancy are needed. It must be clear that the lack of pre-licensure studies in pregnant women and, consequently, the lack of a statement about the use of the vaccine in pregnant women does not preclude its use in pregnancy.
Serotype distribution of pneumococci isolated from pediatric patients with acute otitis media and invasive infections, and potential coverage of pneumococcal conjugated vaccines Distribución de serotipos de neumococos aislados de pacientes pediátricos con otitis media aguda e infecciones invasivas y su cobertura potencial a través de vacunas conjugadas
Full Text Available A 16-month prospective, descriptive study was conducted on pneumococcal serotype distribution isolated from children with acute otitis media (AÜM and invasive infections (INV. Eighty-nine children with pneumococcal INV and 324 with a first episode of AOM were included. Bacterial pathogens (N = 326 were isolated from the middle-ear fluid of 250 patients. A total of 30 pneumococcal serotypes were identified. Prevalent serotypes were 14, 19A, 9V, 3, 19F, 6A, 23F, and 18C in AOM and 14, 1, 19A, 5, 12F, 6B, and 18C in INV. Potential coverage with PCV10 vaccine would be 46.5 % and 60.7 % for pneumococci involved in AOM and INV, respectively; it would be 71.7 % and 73 % with PCV13. PCV10, conjugated with a Haemophilus protein, would have an immunologic coverage of 39.9 % for AOM vs. 18.5 % with PCV13. However, differences in the prevention of INV were crucial for the decision to include the 13-valent vaccine in the national calendar for children less than two years old in Argentina.Se realizó un estudio prospectivo descriptivo sobre la distribución de serotipos de neumococos aislados de niños con otitis media aguda (OMA y con infecciones invasivas (INV en un período de 16 meses. Se incluyeron 89 niños con INV neumocócicas y 324 con un primer episodio de OMA. Trescientos cuarenta y seis patógenos se aislaron de las secreciones de oído medio obtenidas de 250 pacientes. Se identificaron 30 serotipos y los más prevalentes fueron el 14, 19A, 9V, 3, 19F, 6A, 23F y 18C en OMA y el 14, 1, 19A, 5, 12F, 6B y 18C en INV. La cobertura potencial con la vacuna PCV10 sería de 46,5 % y 60,7 % para neumococos involucrados en OMA y en INV, respectivamente; con la PCV13, esta sería de 71,7 % y 73 %. La PCV10 conjugada con una proteína de Haemophilus tendría una cobertura inmunológica del 39,9 % para OMA, contra una cobertura del 18,5 % de la PCV13. Sin embargo, las diferencias en la prevención de INV fueron determinantes a la hora de considerar
Poirot, P; Martin, J F
When Jonas Salk announced in the mid-50s the availability of a new vaccine against poliomyelitis, the world had the impression that it was now controlling infectious diseases. In fact, the success of this vaccine has been considerable and although some innovations lead to the launch of vaccines against flu, measles, rubella or mumps, the world vaccine market remained remarkably stable till the mid-80s. However, since 1984 (launch of the hepatitis B vaccine) there have been very substantial changes and further change is expected in the next ten years in the world market. Today, big companies are making a concentrated supply: Pasteur Mérieux with its subsidiary Connaught, SmithKline Beecham who acquired the Belgian company RIT, and Merck & Co. who is joining its forces with Pasteur Mérieux. Medium sized and small companies remain and reflect the situation of the past, but must work hard to secure their long term existence eventhough the world demand is going to double before the year 2000. Very substantial technological innovations explain to a large extent the development of the supply: progress in molecular biology, and particularly genetic engineering, lead to recombinant vaccines of which hepatitis B is the best example with worldwide sales in the range of $600 million a year. Similarly, conjugation technologies have allowed the development of new vaccines against meningitis, particularly Haemophilus influenzae type b. More recently, an efficacious vaccine against hepatitis A has been launched and many new products will be marketed in the next years against herpes, Lyme disease, and agents of other meningitis, etc.(ABSTRACT TRUNCATED AT 250 WORDS)
Aguado, M Teresa; Jodar, Luis; Granoff, Dan; Rabinovich, Regina; Ceccarini, Costante; Perkin, Gordon W
Polysaccharide vaccines had been used to control African meningitis epidemics for >30 years but with little or modest success, largely because of logistical problems in the implementation of reactive vaccination campaigns that are begun after epidemics are under way. After the major group A meningococcal meningitis epidemics in 1996-1997 (250,000 cases and 25,000 deaths), African ministers of health declared the prevention of meningitis a high priority and asked the World Health Organization (WHO) for help in developing better immunization strategies to eliminate meningitis epidemics in Africa. WHO accepted the challenge and created a project called Epidemic Meningitis Vaccines for Africa (EVA) that served as an organizational framework for external consultants, PATH, the US Centers for Disease Control and Prevention (CDC), and the Bill & Melinda Gates Foundation (BMGF). Consultations were initiated with major vaccine manufacturers. EVA commissioned a costing study/business plan for the development of new group A or A/C conjugate vaccines and explored the feasibility of developing these products as a public-private partnership. Representatives from African countries were consulted. They confirmed that the development of conjugate vaccines was a priority and provided information on preferred product characteristics. In parallel, a strategy for successful introduction was also anticipated and discussed. The expert consultations recommended that a group A meningococcal conjugate vaccine be developed and introduced into the African meningitis belt. The results of the costing study indicated that the "cost of goods" to develop a group A - containing conjugate vaccine in the United States would be in the range of US$0.35-$1.35 per dose, depending on composition (A vs A/C), number of doses/vials, and presentation. Following an invitation from BMGF, a proposal was submitted in the spring of 2001. In June 2001, BMGF awarded a grant of US$70 million to create the Meningitis
Full Text Available Although current influenza vaccines are effective in general, there is an urgent need for the development of new technologies to improve vaccine production timelines, capacities and immunogenicity. Herein, we describe the development of an influenza vaccine technology which enables recombinant production of highly efficient influenza vaccines in bacterial expression systems. The globular head domain of influenza hemagglutinin, comprising most of the protein's neutralizing epitopes, was expressed in E. coli and covalently conjugated to bacteriophage-derived virus-like particles produced independently in E.coli. Conjugate influenza vaccines produced this way were used to immunize mice and found to elicit immune sera with high antibody titers specific for the native influenza hemagglutinin protein and high hemagglutination-inhibition titers. Moreover vaccination with these vaccines induced full protection against lethal challenges with homologous and highly drifted influenza strains.
Full Text Available Viral hepatitis is a serious health problem all over the world. However, the reduction of the morbidity and mortality due to vaccinations against hepatitis A and hepatitis B has been a major component in the overall reduction in vaccine preventable diseases. We will discuss the epidemiology, vaccine development, and post-vaccination effects of the hepatitis A and B virus. In addition, we discuss attempts to provide hepatitis D vaccine for the 350 million individuals infected with hepatitis B globally. Given the lack of a hepatitis C vaccine, the many challenges facing the production of a hepatitis C vaccine will be shown, along with current and former vaccination trials. As there is no current FDA-approved hepatitis E vaccine, we will present vaccination data that is available in the rest of the world. Finally, we will discuss the existing challenges and questions facing future endeavors for each of the hepatitis viruses, with efforts continuing to focus on dramatically reducing the morbidity and mortality associated with these serious infections of the liver.
Ogholikhan, Sina; Schwarz, Kathleen B.
