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Sample records for acwy conjugate vaccine

  1. Safety and immunogenicity of an investigational quadrivalent meningococcal CRM(197) conjugate vaccine, MenACWY-CRM, compared with licensed vaccines in adults in Latin America.

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    Stamboulian, D; Lopardo, G; Lopez, P; Cortes-Barbosa, C; Valencia, A; Bedell, L; Karsten, A; Dull, P M

    2010-10-01

    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.

  2. Safety and immunogenicity of an investigational meningococcal ACWY conjugate vaccine (MenACWY-CRM) in healthy Indian subjects aged 2 to 75 years.

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    Lalwani, Sanjay; Agarkhedkar, Sharad; Gogtay, Nithya; Palkar, Sonali; Agarkhedkar, Shalaka; Thatte, Urmila; Vakil, Hoshang; Jonnalagedda, Rekha; Pedotti, Paola; Hoyle, Margaret; Bhusal, Chiranjiwi; Arora, Ashwani

    2015-09-01

    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.

  3. Quadrivalent meningococcal vaccination of adults: phase III comparison of an investigational conjugate vaccine, MenACWY-CRM, with the licensed vaccine, Menactra.

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    Reisinger, Keith S; Baxter, Roger; Block, Stanley L; Shah, Jina; Bedell, Lisa; Dull, Peter M

    2009-12-01

    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.

  4. Immunogenicity and safety of a novel quadrivalent meningococcal conjugate vaccine (MenACWY-CRM in healthy Korean adolescents and adults

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    Hoan Jong Lee

    2014-11-01

    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.

  5. Immunogenicity and safety of a novel quadrivalent meningococcal conjugate vaccine (MenACWY-CRM) in healthy Korean adolescents and adults.

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    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

    2014-11-01

    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.

  6. Immunogenicity and safety of a CRM-conjugated meningococcal ACWY vaccine administered concomitantly with routine vaccines starting at 2 months of age.

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    Nolan, Terry M; Nissen, Michael D; Naz, Aftab; Shepard, Julie; Bedell, Lisa; Hohenboken, Matthew; Odrljin, Tatjana; Dull, Peter M

    2014-01-01

    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.

  7. Antibody persistence 5 years after vaccination at 2 to 10 years of age with Quadrivalent MenACWY-CRM conjugate vaccine, and responses to a booster vaccination.

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    Block, Stan L; Christensen, Shane; Verma, Bikash; Xie, Fang; Keshavan, Pavitra; Dull, Peter M; Smolenov, Igor

    2015-04-27

    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.

  8. Comparative Assessment of a Single Dose and a 2-dose Vaccination Series of a Quadrivalent Meningococcal CRM-conjugate Vaccine (MenACWY-CRM) in Children 2-10 Years of Age.

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    Johnston, William; Essink, Brandon; Kirstein, Judith; Forleo-Neto, Eduardo; Percell, Sandra; Han, Linda; Keshavan, Pavitra; Smolenov, Igor

    2016-01-01

    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.

  9. Immunogenicity and reactogenicity of Infanrix™ when co-administered with meningococcal MenACWY-TT conjugate vaccine in toddlers primed with MenHibrix™ and Pediarix™.

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    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

    2015-02-11

    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

  10. Immunogenicity, Safety and Antibody Persistence of a Booster Dose of Quadrivalent Meningococcal ACWY-tetanus Toxoid Conjugate Vaccine Compared with Monovalent Meningococcal Serogroup C Vaccine Administered Four Years After Primary Vaccination Using the Same Vaccines.

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    Vesikari, Timo; Forsten, Aino; Bianco, Veronique; Van der Wielen, Marie; Miller, Jacqueline M

    2015-12-01

    We evaluated safety, immunogenicity and antibody persistence of meningococcal serogroups A, C, W and Y tetanus toxoid conjugate vaccine (MenACWY-TT) booster vaccination 4 years after priming of toddlers. This phase III, open-label, controlled study in Finland (NCT00955682) enrolled children previously randomized (3:1) at 12-23 months (NCT00474266) to receive 1 dose of MenACWY-TT or MenC conjugate vaccine (MenC-CRM197). Serum bactericidal antibody titers using rabbit (rSBA, cut-off 1:8) and human complement (hSBA, cut-off 1:8) were assessed at year 3 and 4 after priming and 1 month and 1 year after administration of a booster dose of the same vaccine given for primary vaccination. Reactogenicity and safety were assessed, and vaccination-related serious adverse events were recorded from the time of primary vaccination. Before booster (year 4), 74.1%, 40.4%, 49.3% and 58.2% of MenACWY-TT-recipients retained rSBA titers ≥1:8 for serogroups A, C, W and Y, respectively; 28.8%, 73.2%, 80.6% and 65.4% retained hSBA ≥1:8. Percentages for the MenC-CRM group were 35.6% (rSBA-MenC) and 46.9% (hSBA-MenC). After MenACWY-TT booster, ≥99.5% had rSBA ≥1:8 and hSBA ≥1:8 for each serogroup. After MenC-CRM197 booster, all children had rSBA-MenC ≥1:8 and hSBA-MenC ≥1:8. At year 5, percentages above the cut-off were ≥97.4% (rSBA) and ≥95.5% (hSBA) in MenACWY-TT-vaccinees for each serogroup. The MenACWY-TT booster dose had a clinically acceptable safety profile. No vaccine-related serious adverse events were reported. There was evidence of antibody persistence 4 years after toddlers were primed with MenACWY-TT. Booster vaccination induced robust immune responses for all serogroups with an acceptable safety profile.

  11. 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.

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    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

    2014-02-12

    The highest risk for invasive meningococcal disease (IMD) is in infants aged meningococcal conjugate vaccination has the potential to prevent IMD caused by serogroups A, C, W and Y. This phase 3b, multinational, open-label, randomized, parallel-group, multicenter study evaluated the safety of a 4-dose series of MenACWY-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 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.

  12. Antibody persistence up to 5 years after vaccination of toddlers and children between 12 months and 10 years of age with a quadrivalent meningococcal ACWY-tetanus toxoid conjugate vaccine.

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    Vesikari, Timo; Forsten, Aino; Bianco, Veronique; Van der Wielen, Marie; Miller, Jacqueline M

    2016-01-01

    We studied the persistence of serum bactericidal antibody using rabbit and human complement (rSBA/hSBA, cut-offs 1:8) 5 y after a single dose of meningococcal serogroups A, C, W, Y tetanus toxoid conjugate vaccine (MenACWY-TT) compared with age-appropriate control vaccines in toddlers and children (NCT00427908). Children were previously randomized (3:1) to receive either MenACWY-TT or control vaccine (MenC-CRM197 in 1-<2 y olds; MenACWY-polysaccharide vaccine [Men-PS] in 2-<11 y olds). Subjects with rSBA-MenC titers <1:8 at any time point were revaccinated with MenC conjugate vaccine and discontinued from the study. A repeated measurement statistical model assessed potential selection effects due to drop-outs. At year 5 in MenACWY-TT-vaccinated-toddlers for serogroups A, C, W, and Y respectively, percentages with rSBA titers ≥1:8 were 73.5%, 77.6%, 34.7%, and 42.9%, hSBA ≥1:8 were 35.6%, 91.7%, 82.6% and 80.0%. For MenC-CRM197 recipients, 63.6% had persisting rSBA-MenC titers ≥1:8 and 90.9% had hSBA-MenC ≥1:8 (not significantly different versus MenACWY-TT for either assay: exploratory analyses). In 2-<11 y olds rSBA titers ≥1:8 in MenACWY-TT-vaccinees were 90.8%, 90.8%, 78.6%, and 78.6% and 15.4%, 100%, 0.0%, 7.7% in Men-PS-vaccinees (significantly different for serogroups A, W and Y, exploratory analyses). Serogroups A, W and Y rSBA GMTs were ≥ 26-fold higher in MenACWY-TT-vaccinees. As expected, GMTs modeled at year 5 to assess the impact of subject drop out (mainly for revaccination), appeared lower for serogroup C. No vaccine-related SAEs were reported. Antibody persistence was observed for all serogroups up to 5 y after MenACWY-TT vaccination.

  13. Immunogenicity of MenACWY-CRM in Korean Military Recruits: Influence of Tetanus-Diphtheria Toxoid Vaccination on the Vaccine Response to MenACWY-CRM.

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    Kim, Han Wool; Park, In Ho; You, Sooseong; Yu, Hee Tae; Oh, In Soo; Sung, Pil Soo; Shin, Eui Cheol; Kim, Kyung Hyo

    2016-11-01

    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.

  14. 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.

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    Findlow, Jamie; Bai, Xilian; Findlow, Helen; Newton, Emma; Kaczmarski, Ed; Miller, Elizabeth; Borrow, Ray

    2015-06-26

    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

  15. 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.

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    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

    2017-08-24

    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

  16. Immunogenicity and safety of a single dose of a CRM-conjugated meningococcal ACWY vaccine in children and adolescents aged 2-18 years in Taiwan: results of an open label study.

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    Huang, Li-Min; Chiu, Nan-Chang; Yeh, Shu-Jen; Bhusal, Chiranjiwi; Arora, Ashwani Kumar

    2014-09-08

    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.

  17. 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.

    Science.gov (United States)

    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

    2015-02-11

    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.

  18. Immunogenicity and safety of a quadrivalent meningococcal serogroups A, C, W-135 and Y tetanus toxoid conjugate vaccine (MenACWY-TT) administered to adults aged 56 Years and older: results of an open-label, randomized, controlled trial.

    Science.gov (United States)

    Dbaibo, Ghassan; El-Ayoubi, Nabil; Ghanem, Soha; Hajar, Farah; Bianco, Veronique; Miller, Jacqueline M; Mesaros, Narcisa

    2013-05-01

    The burden of invasive meningococcal disease is substantial in older adults in whom the case fatality rate is high. Travelers to regions with high rates of meningococcal disease, such as Hajj pilgrims, are at increased risk of meningococcal infection, and disease transmission from travelers to their close contacts has been documented. In younger individuals, meningococcal conjugate vaccines offer advantages over polysaccharide vaccines in terms of duration of protection and boostability, and induction of herd immune effects through reductions in nasopharyngeal carriage of meningococci. To date, few data are available evaluating meningococcal conjugate vaccine use in adults >55 years of age. To evaluate the immunogenicity and safety of quadrivalent meningococcal serogroups A, C, W-135 and Y vaccine with all serogroups conjugated to tetanus toxoid (MenACWY-TT, Nimenrix™, GlaxoSmithKline, Belgium) and a licensed quadrivalent polysaccharide vaccine (MenPS, Mencevax™ GlaxoSmithKline, Belgium) in adults >55 years of age. This was a phase IIIb, open-label, randomized (3:1), controlled study conducted at one study center in Lebanon. A total of 400 healthy adults between 56 and 103 years of age without previous MenPS or tetanus toxoid vaccination within the previous 5 years or meningococcal conjugate vaccination at any time previously were included. They received a single-dose vaccination with MenACWY-TT or MenPS with blood sampling before and 1 month after vaccination. The main outcome measures were serum bactericidal activity (rabbit complement source: rSBA) vaccine response (VR) rate [rSBA titer of ≥1:32 in initially seronegative subjects (rSBA titer <1:8); ≥4-fold increase in subjects with pre-vaccination rSBA titers between 1:8 and 1:128, and ≥2-fold increase in subjects with pre-vaccination rSBA titers ≥1:128]. The percentages of subjects with rSBA titers ≥1:8 and ≥1:128 and rSBA geometric mean titers (GMTs) were assessed. Solicited adverse events

  19. MenACWY-CRM, a novel quadrivalent glycoconjugate vaccine against Neisseria meningitidis for the prevention of meningococcal infection.

    Science.gov (United States)

    Pace, David

    2009-12-01

    Invasive meningococcal disease remains a major public health concern, with infants, children younger than 4 years and adolescents bearing the majority of the global disease burden. Protecting the vulnerable individuals in these age groups through vaccination remains the most rational strategy for the prevention of meningococcal disease. The formulation of polysaccharide-protein conjugate vaccines has been a major breakthrough in vaccinology, and has extended protection against pathogenic encapsulated bacteria to younger age groups. The dramatic decline in the incidence of Neisseria meningitidis serogroup C disease, observed following the introduction of glycoconjugate meningococcal C vaccines, demonstrates that vaccination can control disease at a population level. The development of quadrivalent glycoconjugate meningococcal ACWY vaccines has broadened protection against meningococcal disease. A novel meningococcal MenACWY-CRM (Menveo) glycoconjugate vaccine, formulated by selective conjugation chemistry of intermediate-chain-length meningococcal saccharides, was immunogenic in individuals aged 2 months to 65 years. The reactogenicity of MenACWY-CRM was similar to that of other licensed meningococcal glycoconjugates, yet the vaccine has the potential to extend protection against meningococcal serogroups A, Y and W-135 to children younger than 2 years of age - a need that remains unmet.

  20. Conjugate Meningococcal Vaccines Development: GSK Biologicals Experience

    Directory of Open Access Journals (Sweden)

    Jacqueline M. Miller

    2011-01-01

    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.

  1. Conjugate Meningococcal Vaccines Development: GSK Biologicals Experience

    Science.gov (United States)

    Miller, Jacqueline M.; Mesaros, Narcisa; Van Der Wielen, Marie; Baine, Yaela

    2011-01-01

    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

  2. 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.

    Science.gov (United States)

    Gasparini, Roberto; Conversano, Michele; Bona, Gianni; Gabutti, Giovanni; Anemona, Alessandra; Dull, Peter M; Ceddia, Francesca

    2010-04-01

    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.

  3. Co-administration of a meningococcal glycoconjugate ACWY vaccine with travel vaccines: a randomized, open-label, multi-center study.

    Science.gov (United States)

    Alberer, Martin; Burchard, Gerd; Jelinek, Tomas; Reisinger, Emil; Beran, Jiri; Meyer, Seetha; Forleo-Neto, Eduardo; Gniel, Dieter; Dagnew, Alemnew F; Arora, Ashwani Kumar

    2014-01-01

    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.

  4. 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.

    Science.gov (United States)

    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

    2010-04-19

    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.

  5. Safety and Immunogenicity of a Quadrivalent Meningococcal Conjugate Vaccine and Commonly Administered Vaccines After Coadministration.

    Science.gov (United States)

    Gasparini, Roberto; Tregnaghi, Miguel; Keshavan, Pavitra; Ypma, Ellen; Han, Linda; Smolenov, Igor

    2016-01-01

    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.

  6. Safety and immunogenicity of a CRM or TT conjugated meningococcal vaccine in healthy toddlers.

    Science.gov (United States)

    Bona, Gianni; Castiglia, Paolo; Zoppi, Giorgio; de Martino, Maurizio; Tasciotti, Annaelisa; D'Agostino, Diego; Han, Linda; Smolenov, Igor

    2016-06-17

    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.

  7. 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

    NARCIS (Netherlands)

    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

    2017-01-01

    BACKGROUND: 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

  8. A phase III observer-blind randomized, controlled study to evaluate the immune response and the correlation with nasopharyngeal carriage after immunization of university students with a quadrivalent meningococcal ACWY glycoconjugate or serogroup B meningococcal vaccine.

    Science.gov (United States)

    Read, Robert C; Dull, Peter; Bai, Xilian; Nolan, Kate; Findlow, Jamie; Bazaz, Rohit; Kleinschmidt, Annett; McCarthy, Maggie; Wang, Huajun; Toneatto, Daniela; Borrow, Ray

    2017-01-11

    University students have high rates of pharyngeal carriage of Neisseria meningitidis. Interruption of carriage acquisition is an important mechanism of vaccines for inducing herd protection. 4CMenB and MenACWY-CRM vaccines have been shown to be immunogenic against meningococcal serogroups B and ACWY respectively in younger age groups, and also to elicit a modest impact on meningococcal carriage in vaccinated students. However, vaccine responses in university students and the impact of serum bactericidal antibody (SBA) titers on meningococcal carriage are undetermined. Immunogenicity of two 4CMenB doses or one MenACWY-CRM dose was measured in university students at Months 2, 4, 6 and 12 post-first vaccination. Immunogenicity of one MenACWY-CRM dose in students with previous meningococcal serogroup C conjugate vaccination was also assessed. Immune responses were measured with an SBA assay using human complement (hSBA) against three reference strains for serogroup B and against one strain for each for serogroups C and Y. Correlations between hSBA titers and meningococcal carriage were analyzed. All subjects demonstrated robust functional antibody responses to both vaccines at Month 2 and a high proportion maintained protective hSBA titers up to Month 12. At baseline, carriage of disease-associated serogroup B strains and serogroups C and Y were higher in subjects with already-protective hSBA titers. Post-vaccination, while both 4CMenB and MenACWY-CRM elicited robust immunogenicity in students, significant correlations between post-vaccination hSBA titers and carriage of disease-associated serogroups were not observed. 4CMenB and MenACWY-CRM were both highly immunogenic. There was no correlation between carriage and post-vaccination hSBA titers. Copyright © 2016. Published by Elsevier Ltd.

  9. Use of MenACWY-CRM vaccine in children aged 2 through 23 months at increased risk for meningococcal disease: recommendations of the Advisory Committee on Immunization Practices, 2013.

    Science.gov (United States)

    MacNeil, Jessica R; Rubin, Lorry; McNamara, Lucy; Briere, Elizabeth C; Clark, Thomas A; Cohn, Amanda C

    2014-06-20

    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.

  10. 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.

    Science.gov (United States)

    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

    2015-08-01

    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.

  11. Effect of a quadrivalent meningococcal ACWY glycoconjugate or a serogroup B meningococcal vaccine on meningococcal carriage: an observer-blind, phase 3 randomised clinical trial.

    Science.gov (United States)

    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

    2014-12-13

    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

  12. Emergency Meningococcal ACWY Vaccination Program for Teenagers to Control Group W Meningococcal Disease, England, 2015-2016.

    Science.gov (United States)

    Campbell, Helen; Edelstein, Michael; Andrews, Nick; Borrow, Ray; Ramsay, Mary; Ladhani, Shamez

    2017-07-01

    During the first 12 months of an emergency meningococcal ACWY vaccination program for teenagers in England, coverage among persons who left school in 2015, the first cohort to be vaccinated, was 36.6%. There were 69% fewer group W meningococcal cases than predicted by trend analysis and no cases in vaccinated teenagers.

  13. Safety and immunogenicity of typhoid fever and yellow fever vaccines when administered concomitantly with quadrivalent meningococcal ACWY glycoconjugate vaccine in healthy adults.

    Science.gov (United States)

    Alberer, Martin; Burchard, Gerd; Jelinek, Tomas; Reisinger, Emil; Beran, Jiri; Hlavata, Lucie Cerna; Forleo-Neto, Eduardo; Dagnew, Alemnew F; Arora, Ashwani K

    2015-01-01

    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

  14. Immunogenicity and safety of a quadrivalent meningococcal polysaccharide CRM conjugate vaccine in infants and toddlers.

    Science.gov (United States)

    Tregnaghi, Miguel; Lopez, Pio; Stamboulian, Daniel; Graña, Gabriela; Odrljin, Tatjana; Bedell, Lisa; Dull, Peter M

    2014-09-01

    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.

  15. Immunogenicity and safety of concomitant administration of a combined hepatitis A/B vaccine and a quadrivalent meningococcal conjugate vaccine in healthy adults.

    Science.gov (United States)

    Alberer, Martin; Burchard, Gerd; Jelinek, Tomas; Reisinger, Emil C; Meyer, Seetha; Forleo-Neto, Eduardo; Dagnew, Alemnew F; Arora, Ashwani Kumar

    2015-01-01

    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

  16. The B-cell response to a primary and booster course of MenACWY-CRM₁₉₇ vaccine administered at 2, 4 and 12 months of age.

    Science.gov (United States)

    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

    2013-05-07

    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.

  17. Safety and Immunogenicity of the Quadrivalent Meningococcal Serogroups A, C, W and Y Tetanus Toxoid Conjugate Vaccine Coadministered With Routine Childhood Vaccines in European Infants: An Open, Randomized Trial.

    Science.gov (United States)

    Merino Arribas, Jose Manuel; Carmona Martínez, Alfonso; Horn, Michael; Perez Porcuna, Xavier Maria; Otero Reigada, Maria Del Carmen; Marès Bermúdez, Josep; Centeno Malfaz, Fernando; Miranda, Mariano; Mendez, Maria; Garcia Cabezas, Miguel Angel; Wittermann, Christoph; Bleckmann, Gerhard; Fischbach, Thomas; Kolhe, Devayani; van der Wielen, Marie; Baine, Yaela

    2017-04-01

    This was the first study evaluating the immunogenicity and safety of the quadrivalent meningococcal tetanus toxoid conjugate vaccine (MenACWY-TT) coadministered with routine childhood vaccines in young infants. In this open, randomized, controlled, phase III study (NCT01144663), 2095 infants (ages 6-12 weeks) were randomized (1:1:1:1) into 4 groups to receive MenACWY-TT at 2, 3, 4 and 12 months of age, or MenACWY-TT, MenC-cross-reactive material (CRM197) or MenC-TT at 2, 4 and 12 months of age. All participants received PHiD-CV and DTPa-HBV-IPV/Hib at 2, 3, 4 and 12 months of age. Immune responses were measured by serum bactericidal activity assays using rabbit (rSBA) and human (hSBA) complement. Solicited and unsolicited symptoms were recorded during 8 and 31 days post-vaccination, respectively, and serious adverse events throughout the study. Noninferiority of immune responses to MenC induced by 2 or 3 doses of MenACWY-TT versus 2 doses of MenC-TT or MenC-CRM197 was demonstrated. Predefined criteria for the immunogenicity of MenACWY-TT to MenA, MenW and MenY were met. One month after 2 or 3 primary MenACWY-TT doses, ≥93.1% and ≥88.5% of infants had rSBA and hSBA titers ≥1:8 for all serogroups. The robust increases in rSBA and hSBA titers observed for all vaccine serogroups postbooster vaccination suggested that MenACWY-TT induced immune memory. MenACWY-TT coadministered with childhood vaccines had a clinically acceptable safety profile. This study supports the coadministration of MenACWY-TT with routine childhood vaccines as 2 or 3 primary doses during infancy followed by a booster dose in the second year of life.

  18. Safety of Quadrivalent Meningococcal Conjugate Vaccine in Children 2-10 Years.

    Science.gov (United States)

    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

    2017-11-01

    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.

  19. Meningococcal Serogroup A, C, W135 and Y Conjugated Vaccine: A Cost-Effectiveness Analysis in the Netherlands

    Science.gov (United States)

    van der Ende, Arie; Westra, Tjalke A.; Postma, Maarten J.

    2013-01-01

    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. PMID:23741448

  20. 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

    Science.gov (United States)

    Vesikari, Timo; Forstén, Aino; Boutriau, Dominique; Bianco, Véronique; Van der Wielen, Marie; Miller, Jacqueline M.

    2012-01-01

    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

  1. Protein carriers of conjugate vaccines

    Science.gov (United States)

    Pichichero, Michael E

    2013-01-01

    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

  2. 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.

    Science.gov (United States)

    Lupisan, Socorro; Limkittikul, Kriengsak; Sosa, Nestor; Chanthavanich, Pornthep; Bianco, Véronique; Baine, Yaela; Van der Wielen, Marie; Miller, Jacqueline M

    2013-10-01

    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.

  3. Use of MenACWY-CRM in adolescents in the United States.

    Science.gov (United States)

    Black, Steven; Block, Stan L

    2013-03-01

    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.

  4. Critical appraisal of a quadrivalent CRM(197) conjugate vaccine against meningococcal serogroups A, C W-135 and Y (Menveo) in the context of treatment and prevention of invasive disease.

    Science.gov (United States)

    Bröker, Michael; Cooper, Brian; Detora, Lisa M; Stoddard, Jeffrey J

    2011-01-01

    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.

  5. Critical appraisal of a quadrivalent CRM197 conjugate vaccine against meningococcal serogroups A, C W-135 and Y (Menveo®) in the context of treatment and prevention of invasive disease

    Science.gov (United States)

    Bröker, Michael; Cooper, Brian; DeTora, Lisa M; Stoddard, Jeffrey J

    2011-01-01

    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

  6. The tetravalent meningococcal serogroups A, C, W-135, and Y tetanus toxoid conjugate vaccine is immunogenic with a clinically acceptable safety profile in subjects previously vaccinated with a tetravalent polysaccharide vaccine.

    Science.gov (United States)

    Dbaibo, Ghassan; Van der Wielen, Marie; Reda, Mariam; Medlej, Fouad; Tabet, Carelle; Boutriau, Dominique; Sumbul, Anne; Anis, Sameh; Miller, Jacqueline M

    2012-08-01

    The immunogenicity and safety of the tetravalent meningococcal serogroups A, C, W-135, and Y tetanus toxoid conjugate vaccine (MenACWY-TT) were evaluated in subjects previously vaccinated with a tetravalent meningococcal polysaccharide vaccine and in subjects without previous meningococcal vaccination. In this phase II, open, controlled study (NCT00661557), healthy subjects aged 4.5-34 years received one dose of MenACWY-TT at month 0. Subjects in the MPS group (n=192) had received polysaccharide vaccine in a study conducted 30-42 months earlier; age-matched subjects in the noMPS control group (n=79) had received no meningococcal vaccination within the past 10 years. Serum bactericidal activity using rabbit complement (rSBA) was measured at month 0 and month 1. At month 1, ≥97.0% of subjects had rSBA titers ≥1:128. Post-vaccination rSBA geometric mean titers (GMTs) were ≥3.9-fold higher than pre-vaccination in both treatment groups. Exploratory analyses showed no statistically significant differences between groups in percentages of subjects with rSBA titers ≥1:8 and ≥1:128, but significantly lower rSBA GMTs and vaccine response rates for each serogroup in the MPS versus the noMPS group. MenACWY-TT had an acceptable safety profile in both groups. These results suggest that MenACWY-TT could be used in vaccination programs irrespective of the pre-vaccination status with polysaccharide vaccine. Copyright © 2012 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  7. Critical appraisal of a quadrivalent CRM197 conjugate vaccine against meningococcal serogroups A, C W-135 and Y (Menveo® in the context of treatment and prevention of invasive disease

    Directory of Open Access Journals (Sweden)

    Bröker M

    2011-07-01

    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

  8. 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.

    Science.gov (United States)

    Voysey, Merryn; Sadarangani, Manish; Clutterbuck, Elizabeth; Bolgiano, Barbara; Pollard, Andrew J

    2016-07-25

    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.

  9. Safety and immunogenicity of a novel quadrivalent meningococcal CRM-conjugate vaccine given concomitantly with routine vaccinations in infants.

    Science.gov (United States)

    Klein, Nicola P; Reisinger, Keith S; Johnston, William; Odrljin, Tatjana; Gill, Christopher J; Bedell, Lisa; Dull, Peter

    2012-01-01

    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.

  10. Persistence of the immune response after MenACWY-CRM vaccination and response to a booster dose, in adolescents, children and infants.

    Science.gov (United States)

    Baxter, Roger; Keshavan, Pavitra; Welsch, Jo Anne; Han, Linda; Smolenov, Igor

    2016-05-03

    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.

  11. Meningococcal conjugate vaccines: optimizing global impact

    Directory of Open Access Journals (Sweden)

    Terranella A

    2011-09-01

    Full Text Available Andrew Terranella1,2, Amanda Cohn2, Thomas Clark2 1Epidemic Intelligence Service, Division of Applied Sciences, Scientific Education and Professional Development Program Office, 2Meningitis and Vaccine Preventable Diseases Branch, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA Abstract: Meningococcal conjugate vaccines have several advantages over polysaccharide vaccines, including the ability to induce greater antibody persistence, avidity, immunologic memory, and herd immunity. Since 1999, meningococcal conjugate vaccine programs have been established across the globe. Many of these vaccination programs have resulted in significant decline in meningococcal disease in several countries. Recent introduction of serogroup A conjugate vaccine in Africa offers the potential to eliminate meningococcal disease as a public health problem in Africa. However, the duration of immune response and the development of widespread herd immunity in the population remain important questions for meningococcal vaccine programs. Because of the unique epidemiology of meningococcal disease around the world, the optimal vaccination strategy for long-term disease prevention will vary by country. Keywords: conjugate vaccine, meningitis, meningococcal vaccine, meningococcal disease

  12. Middle school vaccination requirements and adolescent vaccination coverage.

    Science.gov (United States)

    Bugenske, Erin; Stokley, Shannon; Kennedy, Allison; Dorell, Christina

    2012-06-01

    To determine if middle school vaccination requirements are associated with higher coverage for adolescent vaccines. School entry requirements for receipt of vaccination for school entry or education of parents for 3 vaccines recommended for adolescents: tetanus/diphtheria-containing (Td) or tetanus/diphtheria/acellular pertussis (TdaP), meningococcal conjugate (MenACWY), and human papillomavirus (HPV) vaccines in place for the 2008-2009 school year were reviewed for the 50 states and the District of Columbia. Vaccination coverage levels for adolescents 13 to 17 years of age by state requirement status and change in coverage from 2008 to 2009 were assessed by using the 2008-2009 National Immunization Survey-Teen. For the 2008-2009 school year, 32 states had requirements for Td/TdaP (14 specifically requiring TdaP) and none required education; 3 states required MenACWY vaccine and 10 others required education; and 1 state required HPV vaccine and 5 required education. Compared with states with no requirements, vaccination requirements were associated with significantly higher coverage for MenACWY (71% vs 53%, P vaccines. No association was found between education-only requirements and coverage levels for MenACWY and HPV vaccines. States with new 2008-2009 vaccination requirements (n = 6, P = .04) and states with preexisting vaccination requirements (n = 26, P = .02) for Td/TdaP experienced a significant increase in TdaP coverage over states with no requirements. Middle school vaccination requirements are associated with higher coverage for Td/TdaP and MenACWY vaccines, whereas education-only requirements do not appear to increase coverage levels for MenACWY or HPV vaccines. The impact on coverage should continue to be monitored as more states adopt requirements.

  13. Immunogenicity and safety of a new meningococcal A conjugate vaccine in Indian children aged 2-10 years: a phase II/III double-blind randomized controlled trial.

    Science.gov (United States)

    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

    2012-10-05

    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.

  14. Serogroup A meningococcal conjugate vaccines in Africa.

    Science.gov (United States)

    Kristiansen, Paul A; Jørgensen, Hannah J; Caugant, Dominique A

    2015-01-01

    Serogroup A meningococcal epidemics have been a recurrent public health problem, especially in resource-poor countries of Africa. Recently, the administration in mass vaccination campaigns of a single dose of the monovalent meningococcal conjugate vaccine, MenAfriVac, to the 1-29 year-old population of sub-Saharan Africa has prevented epidemics of meningitis caused by serogroup A Neisseria meningitidis. This strategy has also been shown to provide herd protection of the non-vaccinated population. Development of meningococcal conjugate vaccines covering other serogroups and enhanced use of the pneumococcal and Haemophilus influenzae type b conjugate vaccines must be pursued to fully control bacterial meningitis in sub-Saharan Africa.

  15. 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.

    Science.gov (United States)

    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

    2013-07-01

    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.

  16. Vaccinations for Adults with HIV Infection

    Science.gov (United States)

    ... 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 ...

  17. Determinants of pneumococcal conjugate vaccine uptake among ...

    African Journals Online (AJOL)

    Subjects: The respondents were the parents/guardians of children less than two years of age attending immunisation services at KNH and those admitted in the peadiatric wards with pneumonia. Results: The study established that the determinants of uptake of Pneumococcal Conjugate Vaccine are age(OR 5.8, CI 1.4-23.4, ...

  18. Pneumococcal Conjugate Vaccine (PCV13): What You Need to Know

    Science.gov (United States)

    ... drugs. This makes prevention of the disease, through vaccination, even more important. 2 PCV13 vaccine Pneumococcal conjugate vaccine (called PCV13) protects against 13 types of pneumococcal bacteria. PCV13 is routinely given to ...

  19. Pneumococcal conjugate vaccine (PCV13) - What you need to know

    Science.gov (United States)

    ... drugs. This makes prevention of the disease, through vaccination, even more important. 2. PCV13 vaccine Pneumococcal conjugate vaccine (called PCV13) protects against 13 types of pneumococcal bacteria. PCV13 is routinely given to ...

  20. Factors contributing to the immunogenicity of meningococcal conjugate vaccines

    Science.gov (United States)

    Bröker, Michael; Berti, Francesco; Costantino, Paolo

    2016-01-01

    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

  1. Meningococcal Vaccines: What You Need to Know

    Science.gov (United States)

    ... 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 ...

  2. Protein carriers of conjugate vaccines: Characteristics, development, and clinical trials

    OpenAIRE

    Pichichero, Michael E

    2013-01-01

    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 characterist...

  3. Protein carriers of conjugate vaccines: characteristics, development, and clinical trials.

    Science.gov (United States)

    Pichichero, Michael E

    2013-12-01

    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.

  4. Progress towards meningitis prevention in the conjugate vaccines era

    Directory of Open Access Journals (Sweden)

    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.

  5. Conjugate Haemophilus influenzae type b vaccines for sickle cell disease.

    Science.gov (United States)

    Allali, Slimane; Chalumeau, Martin; Launay, Odile; Ballas, Samir K; de Montalembert, Mariane

    2016-02-16

    People affected with sickle cell disease are at high risk of infection from Haemophilus influenzae type b. Before the implementation of Haemophilus influenzae type b conjugate vaccination in high-income countries, this was responsible for a high mortality rate in children under five years of age. In African countries, where coverage of this vaccination is still extremely low, Haemophilus influenzae type b remains one of the most common cause of bacteraemias in children with sickle cell disease. The increased uptake of this conjugate vaccination may substantially improve the survival of children with sickle cell disease. The primary objective was to determine whether Haemophilus influenzae type b conjugate vaccines reduce mortality and morbidity in children and adults with sickle cell disease.The secondary objectives were to assess the following in children and adults with sickle cell disease: the immunogenicity of Haemophilus influenzae type b conjugate vaccines; the safety of these vaccines; and any variation in effect according to type of vaccine, mode of administration (separately or in combination with other vaccines), number of doses, and age at first dose. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also contacted relevant pharmaceutical companies to identify unpublished trials.Date of last search: 23 November 2015. All randomised and quasi-randomised controlled trials comparing Haemophilus influenzae type b conjugate vaccines with placebo or no treatment, or comparing different types of Haemophilus influenzae type b conjugate vaccines in people with sickle cell disease. No trials of Haemophilus influenzae type b conjugate vaccines in people with sickle cell disease were found. There is an absence of evidence from randomised controlled trials relating to the subject of this review. There has

  6. Vaccination of risk groups in England using the 13 valent pneumococcal conjugate vaccine : economic analysis

    NARCIS (Netherlands)

    Rozenbaum, Mark H.; van Hoek, Albert Jan; Fleming, Douglas; Trotter, Caroline L.; Miller, Elizabeth; Edmunds, W. John

    2012-01-01

    Objective To estimate the cost effectiveness of vaccinating people with high risk conditions against invasive pneumococcal disease using the 13 valent pneumococcal conjugate vaccine. Design Economic evaluation using a cohort model from the perspective of healthcare providers. Setting England.

  7. Neisseria meningitidis Group A IgG1 and IgG2 Subclass Immune Response in African Children Aged 12–23 Months Following Meningococcal Vaccination

    Science.gov (United States)

    Holme, Daniel; Findlow, Helen; Sow, Samba O.; Idoko, Olubukola T.; Preziosi, Marie-Pierre; Carlone, George; Plikaytis, Brian D.; Borrow, Ray

    2015-01-01

    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

  8. Long-term immune responses to pneumococcal conjugate vaccines in children previously vaccinated with 7-valent pneumococcal conjugate vaccine.

    Science.gov (United States)

    Klein, Nicola P; Ensor, Kathy; Jouve, Sylvie; Northington, Robert; Moscariello, Michele; McGovern, Paul C

    2013-09-01

    Seven-valent pneumococcal conjugate vaccine (PCV7) has reduced incidence of vaccine-serotype pneumococcal diseases. Using a single dose of 13-valent pneumoccal conjugate vaccine (PCV13), we evaluated late immune responses 10 years after vaccination with PCV7 in infancy, compared with a PCV7-naïve cohort. In this open-label study, we administered 1 dose of PCV13 to children aged 11-14 years who had previously received PCV7 (PCV7/PCV13) or meningococcal group C conjugate vaccine (MnCC/PCV13) during infancy. We evaluated serotype-specific immunoglobulin G concentrations and opsonophagocytic activity prevaccination and 1 week and 1 month postvaccination. We recorded local reactions and systemic events for 4 days postvaccination and adverse events for 6 months. Seventy-four subjects received PCV13 (PCV7/PCV13, n = 38; MnCC/PCV13, n = 36). Prevaccination with PCV13, >62.9% of subjects had immunoglobulin G concentrations ≥0.35 µg/mL for all serotypes except serotype 4 (28-29%); proportions increased at 1 month postvaccination to 100% for all serotypes except serotypes 3 (PCV7/PCV13, 94.7%; MnCC/PCV13, 97.0%) and 14 (MnCC/PCV13, 97.1%). Immunoglobulin G and opsonophagocytic activity concentrations for the 7 common and 6 additional serotypes were similar in both groups prevaccination and increased in both groups from prevaccination to 1 week and 1 month postvaccination. Local reactions and fever were mild or moderate; no serious adverse events were reported. Late immune responses after a single dose of PCV13 were similar in children aged 11-14 years regardless of previous vaccination with PCV7 or MnCC. PCV13 was immunogenic, safe and well tolerated.

  9. Evaluation of Haemophilus influenzae Type B Conjugate Vaccine (Meningococcal Protein Conjugate in Canadian Infants

    Directory of Open Access Journals (Sweden)

    David W Scheifele

    1994-01-01

    Full Text Available Objective: To assess adverse effects and immune responses with a three-dose series of Haemophilus influenzae type b meningococcal protein conjugate (PedvaxHIB or Hib.OMP vaccine, including any immunological response alterations from concurrent administration with routine vaccines for infants.

  10. Invasive pneumococcal infection despite 7-valent conjugated vaccine

    Directory of Open Access Journals (Sweden)

    Sebastien Joye

    2013-03-01

    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.

  11. Optimal serotype compositions for Pneumococcal conjugate vaccination under serotype replacement.

    Science.gov (United States)

    Nurhonen, Markku; Auranen, Kari

    2014-02-01

    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

  12. Optimal Serotype Compositions for Pneumococcal Conjugate Vaccination under Serotype Replacement

    Science.gov (United States)

    Nurhonen, Markku; Auranen, Kari

    2014-01-01

    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 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 new serotypes in the vaccine (e.g. 22 and 9N). PMID:24550722

  13. Immunological characterization of conjugated Haemophilus influenzae type b vaccine failure in infants

    NARCIS (Netherlands)

    Breukels, M. A.; Spanjaard, L.; Sanders, L. A.; Rijkers, G. T.

    2001-01-01

    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

  14. [Pneumococcal vaccination: conjugated vaccine induces herd immunity and reduces antibiotic resistance].

    Science.gov (United States)

    Pletz, M W; Maus, U; Hohlfeld, J M; Lode, H; Welte, T

    2008-02-01

    Pneumococcal infections (pneumonia, otitis media, sinusitis, meningitis) are common and usually involve toddlers and the elderly. Currently, two pneumococcal vaccines are in clinical use. The older vaccine consists of pure capsular polysaccharides from 23 pneumococcal serotypes and induces only a limited B-cell response because polysaccharides are poor antigens that stimulate mainly B-cells. In 2000, a vaccination program with a novel 7-valent pneumococcal conjugate vaccine was launched in the U.S. The conjugation of capsular polysaccharides with a highly immunogenic diphtheria toxoid protein induces both a T cell and B cell response that results in specific humoral and mucosal immunity. Since children are the main reservoir of pneumococci, the 7-valent conjugate vaccine seems to eradicate the respective pneumococcal serotypes within the population, as demonstrated by recent US data. Pronounced herd immunity resulted in a decrease in invasive pneumococcal diseases in vaccinees and non-vaccinees as well as in a reduction of antibiotic resistance rates. However, recent data suggest a replacement of vaccine-serotypes by non-vaccine serotypes, which conquer the ecological niche created by the vaccine. In order to encounter this problem a 13-valent conjugated vaccine is currently under development.

  15. New pneumococcal conjugate vaccine introductions in four sub ...

    African Journals Online (AJOL)

    Background: Pneumonia is a main cause of under-five mortality in low-income settings. The pneumococcal conjugate vaccine (PCV) has been introduced in many countries as a tool in the disease's prevention. Although PCV's effectiveness has been established, less is known about the effects of introducing additional ...

  16. The role of economic evaluation in vaccine decision making : Focus on meningococcal group C conjugate vaccine

    NARCIS (Netherlands)

    Welte, R.; Trotter, C.L.; Edmunds, W.J.; Postma, Maarten; Beutels, P.H.

    2005-01-01

    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

  17. Safety of a new conjugate meningococcal C vaccine in infants.

    Science.gov (United States)

    Lakshman, R; Jones, I; Walker, D; McMurtrie, K; Shaw, L; Race, G; Choo, S; Danzig, L; Oster, P; Finn, A

    2001-11-01

    Group C conjugate meningococcal vaccines (Men C) were introduced into the UK primary immunisation schedule in November 1999. There has been extensive professional and public interest in their efficacy and safety. To determine the occurrence of at least one uncommon adverse event in infants related to the administration of the Chiron Men C vaccine. A total of 2796 infants aged approximately 2 months were recruited into the study from areas in and around Sheffield and from Scotland. They were vaccinated with the Chiron Men C vaccine at 2, 3, and 4 months along with routine immunisations. Data on adverse events occurring one month after each dose were collected actively and prospectively and reviewed for possible relation to the vaccine. There were no deaths. There were no serious adverse events considered definitely or probably caused by the vaccine. Four infants developed serious adverse events (hypotonia, screaming syndrome, maculopapular rash, and agitation, respectively) that were considered possibly related to the vaccine. All recovered completely. Adverse events were seen in 1804 children but were considered possibly related to the vaccine in only 49 (1.8%). On subsequent immunisation there were no recurrences of adverse events considered to be possibly related to the vaccine.

  18. Meningococcal vaccines and herd immunity: lessons learned from serogroup C conjugate vaccination programmes

    OpenAIRE

    Trotter, Caroline L; Maiden, Martin C J

    2009-01-01

    Effective vaccines provide direct protection to immunised individuals, but may also provide benefits to unvaccinated individuals by reducing transmission and hence lowering the risk of infection. Such herd immunity effects have been demonstrated following the introduction of meningococcal serogroup C conjugate (MCC) vaccines, with reductions in disease attack rates in unimmunised individuals and significantly lower serogroup C carriage attributable to the vaccine introduction. In the UK targe...

  19. Effectiveness of pneumococcal conjugate vaccine and rotavirus ...

    African Journals Online (AJOL)

    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 ...

  20. Conjugation, characterization and toxicity of lipophosphoglycan-polyacrylic acid conjugate for vaccination against leishmaniasis.

    Science.gov (United States)

    Topuzogullari, Murat; Cakir Koc, Rabia; Dincer Isoglu, Sevil; Bagirova, Melahat; Akdeste, Zeynep; Elcicek, Serhat; Oztel, Olga N; Yesilkir Baydar, Serap; Canim Ates, Sezen; Allahverdiyev, Adil M

    2013-06-03

    Research on the conjugates of synthetic polyelectrolytes with antigenic molecules, such as proteins, peptides, or carbohydrates, is an attractive area due to their highly immunogenic character in comparison to classical adjuvants. For example, polyacrylic acid (PAA) is a weak polyelectrolyte and has been used in several biomedical applications such as immunological studies, drug delivery, and enzyme immobilization. However, to our knowledge, there are no studies that document immune-stimulant properties of PAA in Leishmania infection. Therefore, we aimed to develop a potential vaccine candidate against leishmaniasis by covalently conjugating PAA with an immunologically vital molecule of lipophosphoglycan (LPG) found in Leishmania parasites. In the study, LPG and PAA were conjugated by a multi-step procedure, and final products were analyzed with GPC and MALDI-TOF MS techniques. In cytotoxicity experiments, LPG-PAA conjugates did not indicate toxic effects on L929 and J774 murine macrophage cells. We assume that LPG-PAA conjugate can be a potential vaccine candidate, and will be immunologically characterized in further studies to prove its potential.

  1. Decreased immune response to pneumococcal conjugate vaccine after 23-valent pneumococcal polysaccharide vaccine in children.

    Science.gov (United States)

    Sigurdardottir, Sigurveig Th; Center, Kimberly J; Davidsdottir, Katrin; Arason, Vilhjalmur A; Hjalmarsson, Bjorn; Elisdottir, Ragnheidur; Ingolfsdottir, Gunnhildur; Northington, Robert; Scott, Daniel A; Jonsdottir, Ingileif

    2014-01-09

    Pneumococcal polysaccharide vaccine (PPV) is used in children at high risk of IPD. PPV is generally not considered to induce immunologic memory, whereas pneumococcal conjugate vaccines (PCVs) elicit protective antibody responses in infants and induce immunologic memory. Little is known about the characteristics of immune responses to PCV in children who previously received PCV and PPV in series. To characterize immune responses to 13-valent pneumococcal CRM197 conjugate vaccine (PCV13; serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) in children vaccinated in infancy with 9-valent pneumococcal-meningococcal C-CRM197 conjugate combination vaccine (PCV9-MnCC), followed by a toddler dose of PCV9-MnCC or 23-valent pneumococcal polysaccharide vaccine (PPV23). Children (n=89) who received PCV9-MnCC in infancy and PPV23 or PCV9-MnCC at age 12 months in a previous (2002-2003) study were vaccinated at age 7.5 years with PCV13; groups PPV23/PCV13 (n=50) and PCV9/PCV13 (n=39). Immunoglobulin (Ig)G antibodies, avidity, and opsonophagocytic activity (OPA) were measured before and at 1 and 4 weeks postvaccination. One week postvaccination, IgG levels increased significantly for all serotypes in both groups, and >97% of vaccinees achieved IgG ≥0.35μg/ml 4 weeks after PCV13 vaccination. The PCV9/PCV13 group had higher IgG responses compared with the PPV23/PCV13 group. The upper limits of the 95% confidence intervals of the PPV23/PCV13:PCV9/PCV13 IgG geometric mean concentration ratios were vaccination of toddlers may compromise subsequent responses to pneumococcal conjugate vaccines. The clinical relevance of this finding is unclear. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Safety and immunogenicity of meningococcal A and C polysaccharide conjugate vaccine in adults.

    OpenAIRE

    Anderson, E L; Bowers, T; Mink, C M; Kennedy, D J; Belshe, R B; Harakeh, H; Pais, L; Holder, P; Carlone, G M

    1994-01-01

    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, ...

  3. VACCINATION OF PREMATURE INFANTS AND CHILDREN WITH CONGENITAL HEART DISEASE IN IRKUTSK USING CONJUGATED PNEUMOCOCCAL VACCINES

    Directory of Open Access Journals (Sweden)

    S. V. Il'ina

    2013-01-01

    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. 

  4. Cross Reactive Material 197 glycoconjugate vaccines contain privileged conjugation sites.

    Science.gov (United States)

    Möginger, Uwe; Resemann, Anja; Martin, Christopher E; Parameswarappa, Sharavathi; Govindan, Subramanian; Wamhoff, Eike-Christian; Broecker, Felix; Suckau, Detlev; Pereira, Claney Lebev; Anish, Chakkumkal; Seeberger, Peter H; Kolarich, Daniel

    2016-02-04

    Production of glycoconjugate vaccines involves the chemical conjugation of glycans to an immunogenic carrier protein such as Cross-Reactive-Material-197 (CRM197). Instead of using glycans from natural sources recent vaccine development has been focusing on the use of synthetically defined minimal epitopes. While the glycan is structurally defined, the attachment sites on the protein are not. Fully characterized conjugates and batch-to-batch comparisons are the key to eventually create completely defined conjugates. A variety of glycoconjugates consisting of CRM197 and synthetic oligosaccharide epitopes was characterised using mass spectrometry techniques. The primary structure was assessed by combining intact protein MALDI-TOF-MS, LC-MALDI-TOF-MS middle-down and LC-ESI-MS bottom-up approaches. The middle-down approach on CNBr cleaved glycopeptides provided almost complete sequence coverage, facilitating rapid batch-to-batch comparisons, resolving glycan loading and identification of side products. Regions close to the N- and C-termini were most efficiently conjugated.

  5. Persistence of immune responses after a single dose of Novartis meningococcal serogroup A, C, W-135 and Y CRM-197 conjugate vaccine (Menveo®) or Menactra® among healthy adolescents.

    Science.gov (United States)

    Gill, Christopher J; Baxter, Roger; Anemona, Alessandra; Ciavarro, Giuseppe; Dull, Peter

    2010-11-01

    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.

  6. Humoral response to conjugate pneumococcal vaccine in paediatric oncology patients.

    Science.gov (United States)

    Cheng, Frankie Wai Tsoi; Ip, Margaret; Chu, Yvonne Yuen Ling; Lin, Zheng; Lee, Vincent; Shing, Ming Kong; Leung, Wing Kwan; Yuen, Patrick Man Pan; Li, Chi Kong

    2012-04-01

    Pneumococcal conjugate vaccine (PCV) is an effective way to prevent invasive pneumococcal diseases in high risk populations. The efficacy of this vaccine in paediatric oncology patients remains unknown. The authors evaluated the antibody response to seven pneumococcal serotypes in paediatric oncology patients given two doses of heptavalent PCV (PCV-7). Forty-four patients (20 males; 24 females) with median age 9.5 years were studied. After two doses of PCV-7, 86-100% of patients had protective antibody titres against the seven vaccine serotypes. Increases in geometric mean antibody concentrations ranged from 3.8-fold for serotype 19F to 85.8-fold for serotype 14. There was no documented invasive pneumococcal disease in our cohort during the study period. PCV can elicit protective antipneumococcal antibody responses in paediatric oncology patients.

  7. Self-Adjuvanting Glycopeptide Conjugate Vaccine against Disseminated Candidiasis

    Science.gov (United States)

    Xin, Hong; Cartmell, Jonathan; Bailey, Justin J.; Dziadek, Sebastian; Bundle, David R.; Cutler, Jim E.

    2012-01-01

    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

  8. Cost effectiveness of pneumococcal conjugate vaccination against acute otitis media in children: a review.

    NARCIS (Netherlands)

    Boonacker, C.W.; Broos, P.H.; Sanders, E.A.; Schilder, A.G.M.; Rovers, M.M.

    2011-01-01

    While pneumococcal conjugate vaccines have shown to be highly effective against invasive pneumococcal disease, their potential effectiveness against acute otitis media (AOM) might become a major economic driver for implementing these vaccines in national immunization programmes. However, the

  9. Herd immunity and pneumococcal conjugate vaccine: a quantitative model.

    Science.gov (United States)

    Haber, Michael; Barskey, Albert; Baughman, Wendy; Barker, Lawrence; Whitney, Cynthia G; Shaw, Kate M; Orenstein, Walter; Stephens, David S

    2007-07-20

    Invasive pneumococcal disease in older children and adults declined markedly after introduction in 2000 of the pneumococcal conjugate vaccine for young children. An empirical quantitative model was developed to estimate the herd (indirect) effects on the incidence of invasive disease among persons >or=5 years of age induced by vaccination of young children with 1, 2, or >or=3 doses of the pneumococcal conjugate vaccine, Prevnar (PCV7), containing serotypes 4, 6B, 9V, 14, 18C, 19F and 23F. From 1994 to 2003, cases of invasive pneumococcal disease were prospectively identified in Georgia Health District-3 (eight metropolitan Atlanta counties) by Active Bacterial Core surveillance (ABCs). From 2000 to 2003, vaccine coverage levels of PCV7 for children aged 19-35 months in Fulton and DeKalb counties (of Atlanta) were estimated from the National Immunization Survey (NIS). Based on incidence data and the estimated average number of doses received by 15 months of age, a Poisson regression model was fit, describing the trend in invasive pneumococcal disease in groups not targeted for vaccination (i.e., adults and older children) before and after the introduction of PCV7. Highly significant declines in all the serotypes contained in PCV7 in all unvaccinated populations (5-19, 20-39, 40-64, and >64 years) from 2000 to 2003 were found under the model. No significant change in incidence was seen from 1994 to 1999, indicating rates were stable prior to vaccine introduction. Among unvaccinated persons 5+ years of age, the modeled incidence of disease caused by PCV7 serotypes as a group dropped 38.4%, 62.0%, and 76.6% for 1, 2, and 3 doses, respectively, received on average by the population of children by the time they are 15 months of age. Incidence of serotypes 14 and 23F had consistent significant declines in all unvaccinated age groups. In contrast, the herd immunity effects on vaccine-related serotype 6A incidence were inconsistent. Increasing trends of non-vaccine

  10. Preclinical evaluation of a Haemophilus influenzae type b conjugate vaccine process intended for technology transfer.