Viral hepatitis is a serious health problem all over the world. However, the reduction of the morbidity and mortality due to vaccinations against hepatitis A and hepatitis B has been a major component in the overall reduction in vaccine preventable diseases. We will discuss the epidemiology, vaccine development, and post-vaccination effects of the hepatitis A and B virus. In addition, we discuss attempts to provide hepatitis D vaccine for the 350 million individuals infected with hepatitis B globally. Given the lack of a hepatitis C vaccine, the many challenges facing the production of a hepatitis C vaccine will be shown, along with current and former vaccination trials. As there is no current FDA-approved hepatitis E vaccine, we will present vaccination data that is available in the rest of the world. Finally, we will discuss the existing challenges and questions facing future endeavors for each of the hepatitis viruses, with efforts continuing to focus on dramatically reducing the morbidity and mortality associated with these serious infections of the liver. PMID:26978406
People working on the CERN site who wish to be vaccinated against influenza may go to the Medical Service (ground floor, Bldg. 57) without an appointment (preferably between 14:00 and 16:00), PROVIDED THAT THEY BRING THEIR OWN VACCINE WITH THEM. Ideally, vaccination should take place between 1st October and 30th November 2006. The influenza vaccine is recommended for CERN staff aged 50 and over. Vaccination is particularly important for those suffering from chronic lung, cardio-vascular or kidney problems, for diabetics and for those convalescing from serious medical problems or major surgery. The Medical Service will not administer vaccines to family members or retired staff members, who must contact their family doctor. CERN Medical Service
CERN Medical Service
People working on the CERN site who wish to be vaccinated against influenza may go to the Medical Service (ground floor, Bldg. 57) without an appointment (preferably between 14:00 and 16:00), PROVIDED THAT THEY BRING THEIR OWN VACCINE WITH THEM. Ideally, vaccination should take place between 1st October and 30th November 2006. The influenza vaccine is recommended for CERN staff aged 50 and over. Vaccination is particularly important for those suffering from chronic lung, cardio-vascular or kidney problems, for diabetics and for those convalescing from serious medical problems or major surgery. The Medical Service will not administer vaccines to family members or retired staff members, who must contact their family doctor.CERN Medical Service
People working on the CERN site who wish to be vaccinated against influenza may go to the Medical Service (ground floor, Bldg. 57) without an appointment (preferably between 14:00 and 16:00), PROVIDED THAT THEY BRING THEIR OWN VACCINE WITH THEM. Ideally, vaccination should take place between 1st October and 30th November 2006. The influenza vaccine is recommended for CERN staff aged 50 and over. Vaccination is particularly important for those suffering from chronic lung, cardio-vascular or kidney problems, for diabetics and for those convalescing from serious medical problems or major surgery. The Medical Service will not administer vaccines to family members or retired staff members, who must contact their family doctor. CERN Medical Service
People working on the CERN site who wish to be vaccinated against influenza may go to the Medical Service (ground floor, Bldg. 57) without an appointment (preferably between 14:00 and 16:00), PROVIDED THAT THEY BRING THEIR OWN VACCINE WITH THEM. Ideally, vaccination should take place between 1st October and 30th November 2006. The influenza vaccine is recommended for CERN staff aged 50 and over. Vaccination is particularly important for those suffering from chronic lung, cardio-vascular or kidney problems, for diabetics and for those convalescing from serious medical problems or major surgery. The Medical Service will not administer vaccines to family members or retired staff members, who must contact their family doctor. CERN Medical service
Avaliação da resposta humoral à vacina pneumocócica 7-valente em crianças com Aids Evaluación de la vacuna neumocócica 7-valente en la respuesta humoral de niños con SIDA Evaluation of humoral response to heptavalent pneumococcal conjugate vaccine in HIV-infected children
Isabel de Camargo Costa
Paulo (Sureste de Brasil, en 2002-2003. La dosis de anticuerpos IgG contra los polisacáridos de la cápsula neumocócica fue realizada por medio de ensayo inmuno enzimático (ELISA. Los anticuerpos fueron dosificados inmediatamente antes y un mes después de la aplicación de la segunda dosis de la vacuna. Se utilizaron dos criterios para evaluar la respuesta a la vacuna: títulos de anticuerpos ? 1,3 ?g/mL en la serología post-inmunización y aumento ?4 veces en los títulos de la serología post-inmunización con relación a la pre-inmunización. RESULTADOS: Para el primer criterio (?1,3 ?g/mL, 26 (65% niños obtuvieron respuesta serológica con la vacuna, 12 (30% de ellas presentaron títulos de IgG post-inmunización en niveles de por lo menos 1,3 ?g/mL para todos los serotipos. Para el segundo criterio (incremento >4 veces en los títulos para cuatro serotipos o mas, se obtuvo respuesta serológica en 15 (37,5% niños. CONCLUSIONES: La respuesta frente a la vacuna fue considerada satisfactoria, con aumento estadísticamente significativo de los títulos geométricos promedios post-vacunales con relación a los pre-vacunales para todos los serotipos estudiados.OBJECTIVE: Invasive pneumococcal disease is a major cause of death in HIV-infected children. The objective of the study was to assess the quantitative antibody response to the seven pneumococcal serotypes of heptavalent pneumococcal conjugate vaccine in a group of HIV-infected children. METHODS: Study comprising 40 HIV-infected children aged between 2 and 9 years followed up in a specialized outpatient clinic in São Paulo, Brazil, between 2002 and 2003. Enzyme immunoassay (ELISA was used to measure IgG antibody titers against pneumococcus capsule. Antibodies were measured immediately before and 1 month after the second dose of the vaccine. Two response criteria were used: IgG titers >1.3 µg/mL in the post-immunization serology and an increase of at least 4-fold in post- compared to pre
Kristensen, Kim; Gyhrs, A; Lausen, B
OBJECTIVE: To evaluate the antibody response to a Haemophilus influenzae type b capsular polysaccharide (HibCP) tetanus toxoid (TT) conjugate vaccine (HibCP-TT) in preterm infants. SUBJECTS: Thirty-five healthy preterm infants with gestational ages (GA) from 27 to 36 weeks and birth weights from...
Payne, Richard; McDonald, David; Byrne, Scott
Due to changes in glycosyltransferase expression during tumorigenesis, the glycoproteins of cancer cells often carry highly truncated carbohydrate chains compared to those on healthy cells. These glycans are known as tumor-associated carbohydrate antigens, and are prime targets for use in vaccines for the prevention and treatment of cancer. Herein, we review the state-of-the-art in targeting the immune system towards tumor-associated glycopeptide antigens via synthetic self adjuvanting vaccines, in which the antigenic and adjuvanting moieties of the vaccines are present in the same molecule. The majority of the self-adjuvanting glycopeptide cancer vaccines reported to date employ antigens from mucin 1, a protein which is highly over-expressed and aberrantly glycosylated in many forms of cancer. The adjuvants used in these vaccines predominantly include lipopeptide- or lipoamino acid-based TLR2 agonists, although studies investigating stimulation of TLR9 and TLR4 are also discussed. Most of these adjuvants are highly lipophilic, and, upon conjugation to antigenic peptides, provide amphiphilic vaccine molecules. The amphiphilic nature of these vaccine constructs can lead to the formation of higher-order structures by vaccines in solution, which are likely to be important for their efficacy in vivo.
Talwar, G P; Diwan, M; Razvi, F; Malhotra, R
Vast changes are taking place in vaccinology consequent to the introduction of new technologies. Amongst the vaccines included in the Expanded Programme of Immunization (EPI), the pertussis vaccine has been replaced by acellular purified fractions devoid of side-effects. Non-pathogenic but immunogenic mutants of tetanus and diptheria toxins are likely to replace the toxoids. An effective vaccine against hepatitis B prepared by recombinant technology is in large-scale use. Conjugated vaccines against Haemophilus influenzae b, S. pneumococcus and meningococcus are now available, as also vaccines against mumps, rubella and measles. Combination vaccines have been devised to limit the number of injections. Vaccine delivery systems have been developed to deliver multiple doses of the vaccine at a single contact point. A genetically-engineered oral vaccine for typhoid imparts better and longer duration of immunity. Oral vaccines for cholera and other enteric infections are under clinical trials. The nose as a route for immunization is showing promise for mucosal immunity and for anti-inflammatory experimental vaccines against multiple sclerosis and insulin-dependent diabetes mellitus. The range of vaccines has expanded to include pathogens resident in the body such as Helicobacter pylori (duodenal ulcer), S. mutans (dental caries), and human papilloma virus (carcinoma of the cervix). An important progress is the recognition that DNA alone can constitute the vaccines, inducing both humoral and cell-mediated immune responses. A large number of DNA vaccines have been made and shown interesting results in experimental animals. Live recombinant vaccines against rabies and rinderpest have proven to be highly effective for controlling these infections in the field, and those for AIDS are under clinical trial. Potent adjuvants have added to the efficacy of the vaccines. New technologies have emerged to 'humanize' mouse monoclonals by genetic engineering and express these
Hunger, Miriam; Mutti, Elena; Rieder, Alexander
Design, synthesis, and structural characterization of a B12-octadecanucleotide are presented herein, a new organometallic B12-DNA conjugate. In such covalent conjugates, the natural B12 moiety may be a versatile vector for controlled in vivo delivery of oligonucleotides to cellular targets in hum...
diseases. Keywords. DNA vaccine, immune response, antibodies, infectious diseases. GENERAL .... tein vaccines require expensive virus/protein purification tech- niques as ... sphere continue to remain major health hazards in developing nations. ... significance since it can be produced at a very low cost and can be stored ...
Vaccination involves priming the immune system with an antigenic agent that mimics a virus or bacterium, which results in immunity against the “real” microorganism. Collective vaccination policies have played an important role in the control of infectious disease worldwide. They can serve the
Wagner, Ernst; Kircheis, Ralf; Crommelin, D.; Van Slooten, Maaike; Storm, Gert
The invention relates to a tumour vaccine with a tumour antigen base. In addition to a source of tumour antigens, the vaccine contains a release system for the delayed release of the active agent IFN- gamma , the active dose of IFN- gamma being 50 ng to 5 mu g. The IFN- gamma is released over a
Why get vaccinated?Rotavirus is a virus that causes diarrhea, mostly in babies and young children. The diarrhea can be severe, and lead ... and fever are also common in babies with rotavirus.Before rotavirus vaccine, rotavirus disease was a common ...
Hu, Yu; Luo, Shuying; Tang, Xuewen; Lou, Linqiao; Chen, Yaping; Guo, Jing
This study aimed to describe the disparities in immunization coverage between National Immunization Program (NIP) vaccines and non-NIP vaccines in Yiwu and to identify potential determinants. A face-to-face interview-based questionnaire survey among 423 migrant children born from 1 June 2010 to 31 May 2013 was conducted. Immunization coverage was estimated according to the vaccines scheduled at different age, the birth cohorts, and socio- demographic characteristics. Single-level logistic regression analysis was applied to identify the determinants of coverage of non-NIP vaccines. We found that NIP vaccines recorded higher immunization coverage compared with non-NIP vaccines (87.9100%– vs 0%-74.8%). Among the non-NIP vaccines, varicella vaccine (VarV) recorded the highest coverage of 85.4%, which was introduced in 1998; while 7-valent pneumococcal conjugate vaccine(PCV7) recorded the lowest coverage of 0% for primary series, which was introduced recently. Lower coverage rate of non-NIP vaccines was significantly associated with more siblings in household, shorter duration of living in the surveyed areas, lower family income, mother with a job, mother with poor awareness of vaccination, and mother with lower education level. We found the immunization coverage rate of non-NIP vaccines was significant lower than that of NIP vaccines. Expansion of NIP to include non-NIP vaccines can provide better protection against the vaccine preventable diseases through increased immunization coverage. PMID:25760670
Hu, Yu; Luo, Shuying; Tang, Xuewen; Lou, Linqiao; Chen, Yaping; Guo, Jing
This study aimed to describe the disparities in immunization coverage between National Immunization Program (NIP) vaccines and non-NIP vaccines in Yiwu and to identify potential determinants. A face-to-face interview-based questionnaire survey among 423 migrant children born from 1 June 2010 to 31 May 2013 was conducted. Immunization coverage was estimated according to the vaccines scheduled at different age, the birth cohorts, and socio- demographic characteristics. Single-level logistic regression analysis was applied to identify the determinants of coverage of non-NIP vaccines. We found that NIP vaccines recorded higher immunization coverage compared with non-NIP vaccines (87.9100%- vs 0%-74.8%). Among the non-NIP vaccines, varicella vaccine (VarV) recorded the highest coverage of 85.4%, which was introduced in 1998; while 7-valent pneumococcal conjugate vaccine(PCV7) recorded the lowest coverage of 0% for primary series, which was introduced recently. Lower coverage rate of non-NIP vaccines was significantly associated with more siblings in household, shorter duration of living in the surveyed areas, lower family income, mother with a job, mother with poor awareness of vaccination, and mother with lower education level. We found the immunization coverage rate of non-NIP vaccines was significant lower than that of NIP vaccines. Expansion of NIP to include non-NIP vaccines can provide better protection against the vaccine preventable diseases through increased immunization coverage.
Full Text Available Background: Although rigorous efforts have substantially decreased the malaria burden through decades, it still threatens the lives of millions of children. Development of an effective vaccine can provide important approach in malaria control strategies. Unfortunately, development of an effective vaccine for falciparum malaria has been hindered by the extreme complexity of malaria parasite biology, complex and diverse parasite genomes, and immune evasion by the parasites as well as the intricate nature of the parasites infection cycle. The aim of this review was to discuss the different approaches to malaria vaccine development until now.Methods: Scientific databases, including MEDLINE (via PubMed and SCOPUS were searched up to 30 Jan 2017 and the articles regarding malaria vaccine development were taken into examination.Results: Several strategies for malaria vaccine development including pre-erythrocytic vaccines, antibody-based subunit vaccines, vectored vaccines, whole sporozoite vaccines, genetically Attenuated parasites and sporozoite subunit vaccine, erythrocytic vaccines, sexual stage vaccine, transmission-blocking vaccine as well as synthetic peptides and conjugate vaccine has been introduced. However, the success has been limited thus far.Conclusion: Although development of malaria vaccine over the past 70 year has been continued, the discovery, development, and licensing of a malaria vaccine formulation, which meets safety, affordability, accessibility, applicability, and efficacy has not yet been achieved.
Conjugated pneumococal vaccines had a notable impact on prevention of invasive pneumococcal disease (IPD) in vacccinated and non vaccinated (herd immunity) populations. In Chile a 10 valent conjugated vaccine (PCV10) was introduced in the Nacional Immunization Program (NIP) in 2011, initially in a 3+1 schedule at 2, 4, 6 and 12 months of age, and since 2012 in a 2+1 schedule (2, 4 and 12 months). In prematures schedule 3+1 was maintained. No catch up or high risk groups vaccination strategies were used. The inclusion of PCV10 has reduced the rates of IPD; 66% in infants less than 12 months old and a 60% in 12-24 months old. After 3 years of the introduction of PCV10, no herd immunity has been seen. Serotype replacement shows an increase of ST 3 but not ST19A. Surveillance shows that another vaccine with 13 serotypes (PCV13) would cover an additional 5 to 10% of cases. The nule herd immunity and more extense coverage of PCV13, suggests that NIP should switch from PCV10 to PCV13.
Boyer, Herbert (Yale University, New Haven, Conn.). Conjugation in Escherichia coli. J. Bacteriol. 91:1767–1772. 1966.—The sex factor of Escherichia coli K-12 was introduced into an E. coli B/r strain by circumventing the host-controlled modification and restriction incompatibilities known to exist between these closely related strains. The sexual properties of the constructed F+ B strain and its Hfr derivatives were examined. These studies showed that the E. coli strain B/r F+ and Hfr derivatives are similar to the E. coli strain K-12 F+ and Hfr derivatives. However, the site of sex factor integration was found to be dependent on the host genome. PMID:5327905
Picado Valenzuela, Alfredo
This revision considered object the description of one of the materials with the greatest potential in the field of electrochromic (mainly in the visible region): the conjugated polymers (CP), area of enormous potential both now and in a short time ahead. The CP are insulating materials and organic semiconductors in a state not doped. They can be doped positively or negatively being observed a significant increase in the conductivity and being generated a color change in these materials. The understanding of how optical properties vary based on the chemical structure of the polymer or its mixtures and more precisely of the alternatives that can be entered into the conjugated system or π system to obtain a material that besides to be flexible, environmentally stable, presents the colored states. The revision was centred chiefly in the polypyrrole (Ppy), the polythiophene (PTh) and their derivatives such as poly (3.4-ethylenedioxythiophene) (PEDOT). The advantage of using monomers with variable structure, to adjust the composition of the copolymer, or to blend with the PC, allows to obtain a variety of colored states that can be modulated through the visible spectrum and even with applications to wavelengths outside of this region. Because the PC presented at least two different colored states can be varied continuously as a function of the voltage applied. In some cases, they may submit multicoloured statements, which offers a range of possibilities for their application in flexible electronic devices type screens and windows. Applications include smart windows, camouflage clothing and data screens. This type of material is emerging as one of the substitutes of the traditional inorganic semiconductor, with the advantage of its low cost, high flexibility and the possibility to generate multiple colors through the handling of the monomers in the structure and control of energy of his band gap. (author) [es
An, Myunggi; Liu, Haipeng
Amphiphilic vaccine based on lipid-polymer conjugates is a new type of vaccine capable of self-delivering to the immune system. When injected subcutaneously, amphiphilic vaccines efficiently target antigen presenting cells in the lymph nodes (LNs) via a unique albumin-mediated transport and uptake mechanism and induce potent humoral and cellular immune responses. However, whether this new type of vaccine can be administrated via a safe, convenient microneedle-based transdermal approach remains unstudied. For such skin barrier-disruption systems, a simple application of microneedle arrays (MNs) is desired to disrupt the stratum corneum, and for rapid and pain-free self-administration of vaccines into the skin, the anatomic place permeates with an intricate mesh of lymphatic vessels draining to LNs. Here the microneedle transdermal approach is combined with amphiphilic vaccines to create a simple delivery approach which efficiently traffic molecular vaccines into lymphatics and draining LNs. The rapid release of amphiphilic vaccines into epidermis upon application of dissolving MNs to the skin of mice generates potent cellular and humoral responses, comparable or superior to those elicited by traditional needle-based immunizations. The results suggest that the amphiphilic vaccines delivered by dissolving MNs can provide a simple and safer vaccination method with enhanced vaccine efficacy. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Rodrigues, Charlene M C; Pinto, Marta V; Sadarangani, Manish; Plotkin, Stanley A
Currently used vaccines have had major effects on eliminating common infections, largely by duplicating the immune responses induced by natural infections. Now vaccinology faces more complex problems, such as waning antibody, immunosenescence, evasion of immunity by the pathogen, deviation of immunity by the microbiome, induction of inhibitory responses, and complexity of the antigens required for protection. Fortunately, vaccine development is now incorporating knowledge from immunology, structural biology, systems biology and synthetic chemistry to meet these challenges. In addition, international organisations are developing new funding and licensing pathways for vaccines aimed at pathogens with epidemic potential that emerge from tropical areas. © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.
It is shown that by using the block-conjugate-gradient method several, say s, columns of the inverse Kogut-Susskind fermion matrix can be found simultaneously, in less time than it would take to run the standard conjugate-gradient algorithm s times. The method improves in efficiency relative to the standard conjugate-gradient algorithm as the fermion mass is decreased and as the value of the coupling is pushed to its limit before the finite-size effects become important. Thus it is potentially useful for measuring propagators in large lattice-gauge-theory calculations of the particle spectrum
Pedersen, M. K.; Sørensen, Nanna Skall; Heegaard, Peter M. H.
-based assay systems and in deciding whether a vaccine-induced antibody response will be protective. With ovalbumin as a carrier protein and a peptide (7.2NY) representing a 19 ammo acid sequence from the E. coli-derived Verotoxin 2e as a model hapten we investigated whether it was possible to influence...... ten dines at two-weeks intervals with low doses of the eight conjugates, Blood samples collected between each immunisation were analysed by ELISA for specific antibody titres and relative affinities. With both types of conjugations, the anti-peptide antibody titres increased in response to increasing...... for terminal conjugation. Thus, it appears that the molar ratio of a peptide and its carrier may affect the resulting antibody affinities, and that a conjugation ratio between a terminally Conjugated peptide and its carrier approaching one will result in relatively high antibody affinities. Furthermore...