    Science.gov (United States)

    Hamidi, Ahd; Verdijk, Pauline; Kreeftenberg, Hans

    2014-01-01

    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

  11. Factors that influence parental vaccination decisions for adolescents, 13 to 17 years old: National Immunization Survey-Teen, 2010.

    Science.gov (United States)

    Dorell, Christina; Yankey, David; Kennedy, Allison; Stokley, Shannon

    2013-02-01

    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.

  12. Pediatric invasive pneumococcal disease caused by vaccine serotypes following the introduction of conjugate vaccination in Denmark

    DEFF Research Database (Denmark)

    Harboe, Zitta B; Valentiner-Branth, Palle; Ingels, Helene

    2013-01-01

    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...

  13. Meningococcal vaccines and herd immunity: lessons learned from serogroup C conjugate vaccination programs.

    Science.gov (United States)

    Trotter, Caroline L; Maiden, Martin C J

    2009-07-01

    Effective vaccines provide direct protection to immunized individuals, but may also provide benefits to unvaccinated individuals by reducing transmission and thereby lowering the risk of infection. Such herd immunity effects have been demonstrated following the introduction of meningococcal serogroup C conjugate (MCC) vaccines, with reductions in disease attack rates in unimmunized individuals and significantly lower serogroup C carriage attributable to the vaccine introduction. In the UK, targeting teenagers for immunization was crucial in maximizing indirect effects, as most meningococcal transmission occurs in this age group. Questions remain regarding the duration of herd protection and the most appropriate long-term immunization strategies. The magnitude of the herd effects following MCC vaccination was largely unanticipated, and has important consequences for the design and evaluation of new meningococcal vaccines.

  14. Meningococcal vaccines and herd immunity: lessons learned from serogroup C conjugate vaccination programmes

    Science.gov (United States)

    Trotter, Caroline L; Maiden, Martin C J

    2014-01-01

    Summary Effective vaccines provide direct protection to immunised individuals, but may also provide benefits to unvaccinated individuals by reducing transmission and hence lowering the risk of infection. Such herd immunity effects have been demonstrated following the introduction of meningococcal serogroup C conjugate (MCC) vaccines, with reductions in disease attack rates in unimmunised individuals and significantly lower serogroup C carriage attributable to the vaccine introduction. In the UK targeting teenagers for immunisation was crucial in maximising indirect effects, as most meningococcal transmission occurs in this age group. Questions remain regarding the duration of herd protection and the most appropriate long-term immunisation strategies. The magnitude of the herd effects following MCC vaccination was largely unanticipated, and has important consequences for the design and evaluation of new meningococcal vaccines. PMID:19538112

  15. Costs of vaccine delivery in the Gambia before and after, pentavalent and pneumococcal conjugate vaccine introductions.

    Science.gov (United States)

    Usuf, E; Mackenzie, G; Lowe-Jallow, Y; Boye, B; Atherly, D; Suraratdecha, C; Griffiths, U K

    2014-04-07

    The Gambia introduced seven-valent pneumococcal conjugate vaccine (PCV) in August 2009 and switched to 13-valent PCV in April 2011. In April 2009 monovalent hepatitis B and combined Diphtheria-Tetanus-Pertussis and Haemophilus influenzae type b vaccines were transitioned to a combined pentavalent vaccine. The current schedule offers three doses of PCV and pentavalent, and continues to give children monovalent hepatitis B vaccine at birth. We estimated the overall costs of the Gambian immunisation programme and the incremental costs of introducing pentavalent and the seven-valent PCV. Twenty health facilities out of a total of 56 were surveyed. Data collected included number of vaccine doses delivered, staff time spent on vaccine delivery, distance travelled to collect vaccines, and cold chain expansion due to new vaccine introduction. National level data were collected from key informant interviews. Annualised costs were calculated in 2009 US$. With a PCV price of US$7 per dose, the incremental costs of introducing PCV was US$1.6 million, equivalent to US$25 per fully immunised child, with systems costs accounting for US$1.90. The switch to pentavalent vaccine resulted in cost savings of US$0.45 per fully immunised child. Total annual costs increased by 45% after the introduction of the new vaccines, amounting to US$ 3.0 million, or US$45 per fully immunised child. Vaccine prices were the most important determinant of total incremental costs and cold chain expansion the biggest cost component of systems costs. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. A decade of herd protection after introduction of meningococcal serogroup C conjugate vaccination

    NARCIS (Netherlands)

    Bijlsma, Merijn W.; Brouwer, Matthijs C.; Spanjaard, Lodewijk; van de Beek, Diederik; van der Ende, Arie

    2014-01-01

    Vaccination with meningococcal serogroup C (MenC) conjugate (MCC) polysaccharide vaccines led to a substantial decline in MenC disease in the vaccinated and the unvaccinated population. The decline in the unvaccinated population can be explained by herd protection by reduced colonization of

  17. Effects of Pneumococcal Conjugate Vaccine 2 Years after Its Introduction, the Netherlands

    NARCIS (Netherlands)

    Rodenburg, Gerwin D.; de Greeff, Sabine C.; Jansen, Angelique G. C. S.; de Melker, Hester E.; Schouls, Leo M.; Hak, Eelko; Spanjaard, Lodewijk; Sanders, Elisabeth A. M.; van der Ende, Arie

    In the Netherlands, the 7-valent pneumococcal conjugate vaccine (PCV-7) was implemented in a 3+1-dose schedule in the national immunization program for infants born after April 1, 2006. To assess the vaccine's effectiveness, we compared disease incidence before and after vaccine implementation (June

  18. Effects of pneumococcal conjugate vaccine 2 years after its introduction, the Netherlands

    NARCIS (Netherlands)

    Rodenburg, Gerwin D.; de Greeff, Sabine C.; Jansen, Angelique G. C. S.; de Melker, Hester E.; Schouls, Leo M.; Hak, Eelko; Spanjaard, Lodewijk; Sanders, Elisabeth A. M.; van der Ende, Arie

    2010-01-01

    In the Netherlands, the 7-valent pneumococcal conjugate vaccine (PCV-7) was implemented in a 3+1-dose schedule in the national immunization program for infants born after April 1, 2006. To assess the vaccine's effectiveness, we compared disease incidence before and after vaccine implementation (June

  19. Conjugate and polysaccharide pneumococcal vaccines do not improve initial response of the polysaccharide vaccine in HIV-infected adults.

    Science.gov (United States)

    Peñaranda, Maria; Payeras, Antoni; Cambra, Ana; Mila, Joan; Riera, Melcior

    2010-05-15

    This is a randomized trial to compare the immunoglobulin G response and the antibody avidity after two pneumococcal vaccinations, conjugated pneumococcal vaccine (CPV) and polysaccharide pneumococcal vaccine (PPV) 4 weeks after vs. PPV alone in 202 HIV-infected adults. There were no differences in the two strategies, either in the percentage of immunoglobulin G two-fold increase for the CPV included serotypes or immunoglobulin G two-fold increase, reaching the level of 1 microg/ml except for serotype 23F (26% responded after conjugated pneumococcal vaccine + PPV vs. 14% after PPV). No avidity increases were seen in any strategy.

  20. Decrease in pneumococcal co-colonization following vaccination with the seven-valent pneumococcal conjugate vaccine.

    Directory of Open Access Journals (Sweden)

    Carina Valente

    Full Text Available Understanding the epidemiology of pneumococcal co-colonization is important for monitoring vaccine effectiveness and the occurrence of horizontal gene transfer between pneumococcal strains. In this study we aimed to evaluate the impact of the seven-valent pneumococcal conjugate vaccine (PCV7 on pneumococcal co-colonization among Portuguese children. Nasopharyngeal samples from children up to 6 years old yielding a pneumococcal culture were clustered into three groups: pre-vaccine era (n = 173, unvaccinated children of the vaccine era (n = 169, and fully vaccinated children (4 doses; n = 150. Co-colonization, serotype identification, and relative serotype abundance were detected by analysis of DNA of the total bacterial growth of the primary culture plate using the plyNCR-RFLP method and a molecular serotyping microarray-based strategy. The plyNCR-RFLP method detected an overall co-colonization rate of 20.1%. Microarray analysis confirmed the plyNCR-RFLP results. Vaccination status was the only factor found to be significantly associated with co-colonization: co-colonization rates were significantly lower (p = 0.004; Fisher's exact test among fully vaccinated children (8.0% than among children from the pre-PCV7 era (17.3% or unvaccinated children of the PCV7 era (18.3%. In the PCV7 era there were significantly less non-vaccine type (NVT co-colonization events than would be expected based on the NVT distribution observed in the pre-PCV7 era (p = 0.024. In conclusion, vaccination with PCV7 resulted in a lower co-colonization rate due to an asymmetric distribution between NVTs found in single and co-colonized samples. We propose that some NVTs prevalent in the PCV7 era are more competitive than others, hampering their co-existence in the same niche. This result may have important implications since a decrease in co-colonization events is expected to translate in decreased opportunities for horizontal gene transfer, hindering

  1. National, Regional, State, and Selected Local Area Vaccination Coverage Among Adolescents Aged 13-17 Years - United States, 2016.

    Science.gov (United States)

    Walker, Tanja Y; Elam-Evans, Laurie D; Singleton, James A; Yankey, David; Markowitz, Lauri E; Fredua, Benjamin; Williams, Charnetta L; Meyer, Sarah A; Stokley, Shannon

    2017-08-25

    The Advisory Committee on Immunization Practices (ACIP) recommends that adolescents routinely receive tetanus, diphtheria, and acellular pertussis vaccine (Tdap), meningococcal conjugate vaccine (MenACWY), and human papillomavirus (HPV) vaccine (1) at age 11-12 years. ACIP also recommends catch-up vaccination with hepatitis B vaccine, measles, mumps, and rubella (MMR) vaccine, and varicella vaccine for adolescents who are not up to date with childhood vaccinations. ACIP recommends a booster dose of MenACWY at age 16 years (1). In December 2016, ACIP updated HPV vaccine recommendations to include a 2-dose schedule for immunocompetent adolescents initiating the vaccination series before their 15th birthday (2). To estimate adolescent vaccination coverage in the United States, CDC analyzed data from the 2016 National Immunization Survey-Teen (NIS-Teen) for 20,475 adolescents aged 13-17 years.* During 2015-2016, coverage increased for ≥1 dose of Tdap (from 86.4% to 88.0%) and for each HPV vaccine dose (from 56.1% to 60.4% for ≥1 dose). Among adolescents aged 17 years, coverage with ≥2 doses of MenACWY increased from 33.3% to 39.1%. In 2016, 43.4% of adolescents (49.5% of females; 37.5% of males) were up to date with the HPV vaccination series, applying the updated HPV vaccine recommendations retrospectively. † Coverage with ≥1 HPV vaccine dose varied by metropolitan statistical area (MSA) status and was lowest (50.4%) among adolescents living in non-MSA areas and highest (65.9%) among those living in MSA central cities. § Adolescent vaccination coverage continues to improve overall; however, substantial opportunities exist to further increase HPV-associated cancer prevention.

  2. Pneumococcal conjugate vaccine administration during therapy for pediatric leukemia.

    Science.gov (United States)

    Crawford, Nigel W; Balloch, Anne; Tikkanen, Leena; Merchinaud, Francoise; Downie, Peter; Buttery, Jim P

    2015-01-01

    Pediatric leukemia patients are at high risk of invasive pneumococcal disease. The study aim was to determine the antibody response to a 10-valent pneumococcal conjugate vaccine (PCV10) administered during chemotherapy. An open-label study in pediatric leukemia patients: Group 1 had completed a primary 7-valent (PCV7) course and received a single PCV10 dose. Group 2 were PCV immunization naïve and received 3 doses of PCV10, administered 2 months apart. Serum samples were taken at baseline and 1 month post each PCV10 dose. Antipneumococcal serotype-specific IgG to 10 serotypes were measured by enzyme-linked immunosorbent assay and the functional response to 4 serotypes (1, 6B, 19F and 23F) was measured using opsonophagocytic assays. Thirty-nine participants were recruited between May 2010 and January 2011; group 1 (n = 27) and group 2 (n = 12). The diagnosis was acute lymphoblastic leukemia (38) and acute myeloid leukemia (1). Median age was 6.2 years (1.7-17.2 years) with 62% male. The median time from diagnosis to baseline serology was 7.4 months (1.6-36.8 months). At baseline, protective geometric mean concentration above the threshold (>0.35 μg/mL) ranged from 5.3% (serotype 4) to 71% (serotype 19F). More than 60% of participants in both groups were above threshold postimmunization for 7 of the 10 PCV serotypes. Opsonophagocytic assay correlated with enzyme-linked immunosorbent assay for 3 of the 4 serotypes and r ranged from 0.51 to 0.84. An injection-site reaction was reported in 73% (27/37). It is safe to administer PCV10 vaccine during therapy for pediatric leukemia. It provided a satisfactory serum immune response for the majority of vaccine serotypes.

  3. Otitis media in children vaccinated during consecutive 7-valent or 10-valent pneumococcal conjugate vaccination schedules

    Science.gov (United States)

    2014-01-01

    Background 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). Methods 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. Results 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. Conclusions 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

  4. Otitis media in children vaccinated during consecutive 7-valent or 10-valent pneumococcal conjugate vaccination schedules.

    Science.gov (United States)

    Leach, Amanda Jane; Wigger, Christine; Andrews, Ross; Chatfield, Mark; Smith-Vaughan, Heidi; Morris, Peter Stanley

    2014-08-11

    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

  5. Pediatric invasive pneumococcal disease caused by vaccine serotypes following the introduction of conjugate vaccination in Denmark.

    Directory of Open Access Journals (Sweden)

    Zitta B Harboe

    Full Text Available 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 PCV7 in the program, mainly due to a decline in IPD caused by PCV7-serotypes. We report the results from a nationwide population-based cohort study of laboratory confirmed IPD cases in children younger than 5 years during October 1, 2007 to December 31, 2010 and describe the characteristics 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 and 23F. One case of vaccine failure was observed in a severely immunosuppressed child following three PCV7 doses, and two cases were observed in immunocompetent children following two infant doses before they were eligible for their booster. None of the IPD cases caused by the additional PCV13 serotypes had been vaccinated by PCV13 and there were therefore no PCV13-vaccine failures in the first 8-months after PCV13 introduction in Denmark.

  6. Beyond new vaccine introduction: the uptake of pneumococcal conjugate vaccine in the African Region.

    Science.gov (United States)

    Olayinka, Folake; Ewald, Leah; Steinglass, Robert

    2017-01-01

    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.

  7. Cost-effectiveness and Health Benefits of Pediatric 23-valent Pneumococcal Polysaccharide Vaccine, 7-valent Pneumococcal Conjugate Vaccine and Forecasting 13-valent Pneumococcal Conjugate Vaccine in China.

    Science.gov (United States)

    Mo, Xiuting; Gai Tobe, Ruoyan; Liu, Xiaoyan; Mori, Rintaro

    2016-11-01

    Each year in China, approximately 700,000 children under 5 years old are diagnosed with pneumonia, and 30,000 die of the disease. Although 7-valent pneumococcal conjugate vaccine (PCV-7) and 23-valent pneumococcal polysaccharide vaccine (PPV-23) are available in China, the costs are borne by the consumer, resulting in low coverage for PCV-7. We aimed to conduct a simulation study to assess the cost-effectiveness and health benefits of PCV-7, 13-valent pneumococcal conjugate vaccine (PCV-13) and PPV-23 to prevent childhood pneumonia and other vaccine-preventive diseases in China. An economic evaluation was performed using a Markov simulation model. Parameters including demographic, epidemiological data, costs and efficacy of vaccines were obtained from previous studies. A hypothetical cohort of 100,000 newborns (focusing on pneumococcal diseases ≤7 years old) was followed up until death or 100 years of age. The model incorporated the impact of vaccination on reduction of incidence of pneumococcal diseases and mortality of children ≤7 years. Outcomes are presented in terms of disease cases averted, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio. Under baseline assumptions, PPV-23 is currently the only cost-effective option, whereas PCV-13 showed the greatest impact on pneumococcal disease burden, reducing invasive pneumococcal diseases by 31.3%, pneumonia by 15.3% and gaining 73.8 QALYs (10,000 individuals at discount rate of 3%). Incremental cost-effectiveness ratios of PCV-13 and PCV-7 are US$29,460/QALY and US$104,094/QALY, respectively, showing no cost-effectiveness based on the World Health Organization recommended willingness-to-pay threshold. On the other hand, the incremental cost-effectiveness ratios of PCVs were most sensitive to vaccination costs; if it reduces 4.7% and 32.2% for PCV-7 and PCV-13, respectively, the vaccination will be cost-effective. To scale up current vaccination strategies and achieve potential health

  8. Stunting correlates with high salivary and serum antibody levels after 13-valent pneumococcal conjugate vaccination of Venezuelan Amerindian children

    NARCIS (Netherlands)

    Verhagen, Lilly M; Hermsen, Meyke; Rivera-Olivero, Ismar; Sisco, María Carolina; Pinelli, Elena; Hermans, Peter W M; Berbers, Guy A M; de Waard, Jacobus H; de Jonge, Marien I

    2016-01-01

    OBJECTIVE: To determine the impact of pre-vaccination nutritional status on vaccine responses in Venezuelan Warao Amerindian children vaccinated with the 13-valent pneumococcal conjugate vaccine (PCV13) and to investigate whether saliva can be used as read-out for these vaccine responses. METHODS: A

  9. Reduced-dose schedules with pneumococcal conjugate vaccine: impact on nasopharyngeal carriage and herd immunity

    NARCIS (Netherlands)

    van Gils, E.J.M.

    2011-01-01

    The success of the 4-dose schedule with 7-valent pneumococcal conjugate vaccine (PCV7) is based on direct protection against vaccine serotype pneumococcal disease in vaccinees but also on the observed large herd effect in unvaccinated age groups. However, the nasopharyngeal vacant niche is filled by

  10. Identifying optimal vaccination strategies for serogroup A Neisseria meningitidis conjugate vaccine in the African meningitis belt.

    Directory of Open Access Journals (Sweden)

    Sara Tartof

    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

  11. Carrier priming or suppression: understanding carrier priming enhancement of anti-polysaccharide antibody response to conjugate vaccines.

    Science.gov (United States)

    Pobre, Karl; Tashani, Mohamed; Ridda, Iman; Rashid, Harunor; Wong, Melanie; Booy, Robert

    2014-03-14

    With the availability of newer conjugate vaccines, immunization schedules have become increasingly complex due to the potential for unpredictable immunologic interference such as 'carrier priming' and 'carrier induced epitopic suppression'. Carrier priming refers to an augmented antibody response to a carbohydrate portion of a glycoconjugate vaccine in an individual previously primed with the carrier protein. This review aims to provide a critical evaluation of the available data on carrier priming (and suppression) and conceptualize ways by which this phenomenon can be utilized to strengthen vaccination schedules. We conducted this literature review by searching well-known databases to date to identify relevant studies, then extracted and synthesized the data on carrier priming of widely used conjugate polysaccharide vaccines, such as, pneumococcal conjugate vaccine (PCV), meningococcal conjugate vaccine (MenCV) and Haemophilus influenzae type b conjugate vaccines (HibV). We found evidence of carrier priming with some conjugate vaccines, particularly HibV and PCV, in both animal and human models but controversy surrounds MenCV. This has implications for the immunogenicity of conjugate polysaccharide vaccines following the administration of tetanus-toxoid or diphtheria-toxoid containing vaccine (such as DTP). Available evidence supports a promising role for carrier priming in terms of maximizing the immunogenicity of conjugate vaccines and enhancing immunization schedule by making it more efficient and cost effective. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Protein conjugate polysaccharide vaccines: Challenges in development and global implementation

    Directory of Open Access Journals (Sweden)

    Manisha Nair

    2012-01-01

    Replacement by nonvaccine serotypes;capsule switching;time duration of the antibody protective effect following vaccination;costs of the vaccines, programme costs, lack of knowledge of the disease burden, and targeting population groups for vaccination.

  13. Update on the use of meningococcal serogroup C CRM₁₉₇-conjugate vaccine (Meningitec) against meningitis.

    Science.gov (United States)

    Badahdah, Al-Mamoon; Rashid, Harunor; Khatami, Ameneh

    2016-01-01

    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.

  14. Surveillance of the impact of pneumococcal conjugate vaccines in developing countries.

    Science.gov (United States)

    Rodgers, Gail L; Klugman, Keith P

    2016-01-01

    Infection due to Streptococcus pneumoniae is a leading cause of morbidity and mortality in young children, especially in developing countries. With the support of Gavi, the Vaccine Alliance, the majority of these countries have introduced pneumococcal conjugate vaccines (PCV) into their national immunization programs and early data demonstrate a high degree of effectiveness, translating to enormous public health benefit through both direct and indirect (herd) effects. Future vaccination strategy may be focused on maintaining herd effects rather than individual protection. Evaluation of vaccine-type carriage, particularly in pneumonia cases, may be an easy, feasible way of measuring continued vaccine impact.

  15. Kinetics of antibody responses after primary immunization with meningococcal serogroup C conjugate vaccine or secondary immunization with either conjugate or polysaccharide vaccine in adults

    NARCIS (Netherlands)

    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.

    2009-01-01

    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

  16. Immunogenicity of a combination vaccine containing pneumococcal conjugates and meningococcal PorA OMVs.

    Science.gov (United States)

    van den Dobbelsteen, Germie P J M; van Dijken, Harry H; Pillai, Subramonia; van Alphen, Loek

    2007-03-22

    The pre-clinical immunogenicity of a combination vaccine containing 13-valent pneumococcal conjugate (13vPnC) vaccine (serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F conjugated to CRM197) and nine-valent meningococcal B PorA vaccine (NonaMen; serosubtypes P1.7,16; P1.5-1,2-2; P1.19,15-1; P1.5-2,10; P1.12-1,13; P1.7-2,4; P1.22,14; P1.7-1,1 and P1.18-1,3,6), and any potential immunological interference between pneumococcal and MenB components of the vaccine were evaluated. NIH mice were immunized twice subcutaneously with the vaccines combined in one syringe, or given individually. Combining 13vPnC vaccine with NonaMen vaccine in one syringe had no negative effect on the induced antibody response against any MenB serosubtypes compared to separate injection of the vaccines, and the anti-pneumococcal antibody responses were enhanced. Furthermore, co-administration of the combination vaccine with a combined diphtheria/tetanus/acellular pertussis/inactivated poliomyelitis vaccine/Haemophilus influenzae type b-TT conjugate (DTaP/IPV-Hib) vaccine to New Zealand white rabbits at a different injection site did not affect the anti-pneumococcal polysaccharide and anti-PorA antibody titres. We conclude that no immunological interference was observed by combined administration of pneumococcal conjugate and meningococcal B vaccines in one syringe.

  17. 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.

    Science.gov (United States)

    Tashani, M; Alfelali, M; Barasheed, O; Alqahtani, A S; Heron, L; Wong, M; Rashid, H; Booy, R

    2016-11-21

    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

  18. Biosynthesis of Conjugate Vaccines Using an O-Linked Glycosylation System

    Directory of Open Access Journals (Sweden)

    Chao Pan

    2016-04-01

    Full Text Available Conjugate vaccines are known to be one of the most effective and safest types of vaccines against bacterial pathogens. Previously, vaccine biosynthesis has been performed by using N-linked glycosylation systems. However, the structural specificity of these systems for sugar substrates has hindered their application. Here, we report a novel protein glycosylation system (O-linked glycosylation via Neisseria meningitidis that can transfer virtually any glycan to produce a conjugate vaccine. We successfully established this system in Shigella spp., avoiding the construction of an expression vector for polysaccharide synthesis. We further found that different protein substrates can be glycosylated using this system and that the O-linked glycosylation system can also effectively function in other Gram-negative bacteria, including some strains whose polysaccharide structure was not suitable for conjugation using the N-linked glycosylation system. The results from a series of animal experiments show that the conjugate vaccine produced by this O-linked glycosylation system offered a potentially protective antibody response. Furthermore, we elucidated and optimized the recognition motif, named MOOR, for the O-glycosyltransferase PglL. Finally, we demonstrated that the fusion of other peptides recognized by major histocompatibility complex class II around MOOR had no adverse effects on substrate glycosylation, suggesting that this optimized system will be useful for future vaccine development. Our results expand the glycoengineering toolbox and provide a simpler and more robust strategy for producing bioconjugate vaccines against a variety of pathogens.