Østerhus, Sven Frederick
The Cochrane Library was systematically searched for meta-analyses regarding influenza vaccination of various populations, both healthy and sick. An effect in reducing the number of cases of influenza, influenza-like illness or complications to influenza was found in some studies, but, generally......, the quality of the studies was low, and several studies lacked hard clinical endpoints. Data on adverse effects were scarce. More randomised controlled trials investigating the effects of influenza vaccination are warranted....
... Influenza Types Seasonal Avian Swine Variant Pandemic Other Flu Vaccine Safety Information Questions & Answers Language: English (US) ... safety of flu vaccines monitored? Egg Allergy Are flu vaccines safe? Flu vaccines have good safety record. ...
... Seasonal Avian Swine Variant Pandemic Other Thimerosal in Flu Vaccine Questions & Answers Language: English (US) Español Recommend ... and/or fungi from contaminating the vaccine. Do flu vaccines contain thimerosal? Flu vaccines in multi-dose ...
... an ENT Doctor Near You Ear Infection and Vaccines Ear Infection and Vaccines Patient Health Information News ... or may need reinsertion over time. What about vaccines? A vaccine is a preparation administered to stimulate ...
Xie, Renxuan; Lee, Youngmin; Aplan, Melissa; Caggiano, Nick; Gomez, Enrique; Colby, Ralph
Conjugated polymers, such as poly(3-hexylthiophene-2,5-diyl) (P3HT) and poly-((9,9-dioctylfluorene)-2,7-diyl-alt-[4,7-bis(thiophen-5-yl)-2,1,3-benzothiadiazole]-2',2''-diyl) (PFTBT), are widely used as hole and electron transport materials in a variety of electronic devices. However, fundamental knowledge regarding chain entanglements and nematic-to-isotropic transition is still lacking and are crucial to maximize charge transport properties. A systematic melt rheology study on P3HT with various molecular weights and regio regularities was performed. We find that the entanglement molecular weight Me is 5.0 kg/mol for regiorandom P3HT, but the apparent Me for regioregular P3HT is significantly higher. The difference is postulated to arise from the presence of a nematic phase only in regioregular P3HT. Analogously, PFTBT shows a clear rheological signature of the nematic-to-isotropic transition as a reversible sharp transition at 278 C. Shearing of this nematic phase leads to anisotropic crystalline order in PFTBT. We postulate that aligning the microstructure will impact charge transport and thereby advance the field of conducting polymers. National Science Foundation.
Full Text Available Abstract Background Recommendations from the World Health Organization (WHO are crucial to inform developing country decisions to use, or not, a new intervention. This article analysed the WHO policy development process to predict its course for a malaria vaccine. Methods The decision-making processes for one malaria intervention and four vaccines were classified through (1 consultations with staff and expert advisors to WHO's Global Malaria Programme (GMP and Immunization, Vaccines and Biologicals Department (IVB; (2 analysis of the procedures and recommendations of the major policy-making bodies of these groups; (3 interviews with staff of partnerships working toward new vaccine availability; and (4 review and analyses of evidence informing key policy decisions. Case description WHO policy formulation related to use of intermittent preventive treatment in infancy (IPTi and the following vaccine interventions: Haemophilus influenzae type b conjugate vaccine (Hib, pneumococcal conjugate vaccine (PCV, rotavirus vaccine (RV, and human papillomavirus vaccine (HPV, five interventions which had relatively recently been through systematic WHO policy development processes as currently constituted, was analysed. Required information was categorized in three areas defined by a recent WHO publication on development of guidelines: safety and efficacy in relevant populations, implications for costs and population health, and localization of data to specific epidemiological situations. Discussion and evaluation Data needs for a malaria vaccine include safety; the demonstration of efficacy in a range of epidemiological settings in the context of other malaria prevention interventions; and information on potential rebound in which disease increases subsequent to the intervention. In addition, a malaria vaccine would require attention to additional factors, such as costs and cost-effectiveness, supply and demand, impact of use on other interventions, and
Vemer, P.; Postma, M.J.
Objectives: The Dutch National Immunization Program offers the 10-valent pneumococcal conjugate vaccine (PCV10). Also licensed for use in the infant population is the 13-valent PCV (PCV13). To update cost-effectiveness (CE) estimates of PCV13 over PCV10, using current epidemiological and economic
African countries: a cross-country analysis of health systems' impacts ... Health and Development, London School of Hygiene and Tropical Medicine, .... from the post introduction evaluation methodology20. .... cine in Kenya, Ethiopia and Cameroon before and after ..... and Health Systems: Summary of Main Themes and.
Alternatives to small molecule or vaccine approaches to treating tuberculosis are rarely discussed. Attacking Mycobacterium tuberculosis in the granuloma represents a challenge. It is proposed that the conjugation of small molecules onto a monoclonal antibody that recognizes macrophage or lymphocytes cell surface receptors, might be a way to target the bacteria in the granuloma. This antibody drug conjugate approach is currently being used in 2 FDA approved targeted cancer therapies. The pros and cons of this proposal for further research are discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.
Rawat, Richa; Yu, Xiao-Hong; Sweet, Marie; Shanklin, John
Conjugated linolenic acids (CLNs), 18:3 Δ9,11,13, lack the methylene groups found between the double bonds of linolenic acid (18:3 Δ9,12,15). CLNs are produced by conjugase enzymes that are homologs of the oleate desaturases FAD2. The goal of this study was to map the domain(s) within the Momordica charantia conjugase (FADX) responsible for CLN formation. To achieve this, a series of Momordica FADX-Arabidopsis FAD2 chimeras were expressed in the Arabidopsis fad3fae1 mutant, and the transformed seeds were analyzed for the accumulation of CLN. These experiments identified helix 2 and the first histidine box as a determinant of conjugase product partitioning into punicic acid (18:3 Δ9cis,11trans,13cis) or α-eleostearic acid (18:3 Δ9cis,11trans,13trans). This was confirmed by analysis of a FADX mutant containing six substitutions in which the sequence of helix 2 and first histidine box was converted to that of FAD2. Each of the six FAD2 substitutions was individually converted back to the FADX equivalent identifying residues 111 and 115, adjacent to the first histidine box, as key determinants of conjugase product partitioning. Additionally, expression of FADX G111V and FADX G111V/D115E resulted in an approximate doubling of eleostearic acid accumulation to 20.4% and 21.2%, respectively, compared with 9.9% upon expression of the native Momordica FADX. Like the Momordica conjugase, FADX G111V and FADX D115E produced predominantly α-eleostearic acid and little punicic acid, but the FADX G111V/D115E double mutant produced approximately equal amounts of α-eleostearic acid and its isomer, punicic acid, implicating an interactive effect of residues 111 and 115 in punicic acid formation. PMID:22451660
D. А. Novikova
Full Text Available Combined vaccines containing non-cellular pertussis component and having low reactogenicity, increase vaccination coverage against controllable infections. However, the safety of vaccination in children dealing with health issues, as well as those having a history of premature infancy, requires additional research. The article presents reactogenicity analysis for the DTP-IPV/HIB pentavaccine during primary vaccination and revaccination of premature infants (n = 85, as well as vaccination of mature newborns (n = 1433 inoculated in accordance with the national Vaccination Calendar behind the schedule. The occurrence of post-vaccinal reactions in the premature infant group was the same as in the mature infant group and amounted to 41.2% and 45.0%; the occurrence of common reactions was 18.8% and 22.4%; local effects measured 25.8% and 27.9% respectively. Post-vaccinal reactions were either weak or moderate, not requiring treatment, and they would completely disappear by the end of the third post-vaccinal day. Simultaneous injection of pentavaccine and Hepatitis B vaccine and pneumococcal conjugate vaccine in children with a history of premature infancy, showed no influence during the post-vaccinal period. The reactogenicity of pentavaccine increased along with the vaccination ratio during the primary series of vaccinations.
The National Immunization Survey (NIS) monitors vaccination coverage among children aged 19-35 months using a random-digit-dialed sample of telephone numbers of households to evaluate childhood immunization programs in the United States. This report describes the 2010 NIS coverage estimates for children born during January 2007-July 2009. Nationally, vaccination coverage increased in 2010 compared with 2009 for ≥ 1 dose of measles, mumps, and rubella vaccine (MMR), from 90.0% to 91.5%; ≥ 4 doses of pneumococcal conjugate vaccine (PCV), from 80.4% to 83.3%; the birth dose of hepatitis B vaccine (HepB), from 60.8% to 64.1%; ≥ 2 doses of hepatitis A vaccine (HepA), from 46.6% to 49.7%; rotavirus vaccine, from 43.9% to 59.2%; and the full series of Haemophilus influenzae type b (Hib) vaccine, from 54.8% to 66.8%. Coverage for poliovirus vaccine (93.3%), MMR (91.5%), ≥ 3 doses HepB (91.8%), and varicella vaccine (90.4%) continued to be at or above the national health objective targets of 90% for these vaccines.* The percentage of children who had not received any vaccinations remained low (poverty status still exist. Maintaining high vaccination coverage levels is important to reduce the burden of vaccine-preventable diseases and prevent a resurgence of these diseases in the United States, particularly in undervaccinated populations.
Korbelik, Mladen; Banáth, Judit; Čiplys, Evaldas; Szulc, Zdzislaw; Bielawska, Alicja; Chen, Wei R.