  19. Serotype-Specific Changes in Invasive Pneumococcal Disease after Pneumococcal Conjugate Vaccine Introduction: A Pooled Analysis of Multiple Surveillance Sites

    NARCIS (Netherlands)

    Feikin, Daniel R.; Kagucia, Eunice W.; Loo, Jennifer D.; Link-Gelles, Ruth; Puhan, Milo A.; Cherian, Thomas; Levine, Orin S.; Whitney, Cynthia G.; O'Brien, Katherine L.; Moore, Matthew R.; Adegbola, Claire A.; Agocs, Mary; Ampofo, Krow; Andrews, Nick; Barton, Theresa; Benito, Javier; Broome, Claire V.; Bruce, Michael G.; Bulkow, Lisa R.; Byington, Carrie L.; Camou, Teresa; Cook, Heather; Cotter, Suzanne; Dagan, Ron; de Wals, Philippe; Deceuninck, Geneviève; Denham, Barbara; Edwards, Giles; Eskola, Juhani; Fitzgerald, Margaret; Galanakis, Emmanouil; Garcia-Gabarrot, Gabriela; Garcia-Garcia, Juan J.; Gene, Amadeu; Gomez, Borja; Heffernan, Helen; Hennessy, Thomas W.; Heuberger, Sigrid; Hilty, Markus; Ingels, Helene; Jayasinghe, Sanjay; Kellner, James D.; Klein, Nicola P.; Kormann-Klement, Andrea; Kozakova, Jana; Krause, Vicki; Kriz, Paula; Lambertsen, Lotte; Lepoutre, Agnès; Lipsitch, Marc; Lopez-Vega, Mariana; Lovgren, Marguerite; Maraki, Sofia; Mason, Edward O.; McIntyre, Peter B.; Menzies, Robert; Messina, Allison; Miller, Elizabeth; Mintegi, Santiago; Motlova, Jitka; Moulton, Lawrence H.; Mühlemann, Kathrin; Muñoz-Almagro, Carmen; Murdoch, David R.; Park, Daniel E.; Reingold, Arthur L.; Sa-Leao, Raquel; Sanyal, Abanti; Smith, Peter G.; Spanjaard, Lodewijk; Techasaensiri, Chonnamet; Thompson, Richard E.; Thoon, Koh C.; Tyrrell, Gregory J.; Valentiner-Branth, Palle; van der Ende, Arie; Vanderkooi, Otto G.; van der Linden, Mark P. G.; Varon, Emmanuelle; Verhaegen, Jan; Vestrheim, Didrik F.; Vickers, Imelda; von Gottberg, Anne; von Kries, Rüdiger; Waight, Pauline; Weatherholtz, Robert; Weiss, Susanne; Yee, Arnold; Zaidi, Anita K. M.

    2013-01-01

    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-vaccineserotype (NVT) IPD rates occurred in some sites, presumably

  20. Invasive pneumococcal disease in patients with haematological malignancies before routine use of conjugate vaccines in Finland.

    Science.gov (United States)

    Lindström, Vesa; Aittoniemi, Janne; Lyytikäinen, Outi; Klemets, Peter; Ollgren, Jukka; Silvennoinen, Raija; Nuorti, J Pekka; Sinisalo, Marjatta

    2016-01-01

    The baseline national invasive pneumococcal disease (IPD) incidence rate, serotype distribution and serotype coverage of pneumococcal vaccines were evaluated in patients with Hodgkin's and non-Hodgkin's lymphomas, myeloma and leukaemia within 1 year after haematological diagnosis during 1995-2002, before introduction of pneumococcal conjugate vaccines. Pneumococcal serotype distribution among these patients was different from serotypes causing IPD in the general population. The serotype coverages of PCV13 and PPSV23 were 57% and 64%, respectively, lower than in the general population. This reflects a higher predisposition to IPD in vaccinated patients with haematological malignancies and possibly less benefit of herd immunity gained with the wide use of pneumococcal conjugate vaccines in the general population. This data will be useful as a baseline for determining the future role of adult PCV vaccination in these patient groups.

  1. Effectiveness of Haemophilus influenzae type b conjugate vaccine introduction into routine childhood immunization in Kenya

    Science.gov (United States)

    Cowgill, Karen D.; Ndiritu, Moses; Nyiro, Joyce; Slack, Mary P. E.; Chiphatsi, Salome; Ismail, Amina; Kamau, Tatu; Mwangi, Isaiah; English, Mike; Newton, Charles R. J. C.; Feikin, Daniel R.; Scott, J. Anthony G.

    2006-01-01

    Context Haemophilus influenzae type b (Hib) conjugate vaccine is not perceived as a public health priority in Africa because data on Hib disease burden and vaccine effectiveness are scarce. Hib immunization was introduced in Kenyan infants in 2001. Objective to define invasive Hib disease incidence and Hib vaccine program effectiveness. Design, Setting, Patients culture-based surveillance for invasive Hib disease at Kilifi District Hospital from 2000 to 2005 was linked to demographic surveillance of 38,000 children aged <5 years in Kilifi District, Kenya. HIV infection and Hib vaccination status were determined for children with Hib disease admitted 2002–2005. Interventions Conjugate Hib vaccine within the routine childhood immunization program at ages 6, 10 and 14 weeks from November 2001 Main outcome measures Incidence of culture-proven Hib invasive disease before and after vaccine introduction and vaccine program effectiveness (1-incidence rate ratio) Results Prior to vaccine introduction the median age of Hib cases was 8 months; case fatality was 23%. Among children aged <5 years the annual incidence of invasive Hib disease 1 year before and 1 and 3 years after vaccine introduction was 66, 47 and 7.6 per 100,000, respectively. For children <2 years, incidence was 119, 82 and 16, respectively. In 2004–2005 vaccine effectiveness was 88% (95% CI 73–96%) among children <5 years and 87% (95% CI 66–96%) among children <2 years. Of 53 Hib cases admitted during 2002–2005, 29 (55%) were age-ineligible to have received vaccine, 12 (23%) had not been vaccinated despite being eligible, and 12 (23%) had received ≥2 doses of vaccine (2 were HIV-positive). Conclusions In Kenya, introduction of Hib vaccine into the routine childhood immunization program reduced Hib disease incidence among children aged <5 years to 12% of its baseline level. This impact was not observed until the third year after vaccine introduction. PMID:16896110

  2. Predicting the impact of new pneumococcal conjugate vaccines: serotype composition is not enough.

    Science.gov (United States)

    Hausdorff, William P; Hoet, Bernard; Adegbola, Richard A

    2015-03-01

    Streptococcus pneumoniae is a major cause of childhood morbidity and mortality worldwide. A heptavalent polysaccharide-protein conjugate vaccine (PCV) has proven highly effective in preventing pneumococcal disease in industrialized countries. Two higher-valent pneumococcal conjugate vaccines are now widely available, even in the poorest countries. These differ from each other in the number of serotypes and carrier proteins used for their conjugation. Some have assumed that the only meaningful clinical difference between PCV formulations is a function of the number of serotypes each contains. A careful review of recent clinical data with these and several unlicensed PCV formulations points to important similarities but also that some key properties of each vaccine likely differ from one another.

  3. New pneumococcal conjugate vaccine introductions in four sub ...

    African Journals Online (AJOL)

    Although health sector workers perceived increases in the coverage of other vaccines following the introduction of PCV, ... type. Date of vaccine introduction. Data collection period. Introduction strategy. Catch up strategy. Other relevant features. Cameroon. PCV13 July 2011. May – June ..... change in vaccination coverage.

  4. Non-epitope-specific suppression of the antibody response to Haemophilus influenzae type b conjugate vaccines by preimmunization with vaccine components

    DEFF Research Database (Denmark)

    Barington, T; Skettrup, M; Juul, L

    1993-01-01

    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...

  5. Impact of infant pneumococcal conjugate vaccination on community acquired pneumonia hospitalization in all ages in the Netherlands

    NARCIS (Netherlands)

    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.

    2017-01-01

    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

  6. Impact of infant pneumococcal conjugate vaccination on community acquired pneumonia hospitalization in all ages in the Netherlands.

    NARCIS (Netherlands)

    van Deursen, A M M; Schurink-Van't Klooster, T M; Man, W H; van de Kassteele, J; van Gageldonk-Lafeber, A B; Bruijning-Verhagen, P C J L; de Melker, H E; Sanders, E A M; Knol, M J

    2017-01-01

    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 impact of PCVs

  7. Antibody Persistence in Young Children 5 Years after Vaccination with a Combined Haemophilus influenzae Type b-Neisseria meningitidis Serogroup C Conjugate Vaccine Coadministered with Diphtheria-Tetanus-Acellular Pertussis-Based and Pneumococcal Conjugate Vaccines.

    Science.gov (United States)

    Tejedor, Juan Carlos; Brzostek, Jerzy; Konior, Ryszard; Grunert, Detlef; Kolhe, Devayani; Baine, Yaela; Van Der Wielen, Marie

    2016-07-01

    We evaluated antibody persistence in children up to 5 years after administration of a combined Haemophilus influenzae type b (Hib)-Neisseria meningitidis serogroup C (MenC)-tetanus toxoid (TT) conjugate vaccine coadministered with a pneumococcal conjugate vaccine. This is the follow-up study of a randomized trial (ClinicalTrials.gov registration no. NCT00334334/00463437) in which healthy children were vaccinated (primary vaccinations at 2, 4, and 6 months of age and booster vaccination at 11 to 18 months of age) with Hib-MenC-TT or a control MenC conjugate vaccine, coadministered with diphtheria-tetanus-acellular pertussis (DTPa)-based combination vaccines (DTPa/Hib for control groups) and a pneumococcal conjugate vaccine (10-valent pneumococcal nontypeable H. influenzae protein D conjugate vaccine [PHiD-CV] or 7-valent cross-reacting material 197 [CRM197] conjugate vaccine [7vCRM]). MenC antibody titers were measured with a serum bactericidal antibody (SBA) assay using rabbit complement (i.e., rabbit SBA [rSBA]), and antibodies against Hib polyribosylribitol phosphate (PRP) were measured with an enzyme-linked immunosorbent assay. Antibody persistence up to 5 years after booster vaccination is reported for 530 children ∼6 years of age. The percentages of children with seroprotective rSBA-MenC titers were between 24.2% and 40.1% in all groups approximately 5 years after booster vaccination. More than 98.5% of children in each group retained seroprotective anti-PRP concentrations. No vaccine-related serious adverse events and no events related to a lack of vaccine efficacy were reported. Approximately 5 years after booster vaccination, the majority of children retained seroprotective anti-PRP antibody concentrations. The percentage of children retaining seroprotective rSBA-MenC titers was low (≤40%), suggesting that a significant proportion of children may be unprotected against MenC disease. (This study has been registered at ClinicalTrials.gov under

  8. A clinical trial examining the effect of increased total CRM(197) carrier protein dose on the antibody response to Haemophilus influenzae type b CRM(197) conjugate vaccine.

    Science.gov (United States)

    Usonis, Vytautas; Bakasenas, Vytautas; Lockhart, Stephen; Baker, Sherryl; Gruber, William; Laudat, France

    2008-08-18

    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.

  9. Optimization of the conjugation method for a serogroup B/C meningococcal vaccine.

    Science.gov (United States)

    Fukasawa, Lucila O; Schenkman, Rocilda P F; Perciani, Catia T; Carneiro, Sylvia M; Dias, Waldely O; Tanizaki, Martha M

    2006-11-01

    A conjugate meningococcal vaccine against serogroup B/C consisting of capsular PS (polysaccharide) from serogroup C conjugated to OMV (outer membrane vesicle) from serogroup B would be a very useful vaccine in regions where there is a prevalence of both serogroups, for example in Brazil. For this purpose, the conjugation method that uses ADHy (adipic acid dihydrazide) as spacer and a carbodi-imide derivative, EDAC [1-ethyl-3-(3-dimethylaminopropyl)carbodi-imide], as catalyser was optimized looking for synthesis yield and maintenance of the antigenicity of both components. The best synthesis conditions preserving the vaccine immunogenicity resulted in a final yield of approx. 17%. Immunogenicity of the vaccine was highest when 10% of the sialic acid residues of the PS were occupied by the ADHy spacer. Sterilization of the conjugate by filtration through a 0.22-microm-pore-size membrane resulted in a low recovery of protein and PS (approximately 50%), although the vaccine immunogenicity was maintained. Using gamma irradiation on freeze-dried sample, it was possible to maintain the integrity of OMV structure and, consequently, its ability to induce bactericidal antibodies.

  10. Cost-effectiveness of pneumococcal conjugate vaccination in Latin America and the Caribbean: a regional analysis.

    Science.gov (United States)

    Sinha, Anushua; Constenla, Dagna; Valencia, Juan Esteban; O'Loughlin, Rosalyn; Gomez, Elizabeth; de la Hoz, Fernando; Valenzuela, Maria Teresa; de Quadros, Ciro A

    2008-11-01

    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. 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. 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. 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.

  11. Developmental strategy fora new Group A meningococcal conjugate vaccine (MenAfriVacR).

    Science.gov (United States)

    Kulkarni, Prasad S; Jadhav, Suresh S; LaForce, F Marc

    2017-10-19

    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.

  12. Cost-Effectiveness of Vaccinating Immunocompetent ≥65 Year Olds with the 13-Valent Pneumococcal Conjugate Vaccine in England.

    Science.gov (United States)

    van Hoek, Albert Jan; Miller, Elizabeth

    2016-01-01

    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

  13. [Study on immunogenicity of group A and group C meningococcal conjugate vaccine with coupling group B meningococcal outer membrane protein].

    Science.gov (United States)

    Ma, Fu-Bao; Tao, Hong; Wang, Hong-Jun

    2009-10-01

    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.

  14. Structural correlates of carrier protein recognition in tetanus toxoid-conjugated bacterial polysaccharide vaccines.

    Science.gov (United States)

    Lockyer, Kay; Gao, Fang; Derrick, Jeremy P; Bolgiano, Barbara

    2015-03-10

    An analysis of structure-antibody recognition relationships in nine licenced polysaccharide-tetanus toxoid (TT) conjugate vaccines was performed. The panel of conjugates used included vaccine components to protect against disease caused by Haemophilus influenzae type b, Neisseria meningitidis groups A, C, W and Y and Streptococcus pneumoniae serotype 18C. Conformation and structural analysis included size exclusion chromatography with multi-angle light scattering to determine size, and intrinsic fluorescence spectroscopy and fluorescence quenching to evaluate the protein folding and exposure of Trp residues. A capture ELISA measured the recognition of TT epitopes in the conjugates, using four rat monoclonal antibodies: 2 localised to the HC domain, and 2 of which were holotoxoid conformation-dependent. The conjugates had a wide range of average molecular masses ranging from 1.8×10(6) g/mol to larger than 20×10(6) g/mol. The panel of conjugates were found to be well folded, and did not have spectral features typical of aggregated TT. A partial correlation was found between molecular mass and epitope recognition. Recognition of the epitopes either on the HC domain or the whole toxoid was not necessarily hampered by the size of the molecule. Correlation was also found between the accessibility of Trp side chains and polysaccharide loading, suggesting also that a higher level of conjugated PS does not necessarily interfere with toxoid accessibility. There were different levels of carrier protein Trp side-chain and epitope accessibility that were localised to the HC domain; these were related to the saccharide type, despite the conjugates being independently manufactured. These findings extend our understanding of the molecular basis for carrier protein recognition in TT conjugate vaccines. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

  15. Economic impact of pneumococcal conjugate vaccination in Brazil, Chile, and Uruguay.

    Science.gov (United States)

    Constenla, Dagna O

    2008-08-01

    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.

  16. 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⋆.

    Science.gov (United States)

    Tashani, Mohamed; Heron, Leon; Wong, Melanie; Rashid, Harunor; Booy, Robert

    2017-07-01

    : 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

  17. Estimating the Clinical and Economic Impact of Maintaining use of 13-valent Pneumococcal Conjugate Vaccine (PCV13) in Mexico

    OpenAIRE

    Wasserman, Matt; Wilson, Michele; McDade, Cheryl; Grajales, Ana Gabriela; Palacios, Maria Gabriela; Baez- Revueltas, Fabiola Berenice; Farkouh, Raymond

    2017-01-01

    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...

  18. Pneumococcal conjugate vaccine – a health priority | Zar | South ...

    African Journals Online (AJOL)

    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 ...

  19. Persistence of Serogroup C Antibody Responses Following Quadrivalent Meningococcal Conjugate Vaccination in United States Military Personnel

    Science.gov (United States)

    2014-05-14

    available at ScienceDirect Vaccine j our na l ho me page: www.elsev ier .com/ locate /vacc ine ersistence of serogroup C antibody responses following...22] Auckland C, Gray S, Borrow R, Andrews N, Goldblatt D, Ramsay M, et al. Clinical and immunologic risk factors for meningococcal C conjugate

  20. Experimental vaccination of pigs with an Actinobacillus pleuropneumoniae serotype 5b capsular polysaccharide tetanus toxoid conjugate

    DEFF Research Database (Denmark)

    Andresen, Lars Ole; Jacobsen, M.J.; Nielsen, J.P.

    1997-01-01

    The protective efficacy of an Actinobacillus pleuropneumoniae serotype 5b capsular polysaccharide-tetanus toroid conjugate (Ap5bCP-TT) against homologous challenge of pigs was investigated. Four pigs were non-vaccinated controls (group A), 4 pigs were injected with adjuvant without antigen (group B...

  1. Comparing Haemophilus influenzae type b conjugate vaccine schedules: a systematic review and meta-analysis of vaccine trials.

    Science.gov (United States)

    Low, Nicola; Redmond, Shelagh M; Rutjes, Anne W S; Martínez-González, Nahara A; Egger, Matthias; di Nisio, Marcello; Scott, Pippa

    2013-11-01

    The optimal schedule and the need for a booster dose are unclear for Haemophilus influenzae type b (Hib) conjugate vaccines. We systematically reviewed relative effects of Hib vaccine schedules. We searched 21 databases to May 2010 or June 2012 and selected randomized controlled trials or quasi-randomized controlled trials that compared different Hib schedules (3 primary doses with no booster dose [3p+0], 3p+1 and 2p+1) or different intervals in primary schedules and between primary and booster schedules. Outcomes were clinical efficacy, nasopharyngeal carriage and immunological response. Results were combined in random-effects meta-analysis. Twenty trials from 15 countries were included; 16 used vaccines conjugated to tetanus toxoid (polyribosylribitol phosphate conjugated to tetanus toxoid). No trials assessed clinical or carriage outcomes. Twenty trials examined immunological outcomes and found few relevant differences. Comparing polyribosylribitol phosphate conjugated to tetanus toxoid 3p+0 with 2p+0, there was no difference in seropositivity at the 1.0 μg/mL threshold by 6 months after the last primary dose (combined risk difference -0.02; 95% confidence interval: -0.10, 0.06). Only small differences were seen between schedules starting at different ages, with different intervals between primary doses, or with different intervals between primary and booster doses. Individuals receiving a booster were more likely to be seropositive than those at the same age who did not. There is no clear evidence from trials that any 2p+1, 3p+0 or 3p+1 schedule of Hib conjugate vaccine is likely to provide better protection against Hib disease than other schedules. Until more data become available, scheduling is likely to be determined by epidemiological and programmatic considerations in individual settings.

  2. Effect of nationwide vaccination of 3-month-old infants in The Netherlands with conjugate Haemophilus influenzae type b vaccine: high efficacy and lack of herd immunity

    NARCIS (Netherlands)

    van Alphen, L.; Spanjaard, L.; van der Ende, A.; Schuurman, I.; Dankert, J.

    1997-01-01

    OBJECTIVE: The effect of nationwide vaccination in The Netherlands with conjugate Haemophilus influenzae type b vaccine on the incidence of H. influenzae meningitis was assessed in the first 3 years after the introduction of vaccination to the birth cohort at 3 months of age. STUDY DESIGN: Children

  3. Huge impact of assumptions on indirect effects on the cost-effectiveness of routine infant vaccination with 7-valent conjugate vaccine (Prevnar (R))

    NARCIS (Netherlands)

    Rozenbaum, Mark H.; van Hoek, Albert Jan; Hak, Eelko; Postma, Maarten J.

    2010-01-01

    Several recently published European cost-effectiveness studies on the 7-valent pneumococcal conjugate vaccine (PCV-7: Prevnar (R)) have included net-indirect vaccine benefits for non-vaccine protected groups into their studies, which might be too optimistic an approach given recent data.

  4. Quantitation of antibody-secreting cells in the blood after vaccination with Haemophilus influenzae type b conjugate vaccine

    DEFF Research Database (Denmark)

    Barington, T; Heilmann, C; Andersen, V

    1990-01-01

    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...... capsular polysaccharides from Hib and pneumococci. The predominance of IgA AbSC in response to both conjugate and pure polysaccharide vaccines is probably due to reactivation of the same clones of IgA-committed memory B cells originally primed at the mucosa by natural exposure to the polysaccharide...

  5. Immunosuppressive drugs impairs antibody response of the polysaccharide and conjugated pneumococcal vaccines in patients with Crohn's disease

    DEFF Research Database (Denmark)

    Kantsø, Bjørn; Halkjær, Sofie Ingdam; Thomsen, Ole Østergaard

    2015-01-01

    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...

  6. The impact of protein-conjugate polysaccharide vaccines: an endgame for meningitis?

    Science.gov (United States)

    Maiden, Martin C J

    2013-08-05

    The development and implementation of conjugate polysaccharide vaccines against invasive bacterial diseases, specifically those caused by the encapsulated bacteria Neisseria meningitidis, Haemophilus influenzae and Streptococcus pneumoniae, has been one of the most effective public health innovations of the last 25 years. These vaccines have resulted in significant reductions in childhood morbidity and mortality worldwide, with their effectiveness due in large part to their ability to induce long-lasting immunity in a range of age groups. At the population level this immunity reduces carriage and interrupts transmission resulting in herd immunity; however, these beneficial effects can be counterbalanced by the selection pressures that immunity against carriage can impose, potentially promoting the emergence and spread of virulent vaccine escape variants. Studies following the implementation of meningococcal serogroup C vaccines improved our understanding of these effects in relation to the biology of accidental pathogens such as the meningococcus. This understanding has enabled the refinement of the implementation of conjugate polysaccharide vaccines against meningitis-associated bacteria, and will be crucial in maintaining and improving vaccine control of these infections. To date there is little evidence for the spread of virulent vaccine escape variants of the meningococcus and H. influenzae, although this has been reported in pneumococci.

  7. Pneumococcal conjugate vaccine failure in children: A systematic review of the literature.

    Science.gov (United States)

    Oligbu, Godwin; Hsia, Yingfen; Folgori, Laura; Collins, Sarah; Ladhani, Shamez

    2016-12-07

    Pneumococcal conjugate vaccines (PCVs) are highly effective in preventing pneumococcal invasive disease (IPD) due to serotypes included in the vaccines. The risk of vaccine-type IPD in immunised children (i.e. vaccine failure) has not been systematically assessed in countries with established PCV programmes. We undertook a systematic review of the English literature published from January 2000 to April 2016 to evaluate the vaccine schedule, risk factors, serotype distribution, clinical presentation and outcomes of vaccine failure in children vaccinated with the 7-valent (PCV7), 10-valent (PCV10), and 13-valent (PCV13) vaccines. Data sources included MEDLINE, EMBASE, Cochrane library, and references within identified articles. We identified 1742 potential studies and included 20 publications involving 7584 participants in children aged ⩽5year-olds: 5202 received 2 doses followed by a booster in 10 studies, (68.6%), 64 (0.8%) received 3 doses without a booster in 2 studies, and 2318 received a 3+1 schedule (30.6%) in 8 studies. A total of 159 vaccine failure cases were identified, representing 2.1% [95% CI: 1.8-2.4%] of the reported IPD cases. Most studies did not report clinical characteristics or outcomes. Among eight studies reporting comorbidities, 33/77 patients (42.9%) had an underlying condition. The main serotypes associated with vaccine failure were 19F (51/128 cases with known serotype; 39.8%), 6B (33/128; 25.8%), and 4 (10/128; 7.8%). Only five studies reported patient outcomes, with a crude case fatality rate of 2.4% (2/85; 95%CI: 0.3-8.5%). Pneumococcal conjugate vaccines have been implemented in national immunisation programmes for more than a decade, yet there are only a few studies reporting vaccine failure. PCV failure is rare, irrespective of vaccine or schedule. Co-morbidity prevalence was high amongst vaccine failure cases but case fatality rate was relatively low. There is a need for more systematic reporting vaccine failure cases in countries

  8. Cost-effectiveness analysis of a universal vaccination programme with the 7-valent pneumococcal conjugate vaccine (PCV-7) in Sweden

    DEFF Research Database (Denmark)

    Bergman, Annika; Hjelmgren, Jonas; Ortqvist, Ake

    2008-01-01

    that vaccination of 1 cohort could potentially prevent 9 cases of pneumococcal meningitis, 22 cases of pneumococcal septicaemia, 509 cases of hospitalized pneumonia, 7812 cases of acute otitis media, and 2.7 fatalities, among children 0-4 y of age and 6 episodes of pneumococcal meningitis and 167 cases......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...

  9. Is a single dose of meningococcal serogroup C conjugate vaccine sufficient for protection? experience from the Netherlands

    Directory of Open Access Journals (Sweden)

    Kaaijk Patricia

    2012-02-01

    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.

  10. Nasopharyngeal Bacterial Carriage in the Conjugate Vaccine Era with a Focus on Pneumococci

    Directory of Open Access Journals (Sweden)

    V. T. Devine

    2015-01-01

    Full Text Available Seven-valent pneumococcal conjugate vaccine (PCV7 was included in the UK national immunisation program in 2006, and this was replaced by thirteen-valent PCV in 2010. During this time, the carriage of vaccine-type Streptococcus pneumoniae decreased but pneumococcal carriage remained stable due to increases in non-vaccine-type S. pneumoniae. Carriage studies have been undertaken in various countries to monitor vaccine-type replacement and to help predict the serotypes, which may cause invasive disease. There has been less focus on how conjugate vaccines indirectly affect colonization of other nasopharyngeal bacteria. If the nasopharynx is treated as a niche, then bacterial dynamics are accepted to occur. Alterations in these dynamics have been shown due to seasonal changes, antibiotic use, and sibling/day care interaction. It has been shown that, following PCV7 introduction, an eradication of pneumococcal vaccine types has resulted in increases in the abundance of other respiratory pathogens including Haemophilus influenzae and Staphylococcus aureus. These changes are difficult to attribute to PCV7 introduction alone and these studies do not account for further changes due to PCV13 implementation. This review aims to describe nasopharyngeal cocarriage of respiratory pathogens in the PCV era.

  11. Enhanced control of Mycobacterium tuberculosis extrapulmonary dissemination in mice by an arabinomannan-protein conjugate vaccine.

    Directory of Open Access Journals (Sweden)

    Rafael Prados-Rosales

    2017-03-01

    Full Text Available Currently there are a dozen or so of new vaccine candidates in clinical trials for prevention of tuberculosis (TB and each formulation attempts to elicit protection by enhancement of cell-mediated immunity (CMI. In contrast, most approved vaccines against other bacterial pathogens are believed to mediate protection by eliciting antibody responses. However, it has been difficult to apply this formula to TB because of the difficulty in reliably eliciting protective antibodies. Here, we developed capsular polysaccharide conjugates by linking mycobacterial capsular arabinomannan (AM to either Mtb Ag85b or B. anthracis protective antigen (PA. Further, we studied their immunogenicity by ELISA and AM glycan microarrays and protection efficacy in mice. Immunization with either Abg85b-AM or PA-AM conjugates elicited an AM-specific antibody response in mice. AM binding antibodies stimulated transcriptional changes in Mtb. Sera from AM conjugate immunized mice reacted against a broad spectrum of AM structural variants and specifically recognized arabinan fragments. Conjugate vaccine immunized mice infected with Mtb had lower bacterial numbers in lungs and spleen, and lived longer than control mice. These findings provide additional evidence that humoral immunity can contribute to protection against Mtb.

  12. Cost-effectiveness of conjugate pneumococcal vaccination in Singapore: comparing estimates for 7-valent, 10-valent, and 13-valent vaccines.

    Science.gov (United States)

    Tyo, Karen Richards; Rosen, Melissa M; Zeng, Wu; Yap, Mabel; Pwee, Keng Ho; Ang, Li Wei; Shepard, Donald S

    2011-09-02

    Although multiple studies of cost-effectiveness of pneumococcal conjugate vaccines have been conducted, no such study has examined Singapore's situation nor compared the licensed conjugate vaccines in an Asian population. This paper estimates the costs and public health impacts of pneumococcal conjugate vaccine programs, varying estimates of serotype replacement and herd immunity effects as key parameters in the analysis. Based in part on a 2008 analysis also presented here, Singapore has approved the PCV-7, PHiD-10, and PCV-13 pneumococcal conjugate vaccines as part of its National Childhood Immunisation Programme. An economic evaluation was performed using a Markov simulation model populated with Singapore-specific population parameters, vaccine costs, treatment costs, and disease incidence data. The vaccinated infant and child cohort of 226,000 was 6% of the Singapore resident population of 3.8 million. Vaccine efficacy estimates were constructed for PCV-7, PHiD-10, and PCV-13 vaccines based on their serotype coverage in Singapore and compared to 'no vaccination'. The model estimated impacts over a five-year time horizon with 3% per year discounting of costs and health effects. Costs were presented in 2010 U.S. dollars (USD) and Singapore dollars (SGD). Sensitivity analyses included varying herd immunity, serotype replacement rates, vaccine cost, and efficacy against acute otitis media. Under base case assumptions for the revised analysis (i.e., herd effects in the unvaccinated population equivalent to 20% of direct effects) PCV-13 prevented 834 cases and 7 deaths due to pneumonia, meningitis, and bacteremia in the vaccinated population, and 952 cases and 191 deaths in the unvaccinated population over the 5-year time horizon. Including herd effects, the cost-effectiveness ratio for PCV-13 was USD $37,644 (SGD $51,854) per QALY. Without herd effects, however, the ratio was USD $204,535 (SGD $281,743) per QALY. The PCV-7 cost per QALY including herd effects was

  13. Do pneumococcal conjugate vaccines provide any cross-protection against serotype 19A?

    Directory of Open Access Journals (Sweden)

    Hoet Bernard

    2010-02-01

    Full Text Available Abstract Background Introduction of the 7-valent pneumococcal conjugate vaccine (7vCRM in several countries has led to a rapid, significant drop in vaccine-type invasive pneumococcal disease (IPD in immunized children. In the United States and some other countries with high antibiotic use, a subsequent rise in serotype 19A IPD has been taken to indicate that the 19F conjugate in the vaccine provides no cross-protection against the immunologically related 19A. Discussion We systematically assessed the clinical efficacy and effectiveness of 19F-containing vaccines against 19A disease or nasopharyngeal carriage by searching English-language articles in the electronic databases PubMed, Current contents, Scopus, and Embase from 1985 to 2008. The vaccine efficacy and effectiveness point estimates were consistently positive for modest protection against 19A IPD and acute otitis media (AOM. However, statistical significance was not reached in any individual study. No consistent impact of 7vCRM on 19A nasopharyngeal colonization could be detected. These findings are discussed in context of immunogenicity analyses indicating that 7vCRM induces functionally active anti-19A antibodies after the booster dose, and that other 19F-containing vaccine formulations may elicit higher levels of such antibodies after both primary and booster doses. Summary Taken together, these results suggest that 19F-conjugates can provide some protection against 19A disease. The magnitude of this protection in a given setting will likely depend on several factors. These include the anti-19A immunogenicity of the specific vaccine formulation, the number of doses of that formulation needed to elicit the response, and the burden of 19A disease that occurs after those doses. It is possible that a modest protective effect may be obscured by the presence of countervailing selection pressures (such as high antibiotic use that favor an increase in colonization with antibiotic

  14. 13-valent pneumococcal conjugate vaccine given with meningococcal C-tetanus toxoid conjugate and other routine pediatric vaccinations: immunogenicity and safety.

    Science.gov (United States)

    Martinón-Torres, Federico; Gimenez-Sanchez, Francisco; Gurtman, Alejandra; Bernaola, Enrique; Diez-Domingo, Javier; Carmona, Alfonso; Sidhu, Mohinder; Sarkozy, Denise A; Gruber, William C; Emini, Emilio A; Scott, Daniel A

    2012-04-01

    As multiple vaccines are administered concomitantly during routine pediatric immunizations, it is important to ascertain the potential interference of any new vaccine on the immune response to the concomitantly administered vaccines. Immune responses to meningococcal serogroup C-tetanus toxoid conjugate vaccine (MnCC-TT) and the diphtheria and tetanus antigens in routine pediatric vaccines (diphtheria, tetanus, acellular pertussis-hepatitis B virus-inactivated poliovirus/Haemophilus influenza type b [DTaP-HBV-IPV/Hib] and DTaP-IPV+Hib) when given concomitantly with the 13-valent pneumococcal conjugate vaccine (PCV13) were compared with responses when given with PCV7. In addition, the immunogenicity and safety of PCV13 were assessed. Healthy infants were randomized to receive PCV13 or PCV7 (ages 2, 4, 6 and 15 months), concomitant with MnCC-TT (2, 4 and 15 months), DTaP-HBV-IPV/Hib (2, 4 and 6 months), and DTaP-IPV+Hib (15 months). Immune responses to MnCC-TT and to the diphtheria and tetanus antigens administered with PCV13 were noninferior to the responses observed when the vaccines were administered with PCV7; ≥96.6 (postinfant) and ≥99.4% (posttoddler) subjects achieved prespecified immune response levels to each antigen in each group. After the infant series, ≥93.0% of subjects receiving PCV13 achieved pneumococcal anticapsular immunoglobulin G concentrations ≥0.35 µg/mL for all serotypes except serotype 3 (86.2%), increasing to 98.1-100% for most serotypes (serotype 3: 93.6%) after the toddler dose. Local and systemic reactions were similar between groups. Immune responses to MnCC-TT, and other childhood vaccines (DTaP-HBV-IPV/Hib, DTaP-IPV+Hib) were noninferior when concomitantly administered with PCV13 compared with PCV7. PCV13 does not interfere with MnCC-TT. PCV13 is highly immunogenic with a favorable safety profile.

  15. Cost effectiveness of pneumococcal vaccination among Dutch infants: economic analysis of the seven valent pneumococcal conjugated vaccine and forecast for the 10 valent and 13 valent vaccines

    NARCIS (Netherlands)

    Rozenbaum, Mark H.; Sanders, Elisabeth A. M.; van Hoek, Albert Jan; Jansen, Angelique G. S. C.; van der Ende, Arie; van den Dobbelsteen, Germie; Rodenburg, Gerwin D.; Hak, Eelko; Postma, Maarten J.

    2010-01-01

    OBJECTIVES: To update cost effectiveness estimates for the four dose (3+1) schedule of the seven valent pneumococcal conjugated vaccine (PCV-7) in the Netherlands and to explore the impact on cost effectiveness of reduced dose schedules and implementation of 10 valent and 13 valent pneumococcal

  16. Outer membrane protein complex of Meningococcus enhances the antipolysaccharide antibody response to pneumococcal polysaccharide-CRM₁₉₇ conjugate vaccine.

    Science.gov (United States)

    Lai, Zengzu; Schreiber, John R

    2011-05-01

    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.

  17. Pneumococcal Conjugate Vaccines and Otitis Media: An Appraisal of the Clinical Trials

    Science.gov (United States)

    Fletcher, Mark A.; Fritzell, Bernard

    2012-01-01

    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

  18. Opsonic and protective properties of antibodies raised to conjugate vaccines targeting six Staphylococcus aureus antigens.

    Directory of Open Access Journals (Sweden)

    Clarissa Pozzi

    Full Text Available Staphylococcus aureus is a major cause of nosocomial and community-acquired infections for which a vaccine is greatly desired. Antigens found on the S. aureus outer surface include the capsular polysaccharides (CP of serotype 5 (CP5 or 8 (CP8 and/or a second antigen, a β-(1→6-polymer of N-acetyl-D-glucosamine (PNAG. Antibodies specific for either CP or PNAG antigens have excellent in vitro opsonic killing activity (OPKA, but when mixed together have potent interference in OPKA and murine protection. To ascertain if this interference could be abrogated by using a synthetic non-acetylated oligosaccharide fragment of PNAG, 9GlcNH(2, in place of chemically partially deacetylated PNAG, three conjugate vaccines consisting of 9GlcNH(2 conjugated to a non-toxic mutant of alpha-hemolysin (Hla H35L, CP5 conjugated to clumping factor B (ClfB, or CP8 conjugated to iron-surface determinant B (IsdB were used separately to immunize rabbits. Opsonic antibodies mediating killing of multiple S. aureus strains were elicited for all three vaccines and showed carbohydrate antigen-specific reductions in the tissue bacterial burdens in animal models of S. aureus skin abscesses, pneumonia, and nasal colonization. Carrier-protein specific immunity was also shown to be effective in reducing bacterial levels in infected lungs and in nasal colonization. However, use of synthetic 9GlcNH(2 to induce antibody to PNAG did not overcome the interference in OPKA engendered when these were combined with antibody to either CP5 or CP8. Whereas each individual vaccine showed efficacy, combining antisera to CP antigens and PNAG still abrogated individual OPKA activities, indicating difficulty in achieving a multi-valent vaccine targeting both the CP and PNAG antigens.

  19. Impact of meningococcal serogroup C conjugate vaccines on carriage and herd immunity.

    Science.gov (United States)

    Maiden, Martin C J; Ibarz-Pavón, Ana Belén; Urwin, Rachel; Gray, Stephen J; Andrews, Nicholas J; Clarke, Stuart C; Walker, A Mark; Evans, Meirion R; Kroll, J Simon; Neal, Keith R; Ala'aldeen, Dlawer A A; Crook, Derrick W; Cann, Kathryn; Harrison, Sarah; Cunningham, Richard; Baxter, David; Kaczmarski, Edward; Maclennan, Jenny; Cameron, J Claire; Stuart, James M

    2008-03-01

    In 1999, meningococcal serogroup C conjugate (MCC) vaccines were introduced in the United Kingdom for those under 19 years of age. The impact of this intervention on asymptomatic carriage of meningococci was investigated to establish whether serogroup replacement or protection by herd immunity occurred. Multicenter surveys of carriage were conducted during vaccine introduction and on 2 successive years, resulting in a total of 48,309 samples, from which 8599 meningococci were isolated and characterized by genotyping and phenotyping. A reduction in serogroup C carriage (rate ratio, 0.19) was observed that lasted at least 2 years with no evidence of serogroup replacement. Vaccine efficacy against carriage was 75%, and vaccination had a disproportionate impact on the carriage of sequence type (ST)-11 complex serogroup C meningococci that (rate ratio, 0.06); these meningococci also exhibited high rates of capsule expression. The impact of vaccination with MCC vaccine on the prevalence of carriage of group C meningococci was consistent with herd immunity. The high impact on the carriage of ST-11 complex serogroup C could be attributed to high levels of capsule expression. High vaccine efficacy against disease in young children, who were not protected long-term by the schedule initially used, is attributed to the high vaccine efficacy against carriage in older age groups.

  20. Cost effectiveness analysis of heptavalent pneumococcal conjugate vaccine in Germany considering herd immunity effects.

    Science.gov (United States)

    Claes, Christa; Reinert, Ralf René; von der Schulenburg, Johann-Matthias Graf

    2009-02-01

    In Germany the heptavalent pneumococcal conjugate vaccine (PCV7) has been recommended as a general infant vaccination since 2006. Data from similar programmes in the USA have reported a reduction of pneumococcal diseases in both vaccinated and unvaccinated populations, suggesting herd immunity effects. This study analyses the cost-effectiveness of a general vaccination with PCV7 in Germany based on these findings. A Markov model adapts efficacy and herd immunity data to the German population. Further main model inputs are incidence, vaccination uptake, serotype distribution, case fatality rates, and vaccination and health-care costs. A general vaccination with PCV7 would avoid about 232,000 pneumococcal infections and 1,879 premature deaths per year in Germany. From the health-care payer's perspective, direct cost savings would outweigh vaccination expenditures by a ratio of 1:1.16. The sensitivity analysis shows that these estimates are quite conservative. Based on the health-economic evaluation, the authors recommend the continuation of the general recommendation of PCV7 according to the 3 + 1 schedule within the German Statutory Health Insurance.

  1. Effectiveness of different vaccine schedules for heptavalent and 13-valent conjugate vaccines against pneumococcal disease in the Community of Madrid.

    Science.gov (United States)

    Latasa, P; Ordobás, M; Garrido-Estepa, M; Gil de Miguel, A; Sanz, J C; Barranco, M D; Insúa, E; García-Comas, L

    2017-09-25

    The heptavalent pneumococcal conjugate vaccine (PCV-7) was added to the childhood routine vaccination program in the Community of Madrid in November of 2006 with 3+1 recommended doses and a catch-up for those under 2years old. In June 2010, PCV-7 was replaced by 13-valent vaccine (PCV-13) with 2+1 recommended doses. In July of 2012, the PCV-13 was removed from the funded program and reintroduced again (2+1 recommended doses) in December 2014. In between, children were vaccinated privately with 3+1 recommended doses of PCV-13. The aim of this study was to evaluate the effectiveness of each vaccination schedule used in the Community of Madrid. We included all cases of invasive pneumococcal disease (IPD) reported between 2007 and 2015 to the Notifiable Diseases Surveillance System. Vaccination information was obtained from the Immunization Registry. Vaccine effectiveness (VE) was estimated using the indirect cohort design for cases with serotype information. A total 779 cases were included in the study. Among them 47.6% of the cases were primo-vaccinated with booster, 20% primo-vaccinated, 15.9% incompletely primo-vaccinated and 16.5% not vaccinated. The VE for ≥1 doses of any PCV was 82% (CI 95%: 67.8-89.9%): 91.9% (CI 95%: 76.5-97.2%) for PCV-7 and 77.2% (48.6-89.9%) for PCV-13. VE in those receiving the full 2+1 or 3+1 schedules was 100% for both vaccines. A high number of vaccine failures were reported in children before they had the opportunity to receive the booster dose, especially due to PCV-13-non-PCV-7 serotypes. VE was higher for PCV-7 compared to PCV-13, except for those that received the complete schedule with booster that achieved 100% of VE, which shows the relevance of the vaccines and complying with all doses scheduled. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. The cost-effectiveness of a 13-valent pneumococcal conjugate vaccination for infants in England.

    Science.gov (United States)

    van Hoek, Albert Jan; Choi, Yoon Hong; Trotter, Caroline; Miller, Elizabeth; Jit, Mark

    2012-11-26

    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.

  3. Pneumococcal meningitis: epidemiological profile pre- and post-introduction of the pneumococcal 10-valent conjugate vaccine.

    Science.gov (United States)

    Hirose, Tatiane E; Maluf, Eliane M C P; Rodrigues, Cristina O

    2015-01-01

    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. 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). 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%). 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. Copyright © 2014 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  4. High-dimensional assessment of B-cell responses to quadrivalent meningococcal conjugate and plain polysaccharide vaccine.

    Science.gov (United States)

    O'Connor, Daniel; Clutterbuck, Elizabeth A; Thompson, Amber J; Snape, Matthew D; Ramasamy, Maheshi N; Kelly, Dominic F; Pollard, Andrew J

    2017-01-30

    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.

  5. Economics of an adolescent meningococcal conjugate vaccination catch-up campaign in the United States.

    Science.gov (United States)

    Ortega-Sanchez, Ismael R; Meltzer, Martin I; Shepard, Colin; Zell, Elizabeth; Messonnier, Mark L; Bilukha, Oleg; Zhang, Xinzhi; Stephens, David S; Messonnier, Nancy E

    2008-01-01

    In June 2005, the Advisory Committee on Immunization Practices recommended the newly licensed quadrivalent meningococcal conjugate vaccine for routine use among all US children aged 11 years. A 1-time catch-up vaccination campaign for children and adolescents aged 11-17 years, followed by routine annual immunization of each child aged 11 years, could generate immediate herd immunity benefits. The objective of our study was to analyze the cost-effectiveness of a catch-up vaccination campaign with quadrivalent meningococcal conjugate vaccine for children and adolescents aged 11-17 years. We built a probabilistic model of disease burden and economic impacts for a 10-year period with and without a program of adolescent catch-up meningococcal vaccination, followed by 9 years of routine immunization of children aged 11 years. We used US age- and serogroup-specific surveillance data on incidence and mortality. Assumptions related to the impact of herd immunity were drawn from experience with routine meningococcal vaccination in the United Kingdom. We estimated costs per case, deaths prevented, life-years saved, and quality-adjusted life-years saved. With herd immunity, the catch-up and routine vaccination program for adolescents would prevent 8251 cases of meningococcal disease in a 10-year period (a 48% decrease). Excluding program costs, this catch-up and routine vaccination program would save US$551 million in direct costs and $920 million in indirect costs, including costs associated with permanent disability and premature death. At $83 per vaccinee, the catch-up vaccination would cost society approximately $223,000 per case averted, approximately $2.6 million per death prevented, approximately $127,000 per life-year saved, and approximately $88,000 per quality-adjusted life-year saved. Targeting counties with a high incidence of disease decreased the cost per life-year saved by two-thirds. Although costly, catch-up and routine vaccination of adolescents can have a

  6. Purification and characterization of a Shigella conjugate vaccine, produced by glycoengineering Escherichia coli.

    Science.gov (United States)

    Ravenscroft, Neil; Haeuptle, Micha A; Kowarik, Michael; Fernandez, Fabiana S; Carranza, Paula; Brunner, Andreas; Steffen, Michael; Wetter, Michael; Keller, Sacha; Ruch, Corina; Wacker, Michael

    2016-01-01

    Shigellosis remains a major cause of diarrheal disease in developing countries and causes substantial morbidity and mortality in children. Glycoconjugate vaccines consisting of bacterial surface polysaccharides conjugated to carrier proteins are the most effective vaccines for controlling invasive bacterial infections. Nevertheless, the development of a multivalent conjugate vaccine to prevent Shigellosis has been hampered by the complex manufacturing process as the surface polysaccharide for each strain requires extraction, hydrolysis, chemical activation and conjugation to a carrier protein. The use of an innovative biosynthetic Escherichia coli glycosylation system substantially simplifies the production of glycoconjugates. Herein, the Shigella dysenteriae type 1 (Sd1) O-polysaccharide is expressed and its functional assembly on an E. coli glycosyl carrier lipid is demonstrated by HPLC analysis and mass spectrometry. The polysaccharide is enzymatically conjugated to specific asparagine residues of the carrier protein by co-expression of the PglB oligosaccharyltransferase and the carrier protein exotoxin A (EPA) from Pseudomonas aeruginosa. The extraction and purification of the Shigella glycoconjugate (Sd1-EPA) and its detailed characterization by the use of physicochemical methods including NMR and mass spectrometry is described. The report shows for the first time that bioconjugation provides a newly developed and improved approach to produce an Sd1 glycoconjugate that can be characterized using state-of-the-art techniques. In addition, this generic process together with the analytical methods is ideally suited for the production of additional Shigella serotypes, allowing the development of a multivalent Shigella vaccine. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  7. [Vaccinal strategies in response to new epidemiological challenges in 2010. Reasonable hope for a "B" meningococcal vaccine].

    Science.gov (United States)

    Nicolas, P

    2010-08-01

    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.

  8. Effect of 7-valent pneumococcal conjugate vaccine on nasopharyngeal carriage with Haemophilus influenzae and Moraxella catarrhalis in a randomized controlled trial

    NARCIS (Netherlands)

    van Gils, Elske J M; Veenhoven, Reinier H; Rodenburg, Gerwin D; Hak, Eelko; Sanders, Elisabeth A M

    2011-01-01

    Seven-valent CRM197-conjugated pneumococcal conjugate vaccine (PCV7(CRM197)) reduces both vaccine serotype nasopharyngeal colonization and vaccine serotype acute otitis media by 50-60%. However, overall pneumococcal carriage and impact on otitis media are partly offset by concomitant increase of

  9. [Meningococcal C conjugate vaccine: Impact of a vaccination program and long-term effectiveness in Navarra, Spain, 2000-2014].

    Science.gov (United States)

    Morales, Desirée; García-Cenoz, Manuel; Moreno, Laura; Bernaola, Enrique; Barricarte, Aurelio; Castilla, Jesús

    2016-12-01

    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 © 2015 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  10. Design and production of conjugate vaccines againstS.Paratyphi Ausing an O-linked glycosylation system in vivo.

    Science.gov (United States)

    Sun, Peng; Pan, Chao; Zeng, Ming; Liu, Bo; Liang, Haoyu; Wang, Dongshu; Liu, Xiankai; Wang, Bin; Lyu, Yufei; Wu, Jun; Zhu, Li; Wang, Hengliang

    2018-01-01

    Enteric fever, mainly caused by Salmonella enterica serovar Paratyphi A , remains a common and serious infectious disease worldwide. As yet, there are no licensed vaccines against S . Paratyphi A . Biosynthesis of conjugate vaccines has become a promising approach against bacterial infection. However, the popular biosynthetic strategy using N-linked glycosylation systems does not recognize the specialized O-polysaccharide structure of S . Paratyphi A . Here, we describe an O-linked glycosylation approach, the only currently available glycosylation system suitable for an S . Paratyphi A conjugate vaccine. We successfully generated a recombinant S . Paratyphi A strain with a longer O-polysaccharide chain and transformed the O-linked glycosylation system into the strain. Thus, we avoided the need for construction of an O-polysaccharide expression vector. In vivo assays indicated that this conjugate vaccine could evoke IgG1 antibody to O-antigen of S . Paratyphi A strain CMCC 50973 and elicit bactericidal activity against S . Paratyphi A strain CMCC 50973 and five other epidemic strains. Furthermore, we replaced the peptides after the glycosylation site (Ser) with an antigenic peptide (P2). The results showed that the anti-lipopolysaccharide antibody titer, bactericidal activity of serum, and protective effect during animal challenge could be improved, indicating a potential strategy for further vaccine design. Our system provides an easier and more economical method for the production of S . Paratyphi A conjugate vaccines. Modification of the glycosylation site sequon provides a potential approach for the development of next-generation "precise conjugate vaccines."

  11. Effectively introducing a new meningococcal A conjugate vaccine in Africa: the Burkina Faso experience.

    Science.gov (United States)

    Djingarey, Mamoudou H; Barry, Rodrigue; Bonkoungou, Mete; Tiendrebeogo, Sylvestre; Sebgo, Rene; Kandolo, Denis; Lingani, Clement; Preziosi, Marie-Pierre; Zuber, Patrick L F; Perea, William; Hugonnet, Stéphane; Dellepiane de Rey Tolve, Nora; Tevi-Benissan, Carole; Clark, Thomas A; Mayer, Leonard W; Novak, Ryan; Messonier, Nancy E; Berlier, Monique; Toboe, Desire; Nshimirimana, Deo; Mihigo, Richard; Aguado, Teresa; Diomandé, Fabien; Kristiansen, Paul A; Caugant, Dominique A; Laforce, F Marc

    2012-05-30

    A new Group A meningococcal (Men A) conjugate vaccine, MenAfriVac™, was prequalified by the World Health Organization (WHO) in June 2010. Because Burkina Faso has repeatedly suffered meningitis epidemics due to Group A Neisseria meningitidis special efforts were made to conduct a country-wide campaign with the new vaccine in late 2010 and before the onset of the next epidemic meningococcal disease season beginning in January 2011. In the ensuing five months (July-November 2010) the following challenges were successfully managed: (1) doing a large safety study and registering the new vaccine in Burkina Faso; (2) developing a comprehensive communication plan; (3) strengthening the surveillance system with particular attention to improving the capacity for real-time polymerase chain reaction (PCR) testing of spinal fluid specimens; (4) improving cold chain capacity and waste disposal; (5) developing and funding a sound campaign strategy; and (6) ensuring effective collaboration across all partners. Each of these issues required specific strategies that were managed through a WHO-led consortium that included all major partners (Ministry of Health/Burkina Faso, Serum Institute of India Ltd., UNICEF, Global Alliance for Vaccines and Immunization, Meningitis Vaccine Project, CDC/Atlanta, and the Norwegian Institute of Public Health/Oslo). Biweekly teleconferences that were led by WHO ensured that problems were identified in a timely fashion. The new meningococcal A conjugate vaccine was introduced on December 6, 2010, in a national ceremony led by His Excellency Blaise Compaore, the President of Burkina Faso. The ensuing 10-day national campaign was hugely successful, and over 11.4 million Burkinabes between the ages of 1 and 29 years (100% of target population) were vaccinated. African national immunization programs are capable of achieving very high coverage for a vaccine desired by the public, introduced in a well-organized campaign, and supported at the highest

  12. 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

    NARCIS (Netherlands)

    Jansen, Angelique G S C; Sanders, Elisabeth A M; Hoes, Arno W; van Loon, Anton M; Hak, Eelko

    2008-01-01

    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

  13. Pneumococcal conjugate vaccination does not induce a persisting mucosal IgA response in children with recurrent acute otitis media.