Glycated chitosan (GC), a water soluble galactose-conjugated natural polysaccharide, has proven to be an effective immunoadjuvant for treatment of tumors based on laser thermal therapy. It was also shown to act as adjuvant for tumor therapy with high-intensity ultrasound and in situ photodynamic therapy (PDT). In the present study, GC was examined as potential adjuvant to PDT-generated cancer vaccine. Two other agents, pure calreticulin protein and acid ceramidase inhibitor LCL521, were also tested as prospective adjuvants for use in conjunction with PDT vaccines. Single treatment with GC, included with PDT vaccine cells suspension, improved the therapeutic efficacy when compared to vaccine alone. This attractive prospect of GC application remains to be carefully optimized and mechanistically elucidated. Both calreticulin and LCL521 proved also effective adjuvants when combined with PDT vaccine tumor treatment.
The paper reported an introductory research on possibilities of new glass `conjugate materials.` The report took up the structure and synthetic process of conjugate materials to be researched/developed, classified them according to structural elements on molecular, nanometer and cluster levels, and introduced the structures and functions. Further, as glasses with new functions to be proposed, the paper introduced transparent and high-strength glass used for houses and vehicles, light modulation glass which realizes energy saving and optical data processing, and environmentally functional glass which realizes environmental cleaning or high performance biosensor. An initial survey was also conducted on rights of intellectual property to be taken notice of in Japan and abroad in the present situation. Reports were summed up and introduced of Osaka National Research Institute, Electrotechnical Laboratory, and National Industrial Research Institute of Nagoya which are all carrying out leading studies of conjugate materials. 235 refs., 135 figs., 6 tabs.
Zhang Jian Shayne F
Full Text Available Abstract Background Pneumonia is the leading cause of child mortality worldwide. Streptococcus pneumoniae (SP or pneumococcus is estimated to cause 821,000 child deaths each year. It has over 90 serotypes, of which 7 to 13 serotypes are included in current formulations of pneumococcal conjugate vaccines that are efficacious in young children. To further reduce the burden from SP pneumonia, a vaccine is required that could protect children from a greater diversity of serotypes. Two different types of vaccines against pneumococcal pneumonia are currently at varying stages of development: a multivalent pneumococcal conjugate vaccine covering additional SP serotypes; and a conserved common pneumococcal protein antigen (PPA vaccine offering protection for all serotypes. Methods We used a modified CHNRI methodology for setting priorities in health research investments. This was done in two stages. In Stage I, we systematically reviewed the literature related to emerging SP vaccines relevant to several criteria of interest: answerability; efficacy and effectiveness; cost of development, production and implementation; deliverability, affordability and sustainability; maximum potential for disease burden reduction; acceptability to the end users and health workers; and effect on equity. In Stage II, we conducted an expert opinion exercise by inviting 20 experts (leading basic scientists, international public health researchers, international policy makers and representatives of pharmaceutical companies. The policy makers and industry representatives accepted our invitation on the condition of anonymity, due to sensitive nature of their involvement in such exercises. They answered questions from CHNRI framework and their “collective optimism” towards each criterion was documented on a scale from 0 to 100%. Results The experts expressed very high level of optimism (over 80% that low-cost polysaccharide conjugate SP vaccines would satisfy each of the 9
Embodiments of the present disclosure provide for conjugated polymer nanoparticle, method of making conjugated polymer nanoparticles, method of using conjugated polymer nanoparticle, polymers, and the like.
Habuchi, Satoshi; Piwonski, Hubert Marek; Michinobu, Tsuyoshi
Embodiments of the present disclosure provide for conjugated polymer nanoparticle, method of making conjugated polymer nanoparticles, method of using conjugated polymer nanoparticle, polymers, and the like.
Emrick, Todd; Russell, Thomas; Page, Zachariah; Liu, Yao
A conjugated polymer zwitterion includes repeating units having structure (I), (II), or a combination thereof ##STR00001## wherein Ar is independently at each occurrence a divalent substituted or unsubstituted C3-30 arylene or heteroarylene group; L is independently at each occurrence a divalent C1-16 alkylene group, C6-30arylene or heteroarylene group, or alkylene oxide group; and R1 is independently at each occurrence a zwitterion. A polymer solar cell including the conjugated polymer zwitterion is also disclosed.
Edible vaccines are sub-unit vaccines where the selected genes are introduced into the plants and the transgenic plant is then induced to manufacture the encoded protein. Edible vaccines are mucosal-targeted vaccines where stimulation of both systematic and mucosal immune network takes place. Foods under study ...
Ali, Asad; Jafri, Rabab Zehra; Messonnier, Nancy; Tevi-Benissan, Carol; Durrheim, David; Eskola, Juhani; Fermon, Florence; Klugman, Keith P; Ramsay, Mary; Sow, Samba; Zhujun, Shao; Bhutta, Zulfiqar; Abramson, Jon
A number of countries now include meningococcal vaccines in their routine immunization programs. This review focuses on different approaches to including meningococcal vaccines in country programs across the world and their effect on the burden of invasive meningococcal disease (IMD) as reflected by pre and post-vaccine incidence rates in the last 20 years. Mass campaigns using conjugated meningococcal vaccines have lead to control of serogroup C meningococcal disease in the UK, Canada, Australia, Spain, Belgium, Ireland, and Iceland. Serogroup B disease, predominant in New Zealand, has been dramatically decreased, partly due to the introduction of an outer membrane vesicle (OMV) vaccine. Polysaccharide vaccines were used in high risk people in Saudi Arabia and Syria and in routine immunization in China and Egypt. The highest incidence region of the meningitis belt initiated vaccination with the serogroup A conjugate vaccine in 2010 and catch-up vaccination is ongoing. Overall results of this vaccine introduction are encouraging especially in countries with a moderate to high level of endemic disease. Continued surveillance is required to monitor effectiveness in countries that recently implemented these programs. PMID:24548156
Bärnighausen, Till; Bloom, David E; Cafiero-Fonseca, Elizabeth T; O'Brien, Jennifer Carroll
Vaccination has led to remarkable health gains over the last century. However, large coverage gaps remain, which will require significant financial resources and political will to address. In recent years, a compelling line of inquiry has established the economic benefits of health, at both the individual and aggregate levels. Most existing economic evaluations of particular health interventions fail to account for this new research, leading to potentially sizable undervaluation of those interventions. In line with this new research, we set forth a framework for conceptualizing the full benefits of vaccination, including avoided medical care costs, outcome-related productivity gains, behavior-related productivity gains, community health externalities, community economic externalities, and the value of risk reduction and pure health gains. We also review literature highlighting the magnitude of these sources of benefit for different vaccinations. Finally, we outline the steps that need to be taken to implement a broad-approach economic evaluation and discuss the implications of this work for research, policy, and resource allocation for vaccine development and delivery.
Chiappini, Elena; Venturini, Elisabetta; Bonsignori, Francesca; Galli, Luisa; de Martino, Maurizio
The serogroup C meningococcal conjugate vaccine is available since 1999. In the absence of randomized controlled trials that support a specific schedule, each country has adopted different vaccination programmes. Hereby, we analyse positive and negative aspects of the different vaccination strategies. While waiting for the introduction of other antimeningococcal vaccines, covering also for the Group B meningococci, further studies on effectiveness of an optimal schedule to be adopted in European countries are needed. © 2010 The Author(s)/Journal Compilation © 2010 Foundation Acta Paediatrica.
Ngabo, Fidèle; Levin, Ann; Wang, Susan A; Gatera, Maurice; Rugambwa, Celse; Kayonga, Celestin; Donnen, Philippe; Lepage, Philippe; Hutubessy, Raymond
Detailed cost evaluations of delivery of new vaccines such as pneumococcal conjugate, human papillomavirus (HPV), and rotavirus vaccines in low and middle-income countries are scarce. This paper differs from others by comparing the costs of introducing multiple vaccines in a single country and then assessing the financial and economic impact at the time and implications for the future. The objective of the analysis was to understand the introduction and delivery cost per dose or per child of the three new vaccines in Rwanda to inform domestic and external financial resource mobilization. Start-up, recurrent, and capital costs from a government perspective were collected in 2012. Since pneumococcal conjugate and HPV vaccines had already been introduced, cost data for those vaccines were collected retrospectively while prospective (projected) costing was done for rotavirus vaccine. The financial unit cost per fully immunized child (or girl for HPV vaccine) of delivering 3 doses of each vaccine (without costs related to vaccine procurement) was $0.37 for rotavirus (RotaTeq(®)) vaccine, $0.54 for pneumococcal (Prevnar(®)) vaccine in pre-filled syringes, and $10.23 for HPV (Gardasil (®)) vaccine. The financial delivery costs of Prevnar(®) and RotaTeq(®) were similar since both were delivered using existing health system infrastructure to deliver infant vaccines at health centers. The total financial cost of delivering Gardasil(®) was higher than those of the two infant vaccines due to greater resource requirements associated with creating a new vaccine delivery system in for a new target population of 12-year-old girls who have not previously been served by the existing routine infant immunization program. The analysis indicates that service delivery strategies have an important influence on costs of introducing new vaccines and costs per girl reached with HPV vaccine are higher than the other two vaccines because of its delivery strategy. Documented information
Home; Journals; Resonance – Journal of Science Education; Volume 13; Issue 8. Conjugal Pairing in Escherichia Coli. Joshua Lederberg. Classics Volume 13 Issue 8 August 2008 pp 793-794. Fulltext. Click here to view fulltext PDF. Permanent link: https://www.ias.ac.in/article/fulltext/reso/013/08/0793-0794 ...