    NARCIS (Netherlands)

    Bogaert, D.; Veenhoven, R.H.; Ramdin, R.; Luijendijk, I.H.; Rijkers, G.T.; Sanders, E.A.M.; Groot, R. de; Hermans, P.W.M.

    2005-01-01

    AIM: In a prospective controlled study in young children with a history of recurrent acute otitis media, we analyzed the salivary IgA and IgG antibody titers upon vaccination with a 7-valent pneumococcal conjugate vaccine (PCV) given once or twice, followed by a 23-valent polysaccharide booster

  14. Economic evaluation of meningococcal serogroup C conjugate vaccination programmes in the Netherlands and its impact on decision-making

    NARCIS (Netherlands)

    Welte, R; van den Dobbelsteen, G; Bos, JM; de Melker, H; van Alphen, L; Spanjaard, L; Rumke, HC; Postma, MJ

    2004-01-01

    The cost-effectiveness of one time vaccination of all persons aged 14 months to 18 years (catch-up programme) and of routine childhood immunisation at either ages 2 + 3 + 4 months, 5 + 6 months, or 14 months with a meningococcal C conjugate vaccine was estimated for The Netherlands, from a societal

  15. Economic evaluation of meningococcal serogroup C conjugate vaccination programmes in The Netherlands and its impact on decision-making

    NARCIS (Netherlands)

    Welte, R.; van den Dobbelsteen, G.; Bos, J. M.; de Melker, H.; van Alphen, L.; Spanjaard, L.; Rümke, H. C.; Postma, M. J.

    2004-01-01

    The cost-effectiveness of one time vaccination of all persons aged 14 months to 18 years (catch-up programme) and of routine childhood immunisation at either ages 2 + 3 + 4 months, 5 + 6 months, or 14 months with a meningococcal C conjugate vaccine was estimated for The Netherlands, from a societal

  16. Vi-CRM 197 as a new conjugate vaccine against Salmonella Typhi.

    Science.gov (United States)

    Micoli, F; Rondini, S; Pisoni, I; Proietti, D; Berti, F; Costantino, P; Rappuoli, R; Szu, S; Saul, A; Martin, L B

    2011-01-17

    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 © 2010 Elsevier Ltd. All rights reserved.

  17. Impact of Pneumococcal Conjugate Vaccination on Otitis Media: A Systematic Review

    Science.gov (United States)

    Taylor, Sylvia; Marchisio, Paola; Vergison, Anne; Harriague, Julie; Hausdorff, William P.; Haggard, Mark

    2012-01-01

    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

  18. Correlation of group C meningococcal conjugate vaccine response with B- and T-lymphocyte activity.

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    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.

  19. Is there a potential role for protein‐conjugate pneumococcal vaccine in older

    Directory of Open Access Journals (Sweden)

    Daniel M. Musher

    2012-04-01

    Full Text Available Longstanding controversy over the efficacy of 23‐valentpneumococcal polysaccharide vaccine (PPV23 led to arecommendation by the Joint Committee on Vaccinationand Immunisation (JCVI of the United Kingdom in March2011, to discontinue routine use of PPV23 in older adults.1Following careful review of the evidence and feedbackfrom stakeholders, the JCVI decided to retain the originalpolicy of uniform vaccination of adults >65 years of age,while keeping the subject under continued review. In theUnited States, the Advisory Committee on ImmunizationPractices (ACIP which is also concerned about the efficacyof PPV23 is currently considering a different strategy, i.e.adding 13‐valent pneumococcal protein‐conjugate vaccine(PCV13 for recommended use in adults, following recentFood and Drug Administration (FDA approval for thispurpose in adults over 50 years of age. It is thereforetimely to review the options for prevention ofpneumococcal disease in adults.

  20. Incidence and types of adverse events during mass vaccination campaign with the meningococcal a conjugate vaccine (MENAFRIVAC™) in Cameroon.

    Science.gov (United States)

    Ateudjieu, Jerome; Stoll, Beat; Nguefack-Tsague, Georges; Yakum, Martin Ndinakie; Mengouo, Marcellin Nimpa; Genton, Blaise

    2016-10-01

    A new vaccine against meningitis A was introduced in Africa meningitis belt in 2010. This study was planned to describe the incidence and types of adverse events following immunization (AEFIs) with a new conjugate vaccine against meningitis A (MenAfrivac™) in a Cameroonian vaccination campaign. The campaign was conducted in Adamawa and North West regions in December 2012 and the AEFIs enhanced surveillance from December 2012 to January 2013. Incidence rates (IR) of overall and serious AEFIs were estimated as well as AEFI incidence rates by type, age group and region. AEFI symptoms were aggregated in System Organ Class (SOC). Of 2 093 381 persons vaccinated, 1352 AEFIs were reported. Of these, 228 (16.9%) were excluded because of not meeting inclusion criteria and 1124 (83.1%) included (IR: 53.7/100 000 doses administered/8 weeks). Of the 82 serious AEFIs reported, 52 (63.2%) met the case definition. 23 (28.1%) were investigated, of which 4 (17.4%) were probably vaccine product-related reactions (IR: 0.2/100 000 doses administered/8 weeks). Fever was the most common reported AEFI with 626 cases (IR: 31.4/100 000 doses administered/8 weeks). The proportion of people with the SOC "Gastrointestinal disorders" was significantly lower in ages 5-15 and 16-29 years than 1-4 years [aRR = 0.63(0.42-0.93) and 0.54(0.36-0.81) respectively]. Incidence and types of AEFI reported during MenAfriVac TM vaccination campaign organized in Cameroon in 2012 did not suggest concern regarding the vaccine safety. Differences in frequency of AEFIs types per age group could guide the monitoring of AEFIs frequency in future campaigns. Efforts are needed to improve the investigation rate of serious AEFIs. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  1. Development of a Pfs25-EPA malaria transmission blocking vaccine as a chemically conjugated nanoparticle.

    Science.gov (United States)

    Shimp, Richard L; Rowe, Christopher; Reiter, Karine; Chen, Beth; Nguyen, Vu; Aebig, Joan; Rausch, Kelly M; Kumar, Krishan; Wu, Yimin; Jin, Albert J; Jones, David S; Narum, David L

    2013-06-19

    Successful efforts to control infectious diseases have often required the use of effective vaccines. The current global strategy for control of malaria, including elimination and eradication will also benefit from the development of an effective vaccine that interrupts malaria transmission. To this end, a vaccine that disrupts malaria transmission within the mosquito host has been investigated for several decades targeting a 25 kDa ookinete specific surface protein, identified as Pfs25. Phase 1 human trial results using a recombinant Pfs25H/Montanide ISA51 formulation demonstrated that human Pfs25 specific antibodies block parasite infectivity to mosquitoes; however, the extent of blocking was likely insufficient for an effective transmission blocking vaccine. To overcome the poor immunogenicity, processes to produce and characterize recombinant Pfs25H conjugated to a detoxified form of Pseudomonas aeruginosa exoprotein A (EPA) have been developed and used to manufacture a cGMP pilot lot for use in human clinical trials. The Pfs25-EPA conjugate appears as a nanoparticle with an average molar mass in solution of approximately 600 kDa by static light scattering with an average diameter 20 nm (range 10-40 nm) by dynamic light scattering. The molar ratio of Pfs25H to EPA is about 3 to 1 by amino acid analysis, respectively. Outbred mice immunized with the Pfs25-EPA conjugated nanoparticle formulated on Alhydrogel(®) had a 75-110 fold increase in Pfs25H specific antibodies when compared to an unconjugated Pfs25H/Alhydrogel(®) formulation. A phase 1 human trial using the Pfs25-EPA/Alhydrogel(®) formulation is ongoing in the United States. Published by Elsevier Ltd.

  2. From individual to herd protection with pneumococcal vaccines: the contribution of the Cuban pneumococcal conjugate vaccine implementation strategy

    Directory of Open Access Journals (Sweden)

    Nivaldo Linares-Pérez

    2017-07-01

    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.

  3. From individual to herd protection with pneumococcal vaccines: the contribution of the Cuban pneumococcal conjugate vaccine implementation strategy.

    Science.gov (United States)

    Linares-Pérez, Nivaldo; Toledo-Romaní, María E; Santana-Mederos, Darielys; García-Fariñas, Anaí; García-Rivera, Dagmar; Valdés-Balbín, Yury; Vérez-Bencomo, Vicente

    2017-07-01

    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. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  4. Evaluation of 13-valent pneumococcal conjugate vaccine and concomitant meningococcal group C conjugate vaccine in healthy infants and toddlers in Spain.

    Science.gov (United States)

    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

    2013-11-04

    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

  5. Cost-effectiveness of new pneumococcal conjugate vaccines in Turkey: a decision analytical model

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    Bakır Mustafa

    2012-11-01

    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.

  6. S. pneumoniae transmission according to inclusion in conjugate vaccines: Bayesian analysis of a longitudinal follow-up in schools

    Directory of Open Access Journals (Sweden)

    Valleron Alain-Jacques

    2006-01-01

    Full Text Available Abstract Background Recent trends of pneumococcal colonization in the United States, following the introduction of conjugate vaccination, indicate that non-vaccine serotypes tend to replace vaccine serotypes. The eventual extent of this replacement is however unknown and depends on serotype-specific carriage and transmission characteristics. Methods Here, some of these characteristics were estimated for vaccine and non-vaccine serotypes from the follow-up of 4,488 schoolchildren in France in 2000. A Bayesian approach using Markov chain Monte Carlo data augmentation techniques was used for estimation. Results Vaccine and non-vaccine serotypes were found to have similar characteristics: the mean duration of carriage was 23 days (95% credible interval (CI: 21, 25 days for vaccine serotypes and 22 days (95% CI: 20, 24 days for non-vaccine serotypes; within a school of size 100, the Secondary Attack Rate was 1.1% (95% CI: 1.0%, 1.2% for both vaccine and non-vaccine serotypes. Conclusion This study supports that, in 3–6 years old children, no competitive advantage exists for vaccine serotypes compared to non-vaccine serotypes. This is an argument in favour of important serotype replacement. It would be important to validate the result for infants, who are known to be the main reservoir in maintaining transmission. Overall reduction in pathogenicity should also be taken into account in forecasting the future burden of pneumococcal colonization in vaccinated populations.

  7. 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

    International Nuclear Information System (INIS)

    May, J.C.; Rey, L.; Lee, C.-J.; Arciniega, Juan

    2004-01-01

    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

  8. 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

    Energy Technology Data Exchange (ETDEWEB)

    May, J.C. E-mail: may@cber.fda.gov; Rey, L. E-mail: louis.rey@bluewin.ch; Lee, C.-J.; Arciniega, Juan

    2004-10-01

    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.

  9. Safety, tolerability, and immunogenicity of 15-valent pneumococcal conjugate vaccine in healthy adults.

    Science.gov (United States)

    McFetridge, Richard; Meulen, Ajoke Sobanjo-Ter; Folkerth, Steven D; Hoekstra, John A; Dallas, Michael; Hoover, Patricia A; Marchese, Rocio D; Zacholski, Donna M; Watson, Wendy J; Stek, Jon E; Hartzel, Jonathan S; Musey, Luwy K

    2015-06-04

    Pneumococcal disease remains an important health priority despite successful implementation of pneumococcal conjugate vaccines (PCVs) in infant immunization programs, mainly due to the emergence of diseases caused by serotypes not included in licensed PCVs. A 15-valent pneumococcal conjugate vaccine (PCV-15) containing the 7 serotypes (4, 6B, 9V, 14, 18C, 19F, and 23F) included in licensed PCV-7 available at study initiation plus 8 additional serotypes (1, 3, 5, 6A, 7F, 19A, 22F, 33F) was developed and evaluated in healthy adults 18-45 years of age. Sixty subjects received one dose of PCV-15 or PCV-7. Injection-site and systemic adverse events (AEs) were collected for 14-days postvaccination and serious AEs were collected for 30-days postvaccination. Safety laboratory tests (hematology, chemistry, and urinalysis) were evaluated prior to vaccination and 14-days postvaccination. Serotype-specific IgG and opsonophagocytic killing activity (OPA) responses to 15 serotypes included in PCV-15 were measured immediately prior to vaccination and 30-days postvaccination. AE incidences were comparable between vaccine groups although numerically higher frequencies of erythema (33.3% versus 13.3%), swelling (50.0% versus 23.3%), and myalgia (63.3% versus 36.7%) were reported among PCV-15 versus PCV-7 recipients. Majority of AEs, irrespective of vaccine received, were transient and of mild-to-moderate intensity. No clinically significant differences were observed when comparing AE duration and severity. No laboratory abnormalities, vaccine-related SAEs or discontinuations from the study due to AEs were reported. IgG concentrations for the shared serotypes substantially increased postvaccination at comparable levels between recipients of PCV-15 and PCV-7. Substantial increases in antibody (IgG and OPA) responses to 8 serotypes unique to PCV-15 were observed in PCV-15 recipients. Slight increases to 2 serotypes unique to PCV-15, serotypes 6A and 19A, were also noted in PCV-7

  10. Selective Effects of a Morphine Conjugate Vaccine on Heroin and Metabolite Distribution and Heroin-Induced Behaviors in Rats

    Science.gov (United States)

    Pravetoni, M.; Harris, A.C.; Birnbaum, A.K.; Pentel, P.R.

    2013-01-01

    Morphine conjugate vaccines have effectively reduced behavioral effects of heroin in rodents and primates. To better understand how these effects are mediated, heroin and metabolite distribution studies were performed in rats in the presence and absence of vaccination. In non-vaccinated rats 6-monoacetylmorphine (6-MAM) was the predominant opioid in plasma and brain as early as 1 minute after i.v. administration of heroin and for up to 14 minutes. Vaccination with morphine conjugated to keyhole limpet hemocyanin (M-KLH) elicited high titers and concentrations of antibodies with high affinity for heroin, 6-MAM, and morphine. Four minutes after heroin administration vaccinated rats showed substantial retention of all three opioids in plasma compared to controls and reduced 6-MAM and morphine, but not heroin, distribution to brain. Administration of 6-MAM rather than heroin in M-KLH vaccinated rats showed a similar drug distribution pattern. Vaccination reduced heroin-induced analgesia and blocked heroin-induced locomotor activity throughout 2 weeks of repeated testing. Higher serum opioid-specific antibody concentrations were associated with higher plasma opioid concentrations, lower brain 6-MAM and morphine concentrations, and lower heroin-induced locomotor activity. Serum antibody concentrations over 0.2 mg/ml were associated with substantial effects on these measures. These data support a critical role for 6-MAM in mediating the early effects of i.v. heroin and suggest that reducing 6-MAM concentration in brain is essential to the efficacy of morphine conjugate vaccines. PMID:23220743

  11. Immunogenicity of a combined DTPa-HB vaccine co-administered with Haemophilus influenzae type B conjugate vaccine (PRP-T for primary and booster vaccinations

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    Humberto Bracco Neto

    Full Text Available OBJECTIVE: To evaluate the immunogenicity of a combined DTPa-HB vaccine co-administered with Haemophilus influenzae type b conjugate vaccine (PRP-T in Brazilian infants. MATERIAL AND METHODS: A prospective and open clinical study, in which 110 infants were immunized with a three-dose primary vaccination regime at two, four and six months of age and with a single booster vaccination. Blood samples were drawn immediately before the first dose, one month after the third dose, at the time of the booster dose and one month after the booster to assess seropositivity and antibody geometric mean titers (GMTs of antibodies for diphtheria, tetanus, hepatitis B, Haemophilus influenzae type b and for the three pertussis antigens: Pertussis Toxin (PT, Filamentous Hemagglutinin (FHA and Pertactin (PRN. RESULTS: Among the original 110 infants, 93 completed the study. Seropositivity was 100% for all seven involved antibodies, after the primary vaccination course. At the time of the booster dose, all antibodies (except diphtheria 33.7% and anti-PT 59% were seropositive for more than 94% of subjects. After the booster, seropositivity increased to 100% for all antibodies. The GMT of these antibodies followed a similar pattern, with a strong increase after the primary course, followed by a second increase after the booster dose. At this time, GMT was2- to 7-fold higher than after the primary course, for all vaccine components. CONCLUSIONS: Concomitant administration of DTPa-HB and Hib vaccines elicited strong seroprotection for all the antigenic components. No interference with antibody response was evident. The vaccines provided high immunogenicity, following both the primary vaccinations and the booster dose.

  12. Direct effect of 10-valent conjugate pneumococcal vaccination on pneumococcal carriage in children Brazil.

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    Ana Lucia Andrade

    Full Text Available BACKGROUND: 10-valent conjugate pneumococcal vaccine/PCV10 was introduced in the Brazilian National Immunization Program along the year of 2010. We assessed the direct effectiveness of PCV10 vaccination in preventing nasopharyngeal/NP pneumococcal carriage in infants. METHODS: A cross-sectional population-based household survey was conducted in Goiania Brazil, from December/2010-February/2011 targeting children aged 7-11 m and 15-18 m. Participants were selected using a systematic sampling. NP swabs, demographic data, and vaccination status were collected from 1,287 children during home visits. Main outcome and exposure of interest were PCV10 vaccine-type carriage and dosing schedules (3p+0, 2p+0, and one catch-up dose, respectively. Pneumococcal carriage was defined by a positive culture and serotyping was performed by Quellung reaction. Rate ratio/RR was calculated as the ratio between the prevalence of vaccine-types carriage in children exposed to different schedules and unvaccinated for PCV10. Adjusted RR was estimated using Poisson regression. PCV10 effectiveness/VE on vaccine-type carriage was calculated as 1-RR*100. RESULTS: The prevalence of pneumococcal carriage was 41.0% (95%CI: 38.4-43.7. Serotypes covered by PCV10 and PCV13 were 35.2% and 53.0%, respectively. Vaccine serotypes 6B (11.6%, 23F (7.8%, 14 (6.8%, and 19F (6.6% were the most frequently observed. After adjusted for confounders, children who had received 2p+0 or 3p+0 dosing schedule presented a significant reduction in pneumococcal vaccine-type carriage, with PCV10 VE equal to 35.9% (95%CI: 4.2-57.1; p = 0.030 and 44.0% (95%CI: 14.-63.5; p = 0.008, respectively, when compared with unvaccinated children. For children who received one catch-up dose, no significant VE was detected (p = 0.905. CONCLUSION: PCV10 was associated with high protection against vaccine-type carriage with 2p+0 and 3p+0 doses for children vaccinated before the second semester of life. The continuous

  13. Impact of meningococcal C conjugate vaccination four years after introduction of routine childhood immunization in Brazil.

    Science.gov (United States)

    Andrade, Ana Lucia; Minamisava, Ruth; Tomich, Lisia Moura; Lemos, Ana Paula; Gorla, Maria Cecilia; de Cunto Brandileone, Maria Cristina; Domingues, Carla Madga S; de Moraes, Camile; Policena, Gabriela; Bierrenbach, Ana Luiza

    2017-04-11

    Routine infant immunization with meningococcal C conjugate (MCC) vaccination started in Brazil in November 2010, scheduled at three and five months plus a booster at 12-15months of age. No catch-up was implemented. We assessed the impact of vaccination on meningococcal C disease (MenC) four years after vaccination start in the National Immunization Program. We performed an ecological quasi-experimental design from 2008 to 2014 using a deterministic linkage between the National Notification and the National Reference Laboratory databases for meningitis. We conducted an interrupted time-series analysis considering Brazil except for Salvador municipality, because an epidemic of serogroup C disease occurred in this city, which prompted a mass vaccination campaign with catch-up for adolescents in 2010. Observed MenC rates in the post-vaccination period were compared to expected rates calculated from the pre-vaccination years. Results for Salvador were presented as descriptive data. An additional time-series analysis was performed for the state of São Paulo. A total of 18,136 MenC cases were analyzed. The highest incidence rates were observed for infants aged Brazil, MenC rates were reduced by 67.2% (95%CI 43.0-91.4%) for infants Brazil in individuals aged Brazil. After four years of infants and toddlers vaccination start, MenC invasive disease reduced in the target population. This investigation provide a robust baseline to ascertain how much the upcoming catch-up dose in 12-13years of age will accelerate the decrease in MenC incidence rates among youths in Brazil. Copyright © 2017. Published by Elsevier Ltd.

  14. Post-introduction economic evaluation of pneumococcal conjugate vaccination in Ecuador, Honduras, and Paraguay.

    Science.gov (United States)

    Constenla, Dagna O

    2015-11-01

    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.

  15. Cost-effectiveness of the CRM-based 7-valent pneumococcal conjugated vaccine (PCV7) in Argentina.

    Science.gov (United States)

    Giglio, Norberto D; Cane, Alejandro D; Micone, Paula; Gentile, Angela

    2010-03-08

    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.

  16. Evaluation of impact of 23 valent pneumococcal polysaccharide vaccine following 7 valent pneumococcal conjugate vaccine in Australian Indigenous children.

    Science.gov (United States)

    Jayasinghe, Sanjay; Chiu, Clayton; Menzies, Rob; Lehmann, Deborah; Cook, Heather; Giele, Carolien; Krause, Vicki; McIntyre, Peter

    2015-11-27

    High incidence and serotype diversity of invasive pneumococcal disease (IPD) in Indigenous children in remote Australia led to rapid introduction of 7-valent conjugate pneumococcal vaccine (7vPCV) at 2, 4 and 6 months in 2001, followed by 23-valent polysaccharide pneumococcal vaccine (23vPPV) in the second year of life. All other Australian children were offered 3 doses of 7vPCV without a booster from 2005. This study evaluated the impact of the unique pneumococcal vaccine schedule of 7vPCV followed by the 23vPPV booster among Indigenous Australian children. Changes in IPD incidence derived from population-based passive laboratory surveillance in Indigenous children vaccine introduction period (Indigenous 1994-2000; non-Indigenous 2002-2004) to the post-vaccine period (2008-2010 in both groups) using incidence rate ratios (IRRs) stratified by age into serotype groupings of vaccine (7v and 13vPCV and 23vPPV) and non-vaccine types. Vaccine coverage was assessed from the Australian Childhood Immunisation Register. At baseline, total IPD incidence per 100,000 was 216 (n=230) in Indigenous versus 55 (n=1993) in non-Indigenous children. In 2008-2010, IRRs for 7vPCV type IPD were 0.03 in both groups, but for 23v-non7v type IPD 1.2 (95% CI 0.8-1.8) in Indigenous versus 3.1 (95% CI 2.5-3.7) in non-Indigenous, difference driven primarily by serotype 19A IPD (IRR 0.6 in Indigenous versus 4.3 in non-Indigenous). For non-7vPCV type IPD overall, IRR was significantly higher in those age-eligible for 23vPPV booster compared to those younger, but in both age groups was lower than for non-Indigenous children. These ecologic data suggest a possible "serotype replacement sparing" effect of 23vPPV following 7vPCV priming, especially for serotype 19A with supportive evidence from other immunogenicity and carriage studies. Applicability post 10vPCV or 13v PCV priming in similar settings would depend on local serotype distribution of IPD. Copyright © 2015 Elsevier Ltd. All rights

  17. Risk factors for pneumococcal nasopharyngeal colonization before and after pneumococcal conjugate vaccination in persons with HIV

    DEFF Research Database (Denmark)

    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...... (23%) were colonized, 11 at baseline only, four at both baseline and 9 months, and seven at 9 months only. Compared to non-colonized patients, more colonized patients were smokers, had lower CD4+ nadir and had an AIDS-diagnosis. Immunization, antiretroviral treatment and the CPG adjuvant had no impact...... on colonization. These results suggest preventive strategies in addition to pneumococcal immunization....

  18. Changes in empyema among U.S. children in the pneumococcal conjugate vaccine era.

    Science.gov (United States)

    Wiese, Andrew D; Griffin, Marie R; Zhu, Yuwei; Mitchel, Edward F; Grijalva, Carlos G

    2016-12-07

    Parapneumonic empyema, a serious complication of pneumonia, started increasing among U.S. children before the introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in 2000, and continued afterwards. This increase was due in part to pneumococcal serotypes not included in PCV7 that were included in the new 13-valent (PCV13) vaccine introduced in 2010. We assessed changes in the incidence of empyema hospitalizations among U.S. children after PCV13 introduction. We calculated annualized empyema hospitalization rates among U.S. children children children children 2-4 and 5-17years were similar. Most empyema were of unspecified etiology. Pneumococcal and unspecified empyema declined after PCV13 introduction. Although empyema hospitalization rates among U.S. children peaked after PCV7 introduction, rates decreased substantially following the introduction of PCV13. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Automated capillary Western dot blot method for the identity of a 15-valent pneumococcal conjugate vaccine.

    Science.gov (United States)

    Hamm, Melissa; Ha, Sha; Rustandi, Richard R

    2015-06-01

    Simple Western is a new technology that allows for the separation, blotting, and detection of proteins similar to a traditional Western except in a capillary format. Traditionally, identity assays for biological products are performed using either an enzyme-linked immunosorbent assay (ELISA) or a manual dot blot Western. Both techniques are usually very tedious, labor-intensive, and complicated for multivalent vaccines, and they can be difficult to transfer to other laboratories. An advantage this capillary Western technique has over the traditional manual dot blot Western method is the speed and the automation of electrophoresis separation, blotting, and detection steps performed in 96 capillaries. This article describes details of the development of an automated identity assay for a 15-valent pneumococcal conjugate vaccine, PCV15-CRM197, using capillary Western technology. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Late Onset of Injection Site Reactions After Vaccination With the 13-Valent Pneumococcal Conjugate Vaccine in Adult Study Populations.

    Science.gov (United States)

    Juergens, Christine; Trammel, James; Shoji, Yasuko; Patterson, Scott; Watson, Wendy; Webber, Chris; Gruber, William C; Scott, Daniel A; Schmoele-Thoma, Beate

    2018-03-15

    Injection site reactions (ISRs; redness, swelling and pain) commonly occur within 1-2 days after vaccination. After administration of toxoid vaccines including diphtheria toxoid, a later onset of ISRs has also been observed. As the serotype capsular polysaccharides in the 13-valent pneumococcal conjugate vaccine (PCV13) are conjugated to cross-reactive material 197 (CRM 197 ), a nontoxic variant of diphtheria toxin, the onset of ISRs over 14 days was explored in 8 adult studies with 19 cohorts. Subjects received PCV13 with aluminum phosphate (AlPO 4 , n = 5667) or without AlPO 4 (n = 304); 109 subjects received 23-valent pneumococcal polysaccharide vaccine (PPSV23). Late ISRs with onset between days 6-14 were observed in 8/8 cohorts aged ≥65 years after PCV13 with AlPO 4 (incidence across cohorts for redness, 2.3%-19.6%; swelling, 0.9%-10.8%; pain, 1.6%-10.0%) and in 1/1 cohort after PCV13 without AlPO 4 (redness 10.5%; swelling 7.5%; pain 12.3%); and in 2/4 cohorts aged 50 to 64 years after PCV13 (redness 3.1%-4.8%; swelling 1.0%-3.2%; pain 3.7%-5%). Late ISRs were not generally observed in 1/1 cohort aged 18 to 49 years after PCV13; in 2/2 cohorts aged ≥53 years after PCV13 revaccination; and in 3/3 cohorts aged ≥60 years who received PPSV23, which does not contain CRM 197 . Post hoc analysis demonstrated numerically higher pneumococcal immune responses in subgroups with late ISRs versus those without. In conclusion, causality of late ISRs is likely multifactorial, with age and the PCV13 carrier protein CRM 197 potentially associated. AlPO 4 , a vaccine adjuvant, did not appear causally related. Observations do not affect the favorable risk-benefit profile of PCV13.

  1. Prescreening of Nicotine Hapten Linkers in Vitro To Select Hapten-Conjugate Vaccine Candidates for Pharmacokinetic Evaluation in Vivo.

    Science.gov (United States)

    Arutla, Viswanath; Leal, Joseph; Liu, Xiaowei; Sokalingam, Sriram; Raleigh, Michael; Adaralegbe, Adejimi; Liu, Li; Pentel, Paul R; Hecht, Sidney M; Chang, Yung

    2017-05-08

    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

  2. Immunogenicity and safety of 13-valent pneumococcal conjugate vaccine in Mexico

    Directory of Open Access Journals (Sweden)

    Maricruz Gutiérrez Brito

    2013-06-01

    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.

  3. A forecast of typhoid conjugate vaccine introduction and demand in typhoid endemic low- and middle-income countries to support vaccine introduction policy and decisions.

    Science.gov (United States)

    Mogasale, Vittal; Ramani, Enusa; Park, Il Yeon; Lee, Jung Seok

    2017-09-02

    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.

  4. Cost-effectiveness of 13-valent pneumococcal conjugate vaccination in Mongolia.

    Science.gov (United States)

    Sundaram, Neisha; Chen, Cynthia; Yoong, Joanne; Luvsan, Munkh-Erdene; Fox, Kimberley; Sarankhuu, Amarzaya; La Vincente, Sophie; Jit, Mark

    2017-02-15

    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

  5. Neonatal and Infantile Immune Responses to Encapsulated Bacteria and Conjugate Vaccines

    Directory of Open Access Journals (Sweden)

    Peter Klein Klouwenberg

    2008-01-01

    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.

  6. Determination of saccharide content in pneumococcal polysaccharides and conjugate vaccines by GC-MSD.

    Science.gov (United States)

    Kim, John S; Laskowich, Erin R; Arumugham, Rasappa G; Kaiser, Raymond E; MacMichael, Gregory J

    2005-12-15

    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.

  7. 75 FR 48707 - Proposed Vaccine Information Materials for Pneumococcal Conjugate Vaccine and Human...

    Science.gov (United States)

    2010-08-11

    ... is an infection of the covering of the brain.) Although pneumococcal meningitis is relatively rare.... Pneumococcal meningitis can also lead to other health problems, including deafness and brain damage. Before... vaccination can help prevent fainting and injuries caused by falls. Tell your provider if the patient feels...

  8. Protecting the Herd: The Remarkable Effectiveness of the Bacterial Meningitis Polysaccharide-Protein Conjugate Vaccines in Altering Transmission Dynamics

    OpenAIRE

    Stephens, David S.

    2011-01-01

    Interrupting human-to-human transmission of the agents (Neisseria meningitidis, Haemophilus influenzae, and Streptococcus pneumoniae) of bacterial meningitis by new capsular polysaccharide-protein conjugate vaccines (PPCVs) has proven to be a remarkable (and unanticipated) contributor to vaccine effectiveness. Herd immunity accounts for ∼50% of the protection by meningococcal serogroup C PPCVs, pneumococcal PPCV7, and H. influenzae b PPCVs. Nasopharyngeal carriage can be reduced ≥75% for vacc...

  9. Fluoroquinolone-nonsusceptible Streptococcus pneumoniae isolates from a medical center in the pneumococcal conjugate vaccine era

    Directory of Open Access Journals (Sweden)

    Hsin-Hang Chen

    2017-12-01

    Full Text Available Background/Purpose: Streptococcus pneumoniae is one of the most common pathogens to cause mucosal and invasive infection in humans. Resistance to fluoroquinolones (FQ is associated with clinical failure when treating pneumococcal diseases and increase of mortality. Methods: We collected clinical isolates of S. pneumoniae from January 2011 to July 2015 at Chang Gung Memorial Hospital, Taoyuan, Taiwan. Susceptibility to FQ was examined by disk diffusion method. Levofloxacin or moxifloxacin-nonsusceptible S. pneumoniae isolates were analyzed by serotyping, multilocus sequence typing, and sequencing of the quinolone resistance-determining regions (QRDRs of gyrA, gyrB, parC, and parE. Results: During the study period, 42 FQ-nonsusceptible pneumococcal isolates were identified. The rate increased from 1.6% of total pneumococcal isolates (2 of 127 in 2011 to 4.6% (13 of 283 in 2014, then decreased to 1.5% (3 of 202 in the first half of 2015. These isolates belonged to 13 serotypes, and serotype 14 (12 of 42, 33.3% was the most prevalent. Most of the isolates belonged to international clones or their variants. After QRDR analysis, there were 19 isolates in five clusters that shared both the same sequence type and QRDR mutation. Conclusions: FQ resistance initially emerged in either vaccine or nonvaccine serotypes. The majority of isolates were international clones or related variants, suggesting that resistance was disseminated through clonal spread. The wide use of pneumococcal conjugate vaccine since 2013 appears to have reduced the spread of FQ-nonsusceptible pneumococci. Keywords: Fluoroquinolone, resistance, Streptococcus pneumoniae, pneumococcal conjugate vaccine

  10. Effectiveness of 7-valent pneumococcal conjugate vaccine against radiologically diagnosed pneumonia in indigenous infants in Australia.

    Science.gov (United States)

    O'Grady, K F; Carlin, J B; Chang, A B; Torzillo, P J; Nolan, T M; Ruben, A; Andrews, R M

    2010-02-01

    To evaluate the effectiveness of the 7-valent pneumococcal conjugate vaccine (PCV7) in preventing pneumonia, diagnosed radiologically according to World Health Organization (WHO) criteria, among indigenous infants in the Northern Territory of Australia. We conducted a historical cohort study of consecutive indigenous birth cohorts between 1 April 1998 and 28 February 2005. Children were followed up to 18 months of age. The PCV7 programme commenced on 1 June 2001. All chest X-rays taken within 3 days of any hospitalization were assessed. The primary endpoint was a first episode of WHO-defined pneumonia requiring hospitalization. Cox proportional hazards models were used to compare disease incidence. There were 526 pneumonia events among 10,600 children - an incidence of 3.3 per 1000 child-months; 183 episodes (34.8%) occurred before 5 months of age and 247 (47.0%) by 7 months. Of the children studied, 27% had received 3 doses of vaccine by 7 months of age. Hazard ratios for endpoint pneumonia were 1.01 for 1 versus 0 doses; 1.03 for 2 versus 0 doses; and 0.84 for 3 versus 0 doses. There was limited evidence that PCV7 reduced the incidence of radiologically confirmed pneumonia among Northern Territory indigenous infants, although there was a non-significant trend towards an effect after receipt of the third dose. These findings might be explained by lack of timely vaccination and/or occurrence of disease at an early age. Additionally, the relative contribution of vaccine-type pneumococcus to severe pneumonia in a setting where multiple other pathogens are prevalent may differ with respect to other settings where vaccine efficacy has been clearly established.

  11. The Global Evolution of Meningococcal Epidemiology Following the Introduction of Meningococcal Vaccines.

    Science.gov (United States)

    Pelton, Stephen I

    2016-08-01

    Invasive meningococcal disease (IMD) caused by Neisseria meningitidis is associated with high morbidity and mortality. Although IMD incidence is highest in infants, a second peak occurs in adolescents/young adults. The incidence of IMD and the predominant disease-causing meningococcal serogroups vary worldwide. Epidemiologic data have guided the development of meningococcal vaccines to reduce the IMD burden. In Europe, serogroup C IMD has been substantially reduced since the introduction of a serogroup C conjugate vaccine. Serogroup B predominates in Europe, although cases of serogroup Y IMD have been increasing in recent years. In the United States, declines in serogroup C and Y disease have been observed in association with the introduction of quadrivalent (serogroups ACWY) meningococcal conjugate vaccines; serogroup B persists and is now the most common cause of outbreak associated disease. In the African meningitis belt, a conjugate vaccine for serogroup A has been effective in decreasing meningitis associated with that serogroup. Outbreaks of the previously rare serogroup X disease have been reported in this region since 2006. In recent years, outbreaks of serogroup B IMD, for which vaccines have only recently been approved by the U.S. Food and Drug Administration and the European Medicines Agency, have occurred in Europe and the United States. Targeting meningococcal vaccination to adolescents/young adults may reduce the morbidity and mortality associated with IMD and has the potential to impact the larger community through herd benefits. Copyright © 2016 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

  12. Serogroup A meningococcal conjugate vaccination in Burkina Faso: analysis of national surveillance data.

    Science.gov (United States)

    Novak, Ryan T; Kambou, Jean Ludovic; Diomandé, Fabien Vk; Tarbangdo, Tiga F; Ouédraogo-Traoré, Rasmata; Sangaré, Lassana; Lingani, Clement; Martin, Stacey W; Hatcher, Cynthia; Mayer, Leonard W; Laforce, F Marc; Avokey, Fenella; Djingarey, Mamoudou H; Messonnier, Nancy E; Tiendrébéogo, Sylvestre R; Clark, Thomas A

    2012-10-01

    An affordable, highly immunogenic Neisseria meningitidis serogroup A meningococcal conjugate vaccine (PsA-TT) was licensed for use in sub-Saharan Africa in 2009. In 2010, Burkina Faso became the first country to implement a national prevention campaign, vaccinating 11·4 million people aged 1-29 years. We analysed national surveillance data around PsA-TT introduction to investigate the early effect of the vaccine on meningitis incidence and epidemics. We examined national population-based meningitis surveillance data from Burkina Faso using two sources, one with cases and deaths aggregated at the district level from 1997 to 2011, and the other enhanced with results of cerebrospinal fluid examination and laboratory testing from 2007 to 2011. We compared mortality rates and incidence of suspected meningitis, probable meningococcal meningitis by age, and serogroup-specific meningococcal disease before and during the first year after PsA-TT implementation. We assessed the risk of meningitis disease and death between years. During the 14 year period before PsA-TT introduction, Burkina Faso had 148 603 cases of suspected meningitis with 17 965 deaths, and 174 district-level epidemics. After vaccine introduction, there was a 71% decline in risk of meningitis (hazard ratio 0·29, 95% CI 0·28-0·30, p<0·0001) and a 64% decline in risk of fatal meningitis (0·36, 0·33-0·40, p<0·0001). We identified a statistically significant decline in risk of probable meningococcal meningitis across the age group targeted for vaccination (62%, cumulative incidence ratio [CIR] 0·38, 95% CI 0·31-0·45, p<0·0001), and among children aged less than 1 year (54%, 0·46, 0·24-0·86, p=0·02) and people aged 30 years and older (55%, 0·45, 0·22-0·91, p=0·003) who were ineligible for vaccination. No cases of serogroup A meningococcal meningitis occurred among vaccinated individuals, and epidemics were eliminated. The incidence of laboratory-confirmed serogroup A N meningitidis dropped

  13. Development of a peptide conjugate vaccine for inducing therapeutic anti-IgE antibodies.

    Science.gov (United States)

    Licari, Amelia; Castagnoli, Riccardo; De Sando, Elisabetta; Marseglia, Gian Luigi

    2017-04-01

    Given the multifaceted effector functions of IgE in immediate hypersensitivity, late-phase reactions, regulation of IgE receptor expression and immune modulation, IgE antibodies have long represented an attractive target for therapeutic agents in asthma and other allergic diseases. Effective pharmacologic blockade of the binding of IgE to its receptors has become one of most innovative therapeutic strategies in the field of allergic diseases in the last 10 years. Areas covered: The latest strategies targeting IgE include the development of a therapeutic vaccine, able to trigger our own immune systems to produce therapeutic anti-IgE antibodies, potentially providing a further step forward in the treatment of allergic diseases. The aim of this review is to discuss the discovery strategy, preclinical and early clinical development of a peptide conjugate vaccine for inducing therapeutic anti-IgE antibodies. Expert opinion: Outside the area of development of humanized anti-IgE monoclonal antibodies, the research field of therapeutic IgE-targeted vaccines holds potential benefits for the treatment of allergic diseases. However, most of the experimental observations in animal models have not yet been translated into new treatments and evidence of human efficacy and safety of this new therapeutic strategy are still lacking.

  14. Treatment with belimumab in systemic lupus erythematosus does not impair antibody response to 13-valent pneumococcal conjugate vaccine.

    Science.gov (United States)

    Nagel, J; Saxne, T; Geborek, P; Bengtsson, A A; Jacobsen, S; Svaerke Joergensen, C; Nilsson, J-Å; Skattum, L; Jönsen, A; Kapetanovic, M C

    2017-09-01

    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

  15. Adverse reactions to simultaneous influenza and pneumococcal conjugate vaccinations in children : randomized double-blind controlled trial

    NARCIS (Netherlands)

    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

  16. The effect of immunization with pneumococcal conjugated vaccines on Streptococcus pneumoniae resistance patterns in acute otitis media

    Directory of Open Access Journals (Sweden)

    Tal Marom

    2017-10-01

    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.

  17. Estimated effect of pneumococcal conjugate vaccination on invasive pneumococcal disease and associated mortality, Denmark 2000-2005

    DEFF Research Database (Denmark)

    Harboe, Zitta B; Valentiner-Branth, Palle; Benfield, Thomas

    2008-01-01

    In order to provide an estimation of the direct and indirect benefits of pneumococcal vaccination with three protein-conjugate pneumococcal vaccines (PCV) we described the epidemiology and mortality from invasive pneumococcal disease (IPD) in Denmark between 2000 and 2005. Approximately 1080 cases......% to 91% depending on the PCV used. The mean mortality proportion after IPD was 18%, with approximately 190 deaths annually. One to two deaths among children younger than 5 years and approximately 50 deaths related to IPD caused by vaccine serotypes among older age groups could be prevented annually...

  18. Effects of Infant Pneumococcal Conjugate Vaccination on Serotype Distribution in Invasive Pneumococcal Disease among Children and Adults in Germany.

    Science.gov (United States)

    van der Linden, Mark; Falkenhorst, Gerhard; Perniciaro, Stephanie; Imöhl, Matthias

    2015-01-01

    This study describes the effects of the introduction of universal infant pneumococcal conjugate vaccination in 2006 on invasive pneumococcal disease (IPD) among children and adults in Germany with a focus on the dynamics of serotype distribution in vaccinated and non-vaccinated age groups. Over a period of 22 years (1992-2014), microbiological diagnostic laboratories from all over Germany have been sending isolates of IPD cases to the German National Reference Center for Streptococci on a voluntary basis. Streptococcus pneumoniae isolates were serotyped using Neufeld's Quellung method. Among children vaccination (1997-2006) to 23.5% in the early vaccination period (2007-2010; p = 1.30E-72) and sank further to 5.2% in the late vaccination period (2010-2014; p = 4.59E-25). Similar reductions were seen for the separate age groups vaccination period (1992-2006) to 24.7% (p = 3.78E-88) in the early vaccination period and 8.2% (p = 5.97E-161) in the late vaccination period. Both among children and among adults, the non-PCV7 serotypes 1, 3, 7F and 19A significantly increased in the early vaccination period. After the switch from PCV7 to PVC10/PCV13 for infant vaccination in 2010, serotypes 1, 6A and 7F significantly decreased. A decrease in serotype 19A was only observed in 2013-2014, as compared to 2010-2011 (children p = 4.16E-04, adults p = 6.98E-06). Among adults, serotype 3, which strongly increased in the early vaccination period (p = 4.44E-15), remained at a constant proportion in the late vaccination period. The proportion of non-PCV13 vaccine serotypes increased over the whole vaccination period, with serotypes 10A, 12F, 23B, 24F and 38 most significantly increasing among children and serotypes 6C, 12F, 15A, 22F and 23B increasing among adults. Eight years of childhood pneumococcal conjugate vaccination have had a strong effect on the pneumococcal population in Germany, both among the target group for vaccination as well as among older children and adults.

  19. Immunogenicity of a reduced schedule of meningococcal group C conjugate vaccine given concomitantly with the Prevenar and Pediacel vaccines in healthy infants in the United Kingdom.

    Science.gov (United States)

    Southern, Jo; Borrow, Ray; Andrews, Nick; Morris, Rhonwen; Waight, Pauline; Hudson, Michael; Balmer, Paul; Findlow, Helen; Findlow, Jamie; Miller, Elizabeth

    2009-02-01

    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.

  20. Impact of the antipneumococcal conjugate vaccine on the occurrence of infectious respiratory diseases and hospitalization rates in children

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    Wanderci Marys Oliveira Abrão

    2015-02-01

    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.

  1. Empyema due to Streptococcus Pneumoniae Serotype 9V in a Child Immunized with 13-Valent Conjugated Pneumococcal Vaccine

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    Murat Sütçü

    2017-02-01

    Full Text Available Background: Clinical vaccine failure is the occurence of the specific vaccine-preventable disease in an appropriately and fully vaccinated person after enough time has elapsed for protection against the antigens of the vaccine to develop. Fully immunized cases with pneumoccal vaccine may sometimes develop a complicated pneumonia with empyema caused by a vaccine serotype. Case Report: A 2 year-old male patient was admitted with the complaints of fever. On the basis of findings and laboratory results, the patient was diagnosed as having empyema. He was successfully treated with parenteral antibiotics and chest tube drainage. The pleural fluid culture and hemoculture of the patient yielded penicillin-susceptible pneumococci and the isolate was identified as serotype 9V. The patient had been vaccinated with a 13-valent pneumococcal conjugate vaccine according to the Turkish national immunization schedule at 2, 4, 6 and 12 months of age. His medical history and basic immunological profile were inconsistent with a primary immunodeficiency. Conclusion: The failure of the PCV13 vaccine may results in a complicated pneumonia with empyema. It is important to investigate serotypes of pneumococci in these cases to determine other possible vaccine failures due to PCV13 and to study the underlying mechanisms

  2. Optimising assessments of the epidemiological impact in the Netherlands of paediatric immunisation with 13-valent pneumococcal conjugate vaccine using dynamic transmission modelling

    NARCIS (Netherlands)

    De Cao, Elisabetta; Melegaro, Alessia; Klok, Rogier; Postma, Maarten

    2014-01-01

    This work is the first attempt to quantify the overall effects of a 13-valent pneumococcal conjugate vaccine (PCV13) vaccination programme in the Dutch population taking into account all the direct and indirect effects of the vaccine on invasive pneumococcal disease. Using available Dutch data, a

  3. The effect of a pneumococcal conjugate vaccine on the risk of otitis media with effusion at 7 and 24 months of age.

    NARCIS (Netherlands)

    Straetemans, M.; Palmu, A.; Auranen, K.; Zielhuis, G.A.; Kilpi, T.

    2003-01-01

    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

  4. Cost-effectiveness of heptavalent conjugate pneumococcal vaccine (Prevenar) in Germany: considering a high-risk population and herd immunity effects.

    Science.gov (United States)

    Lloyd, Adam; Patel, Nishma; Scott, David A; Runge, Claus; Claes, Christa; Rose, Markus

    2008-02-01

    In Germany, the seven-valent conjugate vaccine Prevenar is recommended for use in children at high risk of pneumococcal disease. Recent data suggest that giving conjugate vaccine to all children may lead to a decline in pneumococcal disease in unvaccinated adults, a phenomenon known as herd immunity. This analysis evaluated the cost and economic consequences in Germany of vaccinating (1) children at high risk, (2) all children when considering only benefits for vaccinated individuals and (3) all children when also considering herd immunity benefits. Costs in the model included vaccination, management of meningitis, bacteraemia, pneumonia and acute otitis media, insurance payments to parents and the costs of care for long-term disabilities. The model estimated that the cost-effectiveness of vaccination would be 38,222 euros per life year gained in children at high risk and 100,636 euros per life year gained in all children when not considering herd immunity. When considering herd immunity effects, the model estimated that offering vaccination for all children would reduce adult deaths by 3,027 per year, and vaccination would be broadly cost neutral. The findings are sensitive to the effect of conjugate vaccine on the rates of pneumonia and invasive disease in the elderly. If the herd immunity effect of conjugate vaccination in Germany is similar to that observed elsewhere, offering vaccine to all children will be more attractive than the current policy of restricting vaccination to children at high risk of pneumococcal disease.

  5. 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

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    Leyla S. Namazova-Baranova

    2017-01-01

    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.

  6. TLR7/8 adjuvant overcomes newborn hyporesponsiveness to pneumococcal conjugate vaccine at birth

    Science.gov (United States)

    Dowling, David J.; van Haren, Simon D.; Scheid, Annette; Bergelson, Ilana; Kim, Dhohyung; Mancuso, Christy J.; Foppen, Willemina; Fresh, Lynn; Theriot, Terese B.; Lackner, Andrew A.; Fichorova, Raina N.; Smirnov, Dmitri; Vasilakos, John P.; Beaurline, Joe M.; Tomai, Mark A.; Midkiff, Cecily C.; Alvarez, Xavier; Blanchard, James L.; Gilbert, Margaret H.; Aye, Pyone Pyone

    2017-01-01

    Infection is the most common cause of mortality in early life, and immunization is the most promising biomedical intervention to reduce this burden. However, newborns fail to respond optimally to most vaccines. Adjuvantation is a key approach to enhancing vaccine immunogenicity, but responses of human newborn leukocytes to most candidate adjuvants, including most TLR agonists, are functionally distinct. Herein, we demonstrate that 3M-052 is a locally acting lipidated imidazoquinoline TLR7/8 agonist adjuvant in mice, which, when properly formulated, can induce robust Th1 cytokine production by human newborn leukocytes in vitro, both alone and in synergy with the alum-adjuvanted pneumococcal conjugate vaccine 13 (PCV13). When admixed with PCV13 and administered i.m. on the first day of life to rhesus macaques, 3M-052 dramatically enhanced generation of Th1 CRM-197–specific neonatal CD4+ cells, activation of newborn and infant Streptococcus pneumoniae polysaccharide–specific (PnPS-specific) B cells as well as serotype-specific antibody titers, and opsonophagocytic killing. Remarkably, a single dose at birth of PCV13 plus 0.1 mg/kg 3M-052 induced PnPS-specific IgG responses that were approximately 10–100 times greater than a single birth dose of PCV13 alone, rapidly exceeding the serologic correlate of protection, as early as 28 days of life. This potent immunization strategy, potentially effective with one birth dose, could represent a new paradigm in early life vaccine development. PMID:28352660

  7. [Bacterial etiology of acute otitis media in Spain in the post-pneumococcal conjugate vaccine era].

    Science.gov (United States)

    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

    2016-11-01

    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.

  8. Impact of the serogroup A meningococcal conjugate vaccine, MenAfriVac, on carriage and herd immunity.

    Science.gov (United States)

    Kristiansen, Paul A; Diomandé, Fabien; Ba, Absatou Ky; Sanou, Idrissa; Ouédraogo, Abdoul-Salam; Ouédraogo, Rasmata; Sangaré, Lassana; Kandolo, Denis; Aké, Flavien; Saga, Inger Marie; Clark, Thomas A; Misegades, Lara; Martin, Stacey W; Thomas, Jennifer Dolan; Tiendrebeogo, Sylvestre R; Hassan-King, Musa; Djingarey, Mamoudou H; Messonnier, Nancy E; Préziosi, Marie-Pierre; Laforce, F Marc; Caugant, Dominique A

    2013-02-01

    The conjugate vaccine against serogroup A Neisseria meningitidis (NmA), MenAfriVac, was first introduced in mass vaccination campaigns of 1-29-year-olds in Burkina Faso in 2010. It is not known whether MenAfriVac has an impact on NmA carriage. We conducted a repeated cross-sectional meningococcal carriage study in a representative portion of the 1-29-year-old population in 3 districts in Burkina Faso before and up to 13 months after vaccination. One district was vaccinated in September 2010, and the other 2 were vaccinated in December 2010. We analyzed 25 521 oropharyngeal samples, of which 22 093 were obtained after vaccination. In October-November 2010, NmA carriage prevalence in the unvaccinated districts was comparable to the baseline established in 2009, but absent in the vaccinated district. Serogroup X N. meningitidis (NmX) dominated in both vaccinated and unvaccinated districts. With 4 additional sampling campaigns performed throughout 2011 in the 3 districts, overall postvaccination meningococcal carriage prevalence was 6.95%, with NmX dominating but declining for each campaign (from 8.66% to 1.97%). Compared with a baseline NmA carriage prevalence of 0.39%, no NmA was identified after vaccination. Overall vaccination coverage in the population sampled was 89.7%, declining over time in 1-year-olds (from 87.1% to 26.5%), as unvaccinated infants reached 1 year of age. NmA carriage was eliminated in both the vaccinated and unvaccinated population from 3 weeks up to 13 months after mass vaccination (P = .003). The disappearance of NmA carriage among both vaccinated and unvaccinated populations is consistent with a vaccine-induced herd immunity effect.

  9. Treatment with belimumab in systemic lupus erythematosus does not impair antibody response to 13-valent pneumococcal conjugate vaccine

    DEFF Research Database (Denmark)

    Nagel, J.; Saxne, T.; Geborek, P.