Bahl, Martin Iain; Hansen, Lars H.; Sørensen, Søren Johannes
Are plasmids selfish parasitic DNA molecules or an integrated part of the bacterial genome? This chapter reviews the current understanding of the persistence mechanisms of conjugative plasmids harbored by bacterial cells and populations. The diversity and intricacy of mechanisms affecting the suc...
Ortega, James M.
The effect of orderings on the rate of convergence of the conjugate gradient method with SSOR or incomplete Cholesky preconditioning is examined. Some results also are presented that help to explain why red/black ordering gives an inferior rate of convergence.
Bai, Yingnan; Rottwinkel, Gregor; Feng, Juan; Liu, Yiyao; Lamparter, Tilman
Bacterial conjugation, the transfer of single stranded plasmid DNA from donor to recipient cell, is mediated through the type IV secretion system. We performed conjugation assays using a transmissible artificial plasmid as reporter. With this assay, conjugation in Agrobacterium fabrum was modulated by the phytochromes Agp1 and Agp2, photoreceptors that are most sensitive in the red region of visible light. In conjugation studies with wild-type donor cells carrying a pBIN-GUSINT plasmid as reporter that lacked the Ti (tumor inducing) plasmid, no conjugation was observed. When either agp1(-) or agp2(-) knockout donor strains were used, plasmid DNA was delivered to the recipient, indicating that both phytochromes suppress conjugation in the wild type donor. In the recipient strains, the loss of Agp1 or Agp2 led to diminished conjugation. When wild type cells with Ti plasmid and pBIN-GUS reporter plasmid were used as donor, a high rate of conjugation was observed. The DNA transfer was down regulated by red or far-red light by a factor of 3.5. With agp1(-) or agp2(-) knockout donor cells, conjugation in the dark was about 10 times lower than with the wild type donor, and with the double knockout donor no conjugation was observed. These results imply that the phytochrome system has evolved to inhibit conjugation in the light. The decrease of conjugation under different temperature correlated with the decrease of phytochrome autophosphorylation. Copyright © 2015 Elsevier B.V. All rights reserved.
REVIEW ARTICLE Conjugated Hyperbilirubinaemia in Early Infancy. AOK Johnson. Abstract. Conjugated hyperbilirubinaemia exists when the conjugated serum bilirubin level is more than 2 mg/dl or more than 20 per cent of the total serum bilirubin. It is always pathological in early infancy. The causes are many and diverse ...
Yunus, Ali A.; Lima, Christopher D.
SUMO conjugation to protein substrates requires the concerted action of a dedicated E2 ubiquitin conjugation enzyme (Ubc9) and associated E3 ligases. Although Ubc9 can directly recognize and modify substrate lysine residues that occur within a consensus site for SUMO modification, E3 ligases can redirect specificity and enhance conjugation rates during SUMO conjugation in vitro and in vivo. In this chapter, we will describe methods utilized to purify SUMO conjugating enzymes and model substrates which can be used for analysis of SUMO conjugation in vitro. We will also describe methods to extract kinetic parameters during E3-dependent or E3-independent substrate conjugation. PMID:19107417
Full Text Available A vaccine to prevent infections from the emerging Neisseria meningitidis X (MenX is becoming an urgent issue. Recently MenX capsular polysaccharide (CPS fragments conjugated to CRM197 as carrier protein have been confirmed at preclinical stage as promising candidates for vaccine development. However, more insights about the minimal epitope required for the immunological activity of MenX CPS are needed. We report herein the chemical conjugation of fully synthetic MenX CPS oligomers (monomer, dimer, and trimer to CRM197. Moreover, improvements in some crucial steps leading to the synthesis of MenX CPS fragments are described. Following immunization with the obtained neoglycoconjugates, the conjugated trimer was demonstrated as the minimal fragment possessing immunogenic activity, even though significantly lower than a pentadecamer obtained from the native polymer and conjugated to the same protein. This finding suggests that oligomers longer than three repeating units are possibly needed to mimic the activity of the native polysaccharide.
Brueggemann, Angela B; Pai, Rekha; Crook, Derrick W; Beall, Bernard
The heptavalent pneumococcal conjugate vaccine (PCV7) was introduced in the United States (US) in 2000 and has significantly reduced invasive pneumococcal disease; however, the incidence of nonvaccine serotype invasive disease, particularly due to serotype 19A, has increased. The serotype 19A increase can be explained in part by expansion of a genotype that has been circulating in the US prior to vaccine implementation (and other countries since at least 1990), but also by the emergence of a novel "vaccine escape recombinant" pneumococcal strain. This strain has a genotype that previously was only associated with vaccine serotype 4, but now expresses a nonvaccine serotype 19A capsule. Based on prior evidence for capsular switching by recombination at the capsular locus, the genetic event that resulted in this novel serotype/genotype combination might be identifiable from the DNA sequence of individual pneumococcal strains. Therefore, the aim of this study was to characterise the putative recombinational event(s) at the capsular locus that resulted in the change from a vaccine to a nonvaccine capsular type. Sequencing the capsular locus flanking regions of 51 vaccine escape (progeny), recipient, and putative donor pneumococci revealed a 39 kb recombinational fragment, which included the capsular locus, flanking regions, and two adjacent penicillin-binding proteins, and thus resulted in a capsular switch and penicillin nonsusceptibility in a single genetic event. Since 2003, 37 such vaccine escape strains have been detected, some of which had evolved further. Furthermore, two new types of serotype 19A vaccine escape strains emerged in 2005. To our knowledge, this is the first time a single recombinational event has been documented in vivo that resulted in both a change of serotype and penicillin nonsusceptibility. Vaccine escape by genetic recombination at the capsular locus has the potential to reduce PCV7 effectiveness in the longer term.
... During Pregnancy Frequently Asked Questions about Vaccine Recalls Historical Vaccine Safety Concerns FAQs about GBS and Menactra ... CISA Resources for Healthcare Professionals Evaluation Current Studies Historical Background 2001-12 Publications Technical Reports Vaccine Safety ...
... for Biologics Evaluation & Research Vaccine Adverse Events Vaccine Adverse Events Share Tweet Linkedin Pin it More sharing ... in the primary immunization series in infants Report Adverse Event Report a Vaccine Adverse Event Contact FDA ( ...
Chettri, Jiwan Kumar
vaccines have reduced the need for usage of antibiotics with more than 99 % since the 1980s. Fish can be vaccinated by three different administration routes: injection, immersion and oral vaccination. Injection vaccination (intraperitoneal injection of vaccine) is the most time consuming and labor...... intensive method, which however, provides the best protection of the fish. Immersion vaccination is used for immunization of a high number of small fish is cost-efficient and fast (30 sec immersion into vaccine). Oral vaccination (vaccine in feed) is the least efficient. As in higher vertebrates fish...... respond to vaccination by increasing the specific antibody titer and by activating the cellular responses. My talk will cover vaccination methods in fish, immune responses and some adverse effect of oil-adjuvanted vaccines in fish with reference to our work in rainbow trout, Oncorhynchus mykiss....
Why get vaccinated?HPV vaccine prevents infection with human papillomavirus (HPV) types that are associated with cause ... at http://www.cdc.gov/hpv. HPV Vaccine (Human Papillomavirus) Information Statement. U.S. Department of Health and ...
Full Text Available Malawi introduced pneumococcal conjugate vaccine (PCV13 and monovalent rotavirus vaccine (RV1 in 2011 and 2012 respectively, and is planning the introduction of a second-dose measles vaccine (MV. We assessed predictors of availability, uptake and timeliness of these vaccines in a rural Malawian setting.Commencing on the first date of PCV13 eligibility we conducted a prospective population-based birth cohort study of 2,616 children under demographic surveillance in Karonga District, northern Malawi who were eligible for PCV13, or from the date of RV1 introduction both PCV13 and RV1. Potential predictors of vaccine uptake and timeliness for PCV13, RV1 and MV were analysed respectively using robust Poisson and Cox regression.Vaccine coverage was high for all vaccines, ranging from 86.9% for RV1 dose 2 to 95.4% for PCV13 dose 1. Median time delay for PCV13 dose 1 was 17 days (IQR 7-36, 19 days (IQR 8-36 for RV1 dose 1 and 20 days (IQR 3-46 for MV. Infants born to lower educated or farming mothers and those living further away from the road or clinic were at greater risk of being not fully vaccinated and being vaccinated late. Delays in vaccination were also associated with non-facility birth. Vaccine stock-outs resulted in both a delay in vaccine timeliness and in a decrease in completion of schedule.Despite high vaccination coverage in this setting, delays in vaccination were common. We identified programmatic and socio-demographic risk factors for uptake and timeliness of vaccination. Understanding who remains most vulnerable to be unvaccinated allows for focussed delivery thereby increasing population coverage and maximising the equitable benefits of universal vaccination programmes.
To avoid the risk of vaccine-associated paralytic poliomyelitis (VAPP) and polio outbreaks due to circulating vaccine-derived polioviruses, an inactivated poliovirus vaccine (IPV) was introduced for routine immunization in a number of countries with a low risk of polio outbreaks. Currently, production and marketing of a standalone conventional IPV and two diphtheria-pertussis-tetanus-IPV (Sabin-derived IPV; sIPV) products have been submitted, and it is expected that the IPV products will be introduced in Japan in the autumn of 2012. At the same time, a decline in the OPV immunization rate became apparent in Japan due to serious public concerns about a remaining risk of VAPP and introduction of IPV in the near future. Therefore, the recent development of polio immunity gaps should be carefully monitored, and surveillance of suspected polio cases and laboratory diagnosis of polioviruses have to be intensified for the transition period from OPV to IPV in Japan. The development of sIPV is one of the most realistic options to introduce affordable IPV to developing countries. In this regard, further clinical studies on its efficacy, safety, and interchangeability of sIPV will be needed after the introduction of the sIPV products, which will be licensed in Japan for the first time in the world.
... a combination product containing Haemophilus influenzae type b, Hepatitis B Vaccine) ... combination product containing Diphtheria, Tetanus Toxoids, Acellular Pertussis, Hepatitis B, Polio Vaccine)
Vijayakumar, Subramaniyan; Ramesh, Venkatachalam; Prabhu, Srinivasan; Manogar, Palani
Reverse vaccinology method was used to predict the monovalent peptide vaccine candidate to produce antibodies for therapeutic purpose and to predict tetravalent vaccine candidate to act as a common vaccine to cover all the fever dengue virus serotypes. Envelope (E)-proteins of DENV-1-4 serotypes were used for vaccine prediction using NCBI, Uniprot/Swissprot, Swiss-prot viewer, VaxiJen V2.0, TMHMM, BCPREDS, Propred-1, Propred and MHC Pred,. E-proteins of DENV-1-4 serotypes were identified as antigen from which T cell epitopes, through B cell epitopes, were predicted to act as peptide vaccine candidates. Each selected T cell epitope of E-protein was confirmed to act as vaccine and to induce complementary antibody against particular serotype of dengue virus. Chimeric tetravalent vaccine was formed by the conjugation of four vaccines, each from four dengue serotypes to act as a common vaccine candidate for all the four dengue serotypes. It can be justifiably concluded that the monovalent 9-mer T cell epitope for each DENV serotypes can be used to produce specific antibody agaomst dengue virus and a chimeric common tetravalent vaccine candidate to yield a comparative vaccine to cover any of the four dengue virus serotype. This vaccine is expected to act as highly immunogenic against preventing dengue fever.
Ngcobo, Ntombenhle Judith; Kamupira, Mercy G
Vaccines have greatly contributed to the control of vaccine-preventable diseases and to human development. Efforts by many countries to introduce new vaccines are a significant move towards achieving the sustainable development goal for health. However, effective vaccine supply chains that ensure an uninterrupted supply of vaccines are pivotal to attaining universal access to life-saving vaccines and sustainable development. The introduction of new vaccines puts a strain on supply chains; South Africa (SA) is no exception, as there are indications of vaccine stock-outs in clinics. To establish the status of vaccine availability and associated factors in government health facilities of Tshwane Health District in Gauteng Province, SA. A cross-sectional study was conducted in a sample of randomly selected government clinics in the Tshwane health district of Gauteng Province. Data were collected using a structured measurement instrument in participating clinics. Data were analysed using Excel-based software (Microsoft, USA). A total of 31 clinics participated. In the preceding 12 months, clinics had experienced vaccine stock-outs, especially of the three newer vaccines: pneumococcal conjugate vaccine, rotavirus and Pentaxim. These were also out of stock for a long duration; for over 2 weeks in a majority of clinics. The causes of vaccine stock-outs were: poor management of stock, district depot out of stock, unreliable deliveries, lack of pharmacy assistants and limited fridge capacity. Further burdening the situation is the ineffective emergency-ordering system. Significant shortages of vaccines, which are essential drugs, occur in Tshwane government clinics. Vaccine supply chain issues and vaccine shortages should be treated as a priority at all levels of the healthcare system; therefore, a similar study should be conducted at national level. It is recommended that the vaccine supply chain should be restructured and overhauled with the use of advances in technology
Ntombenhle Judith Ngcobo
Full Text Available Background. Vaccines have greatly contributed to the control of vaccine-preventable diseases and to human development. Efforts by many countries to introduce new vaccines are a significant move towards achieving the sustainable development goal for health. However, effective vaccine supply chains that ensure an uninterrupted supply of vaccines are pivotal to attaining universal access to life-saving vaccines and sustainable development. The introduction of new vaccines puts a strain on supply chains; South Africa (SA is no exception, as there are indications of vaccine stock-outs in clinics. Objective. To establish the status of vaccine availability and associated factors in government health facilities of Tshwane Health District in Gauteng Province, SA. Methods. A cross-sectional study was conducted in a sample of randomly selected government clinics in the Tshwane health district of Gauteng Province. Data were collected using a structured measurement instrument in participating clinics. Data were analysed using Excel-based software (Microsoft, USA. Results. A total of 31 clinics participated. In the preceding 12 months, clinics had experienced vaccine stock-outs, especially of the three newer vaccines: pneumococcal conjugate vaccine, rotavirus and Pentaxim. These were also out of stock for a long duration; for over 2 weeks in a majority of clinics. The causes of vaccine stock-outs were: poor management of stock, district depot out of stock, unreliable deliveries, lack of pharmacy assistants and limited fridge capacity. Further burdening the situation is the ineffective emergency-ordering system. Conclusion. Significant shortages of vaccines, which are essential drugs, occur in Tshwane government clinics. Vaccine supply chain issues and vaccine shortages should be treated as a priority at all levels of the healthcare system; therefore, a similar study should be conducted at national level. It is recommended that the vaccine supply chain should
Full Text Available Immunogenicity and reactogenicity of the combined diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae type b (Hib conjugate vaccine (DTPa-IPV/Hib, Infanrix™-IPV + Hib was assessed when co-administered with hepatitis B (HBV vaccine. Seventy healthy infants received DTPa-IPV/Hib at 1.5, 3.5, 6 and 15–18 months, and HBV at birth, 1.5, 6 and 15–18 months of age. Serological responses were assessed. Diphtheria, tetanus, Hib and pertussis seroprotection/seropositivity rates were 100% after primary vaccination. Post-primary immune responses to poliovirus could not be evaluated for technical reasons. However, after the booster dose, seroprotection/seropositivity rates, including poliovirus, were 100%. Over 95% were seroprotected against HBV. Post-booster geometric mean antibody concentrations/titers (GMC/GMTs rose from 14-fold to 45-fold, indicating effective priming against all antigens, including polioviruses. DTPa-IPV/Hib was well tolerated alone or co-administered with HBV. No serious adverse events were considered related to vaccination. Primary and booster vaccination with combined DTPa-IPV/Hib and HBV was immunogenic and well tolerated. Combination vaccines enable vaccine providers to conveniently provide routine pediatric immunizations, with minimal discomfort.
Full Text Available Antibody-antigen conjugates, which promote antigen-presentation by dendritic cells (DC by means of targeted delivery of antigen to particular DC subsets, represent a powerful vaccination approach. To ensure immunity rather than tolerance induction the co-administration of a suitable adjuvant is paramount. However, co-administration of unlinked adjuvant cannot ensure that all cells targeted by the antibody conjugates are appropriately activated. Furthermore, antigen-presenting cells (APC that do not present the desired antigen are equally strongly activated and could prime undesired responses against self-antigens. We, therefore, were interested in exploring targeted co-delivery of antigen and adjuvant in cis in form of antibody-antigen-adjuvant conjugates for the induction of anti-tumour immunity. In this study, we report on the assembly and characterization of conjugates consisting of DEC205-specific antibody, the model antigen ovalbumin (OVA and CpG oligodeoxynucleotides (ODN. We show that such conjugates are more potent at inducing cytotoxic T lymphocyte (CTL responses than control conjugates mixed with soluble CpG. However, our study also reveals that the nucleic acid moiety of such antibody-antigen-adjuvant conjugates alters their binding and uptake and allows delivery of the antigen and the adjuvant to cells partially independently of DEC205. Nevertheless, antibody-antigen-adjuvant conjugates are superior to antibody-free antigen-adjuvant conjugates in priming CTL responses and efficiently induce anti-tumour immunity in the murine B16 pseudo-metastasis model. A better understanding of the role of the antibody moiety is required to inform future conjugate vaccination strategies for efficient induction of anti-tumour responses.
Saluja, Vinay; Hinrichs, Wouter L. J.; Frijlink, Henderik W.
Since last year influenza pandemic has struck again after 40 years, this is the right moment to discuss the different available formulation options for influenza vaccine. Looking back to the last 4 decades, most vaccines are still formulated as liquid solution. These vaccines have shown a poor
The aim of this thesis was to first assess nasopharyngeal bacterial carriage to evaluate population effects after introduction of PCV7 in the NIP in 2006 and to assess the potential impact of PCV10 as introduced in 2011 on carriage of NTHi in a randomized trial (Part One) and second, to assess
... high or when infection would pose a high risk to the mother or baby, vaccination with a live vaccine is discussed. If there ... and benefits. For some diseases the benefit of vaccination outweighs any risks that may be associated with the vaccine. What ...
Vaccines have a history that started late in the 18th century. From the late 19th century, vaccines could be developed in the laboratory. However, in the 20th century, it became possible to develop vaccines based on immunologic markers. In the 21st century, molecular biology permits vaccine development that was not possible before.
Vaccines have a history that started late in the 18th century. From the late 19th century, vaccines could be developed in the laboratory. However, in the 20th century, it became possible to develop vaccines based on immunologic markers. In the 21st century, molecular biology permits vaccine development that was not possible before.
M. K. Mansoor, S. U. Rahman, I. Hussain, M. H. Rasool and M. A. Zahoor
Full Text Available An indirect enzyme-linked immunosorbent assay (ELISA was performed for the detection of antibodies against Egg Drop Syndrome (EDS virus. Virus identification was done through haemaggluti- nation inhibition (HI test using known antisera. Antichicken immunoglobulins were raised in goats and purified by ammonium sulphate precipitation technique. These goat-antichicken immunoglobulins were conjugated with horseradish peroxidase. Twenty-seven serum samples were collected from a layers flock vaccinated against EDS and specific antibodies were determined by using a horseradish conjugate.
Combination vaccines have been introduced in Mexico. The national immunization program has incorporated the measles-mumps-rubella (MMR) vaccines in 1998, and the pentavalent vaccine in 1999. The two categories of antigen composition in combination vaccines are: 1) multiple different antigenic types of a single pathogen, such as the 23 valent pneumococcal polysaccharide vaccine, and 2) antigens from different pathogens causing different diseases, such as the DPT and MMR vaccines. Pentavalent vaccines are included in the second category. The vaccine protects against diphtheria, tetanus, pertussis, hepatitis B, and other diseases produced by Haemophilus influenzae type b (Hib). Combined diphtheria, tetanus, pertussis, hepatitis B, and Haemophilus influenza type b (DTP-HB/Hib) vaccine has been distributed to 87% of Mexican children under 1 year of age. Over 800,000 doses of pentavalent vaccine have been administered.
Vaccines are considered as one of the major contributions of the 20th century and one of the most cost effective public health interventions. The International Vaccine Institute has as a mission to discover, develop and deliver new and improved vaccines against infectious diseases that affects developing nations. If Louis Pasteur is known across the globe, vaccinologists like Maurice Hilleman, Jonas Salk and Charles Mérieux are known among experts only despite their contribution to global health. Thanks to a vaccine, smallpox has been eradicated, polio has nearly disappeared, Haemophilus influenzae B, measles and more recently meningitis A are controlled in many countries. While a malaria vaccine is undergoing phase 3, International Vaccine Institute, in collaboration with an Indian manufacturer has brought an oral inactivated cholera vaccine to pre-qualification. The field of vaccinology has undergone major changes thanks to philanthropists such as Bill and Melinda Gates, initiatives like the Decade of Vaccines and public private partnerships. Current researches on vaccines have more challenging targets like the dengue viruses, malaria, human immunodeficiency virus, the respiratory syncytial virus and nosocomial diseases. Exciting research is taking place on new adjuvants, nanoparticles, virus like particles and new route of administration. An overcrowded infant immunization program, anti-vaccine groups, immunizing a growing number of elderlies and delivering vaccines to difficult places are among challenges faced by vaccinologists and global health experts.
Yaesoubi, Reza; Trotter, Caroline; Colijn, Caroline; Yaesoubi, Maziar; Colombini, Anaïs; Resch, Stephen; Kristiansen, Paul A; LaForce, F Marc; Cohen, Ted
The introduction of a conjugate vaccine for serogroup A Neisseria meningitidis has dramatically reduced disease in the African meningitis belt. In this context, important questions remain about the performance of different vaccine policies that target remaining serogroups. Here, we estimate the health impact and cost associated with several alternative vaccination policies in Burkina Faso. We developed and calibrated a mathematical model of meningococcal transmission to project the disability-adjusted life years (DALYs) averted and costs associated with the current Base policy (serogroup A conjugate vaccination at 9 months, as part of the Expanded Program on Immunization [EPI], plus district-specific reactive vaccination campaigns using polyvalent meningococcal polysaccharide [PMP] vaccine in response to outbreaks) and three alternative policies: (1) Base Prime: novel polyvalent meningococcal conjugate (PMC) vaccine replaces the serogroup A conjugate in EPI and is also used in reactive campaigns; (2) Prevention 1: PMC used in EPI and in a nationwide catch-up campaign for 1-18-year-olds; and (3) Prevention 2: Prevention 1, except the nationwide campaign includes individuals up to 29 years old. Over a 30-year simulation period, Prevention 2 would avert 78% of the meningococcal cases (95% prediction interval: 63%-90%) expected under the Base policy if serogroup A is not replaced by remaining serogroups after elimination, and would avert 87% (77%-93%) of meningococcal cases if complete strain replacement occurs. Compared to the Base policy and at the PMC vaccine price of US$4 per dose, strategies that use PMC vaccine (i.e., Base Prime and Preventions 1 and 2) are expected to be cost saving if strain replacement occurs, and would cost US$51 (-US$236, US$490), US$188 (-US$97, US$626), and US$246 (-US$53, US$703) per DALY averted, respectively, if strain replacement does not occur. An important potential limitation of our study is the simplifying assumption that all
Ana Marli Christovam Sartori
Full Text Available ABSTRACT OBJECTIVE To describe methods and challenges faced in the health impact assessment of vaccination programs, focusing on the pneumococcal conjugate and rotavirus vaccines in Latin America and the Caribbean. METHODS For this narrative review, we searched for the terms "rotavirus", "pneumococcal", "conjugate vaccine", "vaccination", "program", and "impact" in the databases Medline and LILACS. The search was extended to the grey literature in Google Scholar. No limits were defined for publication year. Original articles on the health impact assessment of pneumococcal and rotavirus vaccination programs in Latin America and the Caribbean in English, Spanish or Portuguese were included. RESULTS We identified 207 articles. After removing duplicates and assessing eligibility, we reviewed 33 studies, 25 focusing on rotavirus and eight on pneumococcal vaccination programs. The most frequent studies were ecological, with time series analysis or comparing pre- and post-vaccination periods. The main data sources were: health information systems; population-, sentinel- or laboratory-based surveillance systems; statistics reports; and medical records from one or few health care services. Few studies used primary data. Hospitalization and death were the main outcomes assessed. CONCLUSIONS Over the last years, a significant number of health impact assessments of pneumococcal and rotavirus vaccination programs have been conducted in Latin America and the Caribbean. These studies were carried out few years after the programs were implemented, meet the basic methodological requirements and suggest positive health impact. Future assessments should consider methodological issues and challenges arisen in these first studies conducted in the region.
Embregts, Carmen W.E.; Forlenza, Maria
The limited number of oral vaccines currently approved for use in humans and veterinary species clearly illustrates that development of efficacious and safe oral vaccines has been a challenge not only for fish immunologists. The insufficient efficacy of oral vaccines is partly due to antigen breakdown in the harsh gastric environment, but also to the high tolerogenic gut environment and to inadequate vaccine design. In this review we discuss current approaches used to develop oral vaccines fo...
Intellectual property rights and challenges for development of affordable human papillomavirus, rotavirus and pneumococcal vaccines: Patent landscaping and perspectives of developing country vaccine manufacturers.
Chandrasekharan, Subhashini; Amin, Tahir; Kim, Joyce; Furrer, Eliane; Matterson, Anna-Carin; Schwalbe, Nina; Nguyen, Aurélia
The success of Gavi, the Vaccine Alliance depends on the vaccine markets providing appropriate, affordable vaccines at sufficient and reliable quantities. Gavi's current supplier base for new and underutilized vaccines, such as the human papillomavirus (HPV), rotavirus, and the pneumococcal conjugate vaccine is very small. There is growing concern that following globalization of laws on intellectual property rights (IPRs) through trade agreements, IPRs are impeding new manufacturers from entering the market with competing vaccines. This article examines the extent to which IPRs, specifically patents, can create such obstacles, in particular for developing country vaccine manufacturers (DCVMs). Through building patent landscapes in Brazil, China, and India and interviews with manufacturers and experts in the field, we found intense patenting activity for the HPV and pneumococcal vaccines that could potentially delay the entry of new manufacturers. Increased transparency around patenting of vaccine technologies, stricter patentability criteria suited for local development needs and strengthening of IPRs management capabilities where relevant, may help reduce impediments to market entry for new manufacturers and ensure a competitive supplier base for quality vaccines at sustainably low prices. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.
Choi, Yoon Hong; Chapman, Ruth; Gay, Nigel; Jit, Mark
Estimates of human papillomavirus (HPV) vaccine impact in clinical trials and modelling studies rely on DNA tests of cytology or biopsy specimens to determine the HPV type responsible for a cervical lesion. DNA of several oncogenic HPV types may be detectable in a specimen. However, only one type may be responsible for a particular cervical lesion. Misattribution of the causal HPV type for a particular abnormality may give rise to an apparent increase in disease due to non-vaccine HPV types following vaccination ("unmasking"). To investigate the existence and magnitude of unmasking, we analysed data from residual cytology and biopsy specimens in English women aged 20-64 years old using a stochastic type-specific individual-based model of HPV infection, progression and disease. The model parameters were calibrated to data on the prevalence of HPV DNA and cytological lesion of different grades, and used to assign causal HPV types to cervical lesions. The difference between the prevalence of all disease due to non-vaccine HPV types, and disease due to non-vaccine HPV types in the absence of vaccine HPV types, was then estimated.