    2017-01-01

    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......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...

  10. Effect of the 13-valent pneumococcal conjugate vaccine on nasopharyngeal carriage by respiratory pathogens among Greenlandic children

    DEFF Research Database (Denmark)

    Navne, Johan Emdal; Koch, Anders; Slotved, Hans-Christian

    2017-01-01

    BACKGROUND: In 2010, Greenland introduced the 13-valent pneumococcal conjugate vaccine (Prevnar 13®- PCV-13) in the childhood immunisation program. The authors aimed to evaluate the impact of PCV-13 on nasopharyngeal carriage of bacteria frequently associated with respiratory infections in children....... 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-vaccine...... types. Carriage rate of S. aureus decreased significantly among vaccinated children whereas that of M. catarrhalis increased. CONCLUSION: PCV-13 introduction in Greenland is associated with significant changes in nasopharyngeal bacterial carriage. Continued surveillance is warranted to clarify whether...

  11. Protecting the herd: the remarkable effectiveness of the bacterial meningitis polysaccharide-protein conjugate vaccines in altering transmission dynamics.

    Science.gov (United States)

    Stephens, David S

    2011-01-01

    Interrupting human-to-human transmission of the agents (Neisseria meningitidis, Haemophilus influenzae, and Streptococcus pneumoniae) of bacterial meningitis by new capsular polysaccharide-protein conjugate vaccines (PPCVs) has proven to be a remarkable (and unanticipated) contributor to vaccine effectiveness. Herd immunity accounts for ∼50% of the protection by meningococcal serogroup C PPCVs, pneumococcal PPCV7, and H. influenzae b PPCVs. Nasopharyngeal carriage can be reduced ≥75% for vaccine serotypes; the decrease in carriage is correlated with disease reduction in unvaccinated individuals, and the impact of herd immunity lasts for years. Based on these data, models for using herd immunity in vaccine-based prevention strategies are underway for control of meningitis in sub-Saharan Africa. Although the immunologic basis of herd immunity and impact on microbial biology need more study, protecting the unvaccinated by altering pathogen transmission dynamics is a powerful effect of PPCVs and increasingly important in vaccine introduction, implementation, and evaluation strategies.

  12. Indirect (herd) protection, following pneumococcal conjugated vaccines introduction: A systematic review of the literature.

    Science.gov (United States)

    Tsaban, Gal; Ben-Shimol, Shalom

    2017-05-19

    Pneumococcal diseases are major causes of morbidity among adults, especially those over 50years of age. While pneumococcal conjugated vaccines (PCV's) impact on pneumococcal disease rates among children is well established, the extent of its impact on adult pneumococcal related illness remains unclear. The aim of this systematic literature review was to describe the impact of PCV introduction to childhood national immunization programs worldwide on PCV-naive adult population. A systematic literature search was performed using the PubMed database. The search was limited to articles written in English and published between January 2000 and February 2016. Studies evaluating pneumococcal disease rates in individuals over 5years of age were included. Independent extraction of articles was performed by the two authors. Search terms included: Pneumococcal conjugated vaccine, herd, indirect, adults, and pneumonia. Forty-nine articles meeting the selection criteria were identified, 39 regarding invasive pneumococcal disease (IPD, one on meningitis only), 8 regarding pneumonia, and 2 on both IPD and pneumonia. The majority of reports were from the US, UK and Canada. Considerable variability in the data sources, quality and completeness was observed. While most studies reported either statistically significant reduction or insignificant changes in IPD and pneumonia disease rates in adults following PCV nationwide implementation, few studies reported statistically significant increase in pneumococcal disease rates, these were mainly from countries with low PCV coverage rates and/or inadequate surveillance. Invasive pneumococcal diseases and pneumonia rates among the adult population decreased in most countries following PCV introduction into the NIP. This indirect effect on older population seems to be dependent on PCV coverage rates and time from PCV nationwide implementation. Adults >65years old seem to benefit the most from PCV introduction. Copyright © 2017 Elsevier Ltd

  13. Can the success of pneumococcal conjugate vaccines for the prevention of pneumococcal diseases in children be extrapolated to adults?

    Science.gov (United States)

    Weil-Olivier, Catherine; Gaillat, Jacques

    2014-04-11

    Before conjugate pneumococcal vaccines (PCVs) were introduced it was estimated that Streptococcus pneumoniae caused 500,000 cases of pneumonia, 50,000 cases of bacteremia and 3000 cases of meningitis annually in the United States in both children and adults. After 10 years of routine use of the 7-valent pneumococcal conjugate vaccine (PCV7) the incidence of vaccine-type pneumococcal diseases (PDs) had significantly decreased in vaccinated children (direct effect) and unvaccinated subjects of all ages (indirect effect). Second generation, higher-valent PCVs, especially 13-valent (PCV13), routinely implemented since 2010, have reduced the incidence of PDs caused by the six additional non-PCV7 serotypes, in both vaccinated and unvaccinated subjects. The licence for this vaccine has recently been extended to include adults aged 18 to 49 in Europe. Although PCV13 has an indirect effect on IPD in adults, this will probably not achieve the same level of disease control in adults and the elderly (especially those at high risk) as that obtained in vaccinated children. As highlighted in this paper, differences exist between children and adults for PD manifestations (incidence, morbidity and mortality) and serotypes isolated in nasopharyngeal carriage and diseases, so benefits from adult vaccination must be considered in this light. PCV13 induces an immune response in adults that is non-inferior for all serotypes common with the 23-valent plain polysaccharide vaccine that is currently recommended for adults and even superior for many serotypes. Although there is no evidence that this immune response translates to clinical efficacy in adults as seen in children, the results from a randomised trial in The Netherlands, expected in 2014, should provide the missing evidence. This evidence and efficient surveillance systems should provide the necessary data, essential for policy makers in their decisions on adult pneumococcal vaccination policies. Copyright © 2014 Elsevier Ltd

  14. Concomitant administration of a fully liquid, ready-to-use DTaP-IPV-HB-PRP-T hexavalent vaccine with a meningococcal serogroup C conjugate vaccine in infants.

    Science.gov (United States)

    Vesikari, Timo; Borrow, Ray; Da Costa, Xavier; Richard, Patrick; Eymin, Cécile; Boisnard, Florence; Lockhart, Stephen

    2017-01-11

    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.

  15. Development of a new trend conjugate vaccine for the prevention of Klebsiella pneumoniae

    Directory of Open Access Journals (Sweden)

    Tarek A. Ahmad

    2012-07-01

    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.

  16. 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

    NARCIS (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.

    2016-01-01

    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

  17. Longitudinal multiparameter single-cell analysis of macaques immunized with pneumococcal protein-conjugated or unconjugated polysaccharide vaccines reveals distinct antigen specific memory B cell repertoires.

    Directory of Open Access Journals (Sweden)

    Bin Jia

    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.

  18. Longitudinal multiparameter single-cell analysis of macaques immunized with pneumococcal protein-conjugated or unconjugated polysaccharide vaccines reveals distinct antigen specific memory B cell repertoires.

    Science.gov (United States)

    Jia, Bin; McNeil, Lisa K; Dupont, Christopher D; Tsioris, Konstantinos; Barry, Rachel M; Scully, Ingrid L; Ogunniyi, Adebola O; Gonzalez, Christopher; Pride, Michael W; Gierahn, Todd M; Liberator, Paul A; Jansen, Kathrin U; Love, J Christopher

    2017-01-01

    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.

  19. Antibody persistence following meningococcal C conjugate vaccination in children and adolescents infected with human immunodeficiency virus

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    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.

  20. Antibody persistence following meningococcal C conjugate vaccination in children and adolescents infected with human immunodeficiency virus.

    Science.gov (United States)

    Frota, Ana Cristina Cisne; Harrison, Lee H; Ferreira, Bianca; Menna-Barreto, Daniela; Castro, Raquel Bernardo Nana de; Silva, Giselle Pereira da; Oliveira, Ricardo Hugo de; Abreu, Thalita F; Milagres, Lucimar G; Hofer, Cristina B

    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. 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. 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. 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. Copyright © 2017. Published by Elsevier Editora Ltda.

  1. Evaluation of a training DVD on pneumococcal conjugate vaccine for Kenyan EPI healthcare workers.

    Science.gov (United States)

    Stokx, Jocelijn; Dochez, Carine; Ochieng, Pamela; Bahl, Jhilmil; Were, Fred

    2016-01-01

    The Kenyan Ministry of Public Health and Sanitation was the first in Africa to introduce the new 10-valent Pneumococcal Conjugate Vaccine, PCV-10, in 2011. For successful implementation and to avoid adverse events following immunisation, specific training on handling and storage of the PCV-10 vaccine was required. Therefore, a training DVD was recorded in English and partly in Kiswahili to be used in combination with in-classroom training. Since the Kenyan Immunisation Programme was the first to use a DVD for training healthcare workers, an evaluation was done to obtain feedback on content, format and use, and propose suggestions to improve quality and uptake of the DVD. Feedback was obtained from nurses and vaccinology course participants through the completion of a questionnaire. Nurses also participated in focus group discussions and trainers in key informant interviews. Twelve trainers, 72 nurses and 26 international vaccinology course participants provided feedback, with some notable differences between the three study groups. The survey results confirmed the acceptability of the content and format, and the feasibility of using the DVD in combination with in-classroom teaching. To improve the quality and adoption of the DVD, key suggestions were: Inclusion of all EPI vaccines and other important health issues; broad geographic distribution of the DVD; and bilingual English/Kiswahili use of languages or subtitles. The Kenyan DVD is appreciated by a heterogeneous and international audience rendering the DVD suitable for other Anglophone African countries. Differences between feedback from nurses and vaccinology course participants can be explained by the practical approach of the DVD and the higher education and service level of the latter. A drawback is the use of DVD players and televisions due to lack of electricity, but it is a matter of time before all rural health facilities in Africa will have access to electricity and modern technology.

  2. Dynamic models of pneumococcal carriage and the impact of the Heptavalent Pneumococcal Conjugate Vaccine on invasive pneumococcal disease

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    Edmunds W John

    2010-04-01

    Full Text Available Abstract Background The 7-valent pneumococcal conjugate vaccine has been introduced in national immunisation programmes of most industrialised countries and recently in two African GAVI eligible countries (Rwanda and The Gambia. However the long term effects of PCV are still unclear, as beneficial direct and herd immunity effects might be countered by serotype replacement. Method A dynamic, age-structured, compartmental model of Streptococcus pneumoniae transmission was developed to predict the potential impact of PCV7 on the incidence of invasive disease accounting for both herd immunity and serotype replacement effects. The model was parameterised using epidemiological data from England and Wales and pre and post-vaccination surveillance data from the US. Results Model projections showed that serotype replacement plays a crucial role in determining the overall effect of a PCV7 vaccination programme and could reduce, negate or outweigh its beneficial impact. However, using the estimate of the competition parameter derived from the US post-vaccination experience, an infant vaccination programme would prevent 39,000 IPD cases in the 20 years after PCV7 introduction in the UK. Adding a catch-up campaign for under 2 or under 5 year olds would provide a further reduction of 1,200 or 3,300 IPD cases respectively, mostly in the first few years of the programme. Conclusions This analysis suggests that a PCV vaccination programme would eradicate vaccine serotypes from circulation. However, the increase in carriage of non-vaccine serotypes, and the consequent increase in invasive disease, could reduce, negate or outweigh the benefit. These results are sensitive to changes in the protective effect of the vaccine, and, most importantly, to the level of competition between vaccine and non-vaccine types. The techniques developed here can be used to assess the introduction of vaccination programmes in developing countries and provide the basis for cost

  3. Influence of initial vaccination with 13-valent pneumococcal conjugate vaccine or 23-valent pneumococcal polysaccharide vaccine on anti-pneumococcal responses following subsequent pneumococcal vaccination in adults 50 years and older.

    Science.gov (United States)

    Jackson, Lisa A; Gurtman, Alejandra; van Cleeff, Martin; Frenck, Robert W; Treanor, John; Jansen, Kathrin U; Scott, Daniel A; Emini, Emilio A; Gruber, William C; Schmoele-Thoma, Beate

    2013-08-02

    Unlike free polysaccharide vaccines, pneumococcal polysaccharide conjugate vaccines (PCVs) induce a T cell-dependent immune response and have the potential to provide an extended duration of protection with repeated vaccinations. This was an extension of a previous study in pneumococcal vaccine-naïve adults aged 50-64 years in which adults 60-64 years of age were given 13-valent PCV (PCV13) or 23-valent pneumococcal polysaccharide vaccine (PPSV23) and adults aged 50-59 were given PCV13. In this follow up study conducted about 4 years later, the 60-64 year olds initially given PCV13 received PCV13 or PPSV23, and those initially given PPSV23 received another PPSV23. All adults aged 50-59 years were re-vaccinated with PCV13. Anti-pneumococcal opsonophagocytic activity (OPA) titers were measured before and 1 month after vaccination. A second PCV13 given about 4 years after a first vaccination induced OPA titers that were significantly higher than those following the initial vaccination for 7 of 13 serotypes in the older group, and 6 of 13 serotypes in the younger group, and responses to the remaining serotypes were largely non-inferior. In contrast, OPA titers following revaccination with PPSV23 were statistically significantly lower for 9 of the 13 serotypes, and non-inferior for the remaining serotypes, when compared to the responses to the first PPSV23. OPA titers in the older adults who received PPSV23 after initial PCV13 were significantly higher than those following a first PPSV23 for 10 of the 13 serotypes. In adults 50 to 64 years of age, initial vaccination with PCV13 establishes an immune state that results in recall anti-pneumococcal responses upon subsequent vaccination with either conjugated or free polysaccharide vaccine. In contrast, initial vaccination with PPSV23 results in an immune state in which subsequent PPSV23 administration yields generally lower responses compared with the initial responses. Copyright © 2013 The Authors. Published by Elsevier

  4. Parental knowledge, attitudes and perception of pneumococcal disease and pneumococcal conjugate vaccines in Singapore: a questionnaire-based assessment

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    Choon How How

    2016-09-01

    Full Text Available Abstract Background Under the National Childhood Immunisation Schedule (NCIS in Singapore most vaccines are provided free while some, including pneumococcal conjugate vaccines (PCV, added to the NCIS in October 2009, are not free. In contrast to ≥95 % coverage achieved for recommended childhood vaccines that are free, 2013 coverage of the PCV booster dose was 58.9 % (for unclear reasons. To date, no population impact on pneumococcal disease (PD has been observed. We conducted a questionnaire-based study of parents of young children to assess the value of PCV to parents, and to quantify the extent to which vaccine cost is a barrier to PCV uptake in Singapore. Methods A single, trained interviewer administered a questionnaire to 200 parents ≥21 years of age with young children attending the Singapore Sengkang Polyclinic. The questionnaire asked closed-ended questions on parents’ knowledge about PD and PCV. A 5-point Likert scale measured perceived benefits and barriers to PCV vaccination. Results There were 162 parents whose children were either PCV-vaccinated or who intended to vaccinate their child with PCV (Vaccinated group, and 38 whose children were non-PCV vaccinated or who did not intend to vaccinate (Unvaccinated group. The odds ratio for PCV vaccination among parents who perceived cost as a barrier was 0.16 (95%CI 0.02–1.23. Compared to the Vaccinated group, parents in the Unvaccinated group were less willing to pay for PCV (50.0 %/94.4 %. Compared to the Vaccinated group, fewer parents in the Unvaccinated group had heard about PD (34.2 %/82.1 % or PCV (36.8 %/69.1 %, or perceived that PD was a threat to their child. Fewer parents in the Unvaccinated group knew that vaccination could prevent PD (28.9 %/77.8 %, or reported that PCV vaccination was recommended to them by any source (63.2 % had no PCV recommendation, versus 20.4 %. When informed that PCV is included in the NCIS only 65.8 % of parents in the Unvaccinated

  5. Serogroup A meningococcal conjugate vaccine coverage after the first national mass immunization campaign-Burkina Faso, 2011.

    Science.gov (United States)

    2012-12-21

    In December 2010, Burkina Faso became the first country to introduce PsA-TT (MenAfriVac), a new serogroup A meningococcal conjugate vaccine developed to eliminate epidemic meningitis in sub-Saharan Africa, via a national mass-immunization campaign. This campaign targeted persons aged 1-29 years, approximately 70% of the 16 million residents of the country. More than 11 million vaccine doses were administered in a 10-day period, for an estimated administrative coverage of 102.6%. Accurate vaccination coverage estimates are critical for programmatic evaluation, identification of undervaccinated subpopulations, and for measurement of the impact of PsA-TT on serogroup A disease and carriage. In December 2011, the Burkina Faso Ministry of Health, in collaboration with CDC, conducted a stratified cluster survey to obtain regional and age-group-specific vaccination coverage estimates among campaign-eligible persons. National coverage was 95.9% (74.3% with vaccination card, 21.6% by recall), and coverage in the 13 regions of Burkina Faso ranged from 90.8% to 98.3%. Coverage was 97.0% in children aged 2-5 years, 97.4% in those aged 6-15 years, and 93.4% in those aged 16-30 years. The results of this survey demonstrate successful introduction of a new vaccine in Burkina Faso through a mass immunization campaign, the first step in a strategy aimed at rapidly interrupting transmission and carriage of serogroup A Neisseria meningitidis before introduction of the vaccine into national routine immunization programs. With phased introduction of PsA-TT planned through 2016 in Africa's "meningitis belt," lessons learned from the Burkina Faso experience will help guide successful introduction of serogroup A meningococcal conjugate vaccine elsewhere.

  6. Impact of Pneumococcal Conjugate Vaccine Administration in Pediatric Older Age Groups in Low and Middle Income Countries: A Systematic Review.

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    Kimberly Bonner

    Full Text Available Pneumococcal conjugate vaccine (PCV is included in the World Health Organization's routine immunization schedule and is recommended by WHO for vaccination in high-risk children up to 60 months. However, many countries do not recommend vaccination in older age groups, nor have donors committed to supporting extended age group vaccination. To better inform decision-making, this systematic review examines the direct impact of extended age group vaccination in children over 12 months in low and middle income countries.An a priori protocol was used. Using pre-specified terms, a search was conducted using PubMed, LILACS, Cochrane Infectious Diseases Group Specialized Register, Cochrane Central Register of Controlled Trials, CAB Abstracts, clinicaltrials.gov and the International Symposium on Pneumococci and Pneumococcal Diseases abstracts. The primary outcome was disease incidence, with antibody titers and nasopharyngeal carriage included as secondary outcomes.Eighteen studies reported on disease incidence, immune response, and nasopharyngeal carriage. PCV administered after 12 months of age led to significant declines in invasive pneumococcal disease. Immune response to vaccine type serotypes was significantly higher for those vaccinated at older ages than the unimmunized at the established 0.2 ug/ml and 0.35 ug/ml thresholds. Vaccination administered after one year of age significantly reduced VT carriage with odds ratios ranging from 0.213 to 0.69 over four years. A GRADE analysis indicated that the studies were of high quality.PCV administration in children over 12 months leads to significant protection. The direct impact of PCV administration, coupled with the large cohort of children missed in first year vaccination, indicates that countries should initiate or expand PCV immunization for extended age group vaccinations. Donors should support implementation of PCV as part of delayed or interrupted immunization for older children. For countries to

  7. Impact of protein D-containing pneumococcal conjugate vaccines on non-typeable Haemophilus influenzae acute otitis media and carriage.

    Science.gov (United States)

    Clarke, Christopher; Bakaletz, Lauren O; Ruiz-Guiñazú, Javier; Borys, Dorota; Mrkvan, Tomas

    2017-07-01

    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.

  8. Influence of Pneumococcal Conjugate Vaccine on Acute Otitis Media with Severe Middle Ear Inflammation: A Retrospective Multicenter Study.

    Science.gov (United States)

    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

    2015-01-01

    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.

  9. Interchangeability of meningococcal group C conjugate vaccines with different carrier proteins in the United Kingdom infant immunisation schedule.

    Science.gov (United States)

    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

    2015-01-29

    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.

  10. Concomitant Adolescent Vaccination in the U.S., 2007-2012.

    Science.gov (United States)

    Moss, Jennifer L; Reiter, Paul L; Brewer, Noel T

    2016-11-01

    Concomitant (same-day) delivery of two or more vaccines to adolescents is effective, safe, and efficient. Increasing concomitant vaccination could improve coverage for recommended adolescent vaccines, but little is known about who receives vaccines concomitantly. Data came from healthcare provider-verified records on 70,144 adolescents (aged 13-17 years) in the 2008-2012 versions of the National Immunization Survey-Teen who had received at least one dose of tetanus, diphtheria, and acellular pertussis (Tdap) booster; meningococcal conjugate vaccine (MenACWY); or human papillomavirus (HPV) vaccine. Separately for each vaccine, multivariable logistic regression identified adolescent and household correlates of concomitant versus single vaccination, stratified by adolescent sex. Vaccination took place in 2007-2012, data collection in 2008-2012, and data analysis in 2015. Among vaccinated adolescents, 51%-65% of girls and 25%-53% of boys received two vaccines concomitantly. Concomitant uptake of each vaccine increased over survey years (e.g., 2012 vs 2008: girls' Tdap booster, OR=1.88, 95% CI=1.56, 2.26; boys' Tdap booster, OR=2.62, 95% CI=2.16, 3.16), with the exception of HPV vaccination among boys. Additionally, concomitant vaccination was less common as adolescents got older and in the Northeast (all pvaccine, concomitant uptake was less common for girls whose mothers had higher versus lower education and for boys who lived in metropolitan versus non-metropolitan areas (all pvaccination persist, particularly for HPV vaccine. Future interventions targeting groups with low rates of concomitant vaccination could improve population-level coverage with recommended vaccines. Copyright © 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

  11. Humoral immune response of a pneumococcal conjugate vaccine: capsular polysaccharide serotype 14-Lysine modified PspA.

    Science.gov (United States)

    Santamaria, Raquel; Goulart, Cibelly; Perciani, Catia T; Barazzone, Giovana C; Carvalho, Rimenys; Gonçalves, Viviane M; Leite, Luciana C C; Tanizaki, Martha M

    2011-11-03

    Polysaccharide-protein conjugates are so far the current antigens used for pneumococcal vaccines for children under 2 years of age. In this study, pneumococcal surface protein A (PspA) was used as a carrier protein for pneumococcal capsular polysaccharide serotype 14 as an alternative to broaden the vaccine coverage. PspA was modified by reductive amination with formaldehyde in order to improve the specificity of the reaction between protein and polysaccharide, inhibiting polymerization and the gel formation reaction. In the synthesis process, the currently used activator, 1-[3-(dimethylamine)propyl]-3-ethylcarbodiimide hydrochloride (EDAC) was substituted for 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM). BALB/c mice were immunized with either the PS14-mPspA conjugate or the co-administered components in a three dose regimen and sera from the immunized animals were assayed for immunity induced against both antigens: PS14 and mPspA. Modification of more than 70% of lysine residues from PspA (mPspA) did not interfere in the immune response as evaluated by the anti-PspA titer and C3 complement deposition assay. Sera of mice immunized with conjugated PS14-mPspA showed similar IgG titers, avidity and isotype profile as compared to controls immunized with PspA or mPspA alone. The complement deposition was higher in the sera of mice immunized with the conjugate vaccine and the opsonophagocytic activity was similar for both sera. Conjugation improved the immune response against PS14. The anti PS14 IgG titer was higher in sera of mice immunized with the conjugate than with co-administered antigens and presented an increased avidity index, induction of a predominant IgG1 isotype and increased complement deposition on a bacteria with a surface serotype 14. These results strongly support the use of PspA as carrier in a conjugate vaccine where both components act as antigens. Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. Antibody Kinetics and Response to Routine Vaccinations in Infants Born to Women Who Received an Investigational Trivalent Group B Streptococcus Polysaccharide CRM197-Conjugate Vaccine During Pregnancy.

    Science.gov (United States)

    Madhi, Shabir A; Koen, Anthonet; Cutland, Clare L; Jose, Lisa; Govender, Niresha; Wittke, Frederick; Olugbosi, Morounfolu; Sobanjo-Ter Meulen, Ajoke; Baker, Sherryl; Dull, Peter M; Narasimhan, Vas; Slobod, Karen

    2017-11-13

    Maternal vaccination against group B Streptococcus (GBS) might provide protection against invasive GBS disease in infants. We investigated the kinetics of transplacentally transferred GBS serotype-specific capsular antibodies in the infants and their immune response to diphtheria toxoid and pneumococcal vaccination. This phase 1b/2, observer-blind, single-center study (NCT01193920) enrolled infants born to women previously randomized (1:1:1:1) to receive either GBS vaccine at dosages of 0.5, 2.5, or 5.0 μg of each of 3 CRM197-glycoconjugates (serotypes Ia, Ib, and III), or placebo. Infants received routine immunization: combination diphtheria vaccine (diphtheria-tetanus-acellular pertussis-inactivated poliovirus/Haemophilus influenzae type b vaccine; age 6/10/ 14 weeks) and 13-valent pneumococcal CRM197-conjugate vaccine (PCV13; age 6/14 weeks and 9 months). Antibody levels were assessed at birth, day (D) 43, and D91 for GBS serotypes; 1 month postdose 3 (D127) for diphtheria; and 1 month postprimary (D127) and postbooster (D301) doses for pneumococcal serotypes. Of 317 infants enrolled, 295 completed the study. In infants of GBS vaccine recipients, GBS serotype-specific antibody geometric mean concentrations were significantly higher than in the placebo group at all timepoints and predictably decreased to 41%-61% and 26%-76% of birth levels by D43 and D91, respectively. Across all groups, ≥95% of infants were seroprotected against diphtheria at D127 and ≥91% of infants had seroprotective antibody levels against each PCV13 pneumococcal serotype at D301. Maternal vaccination with an investigational CRM197-glycoconjugate GBS vaccine elicited higher GBS serotype-specific antibody levels in infants until 90 days of age, compared with a placebo group, and did not affect infant immune responses to diphtheria toxoid and pneumococcal vaccination. NCT01193920. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

  13. A reflection on invasive pneumococcal disease and pneumococcal conjugate vaccination coverage in children in Southern Europe (2009-2016).

    Science.gov (United States)

    Moreira, Marta; Castro, Olga; Palmieri, Melissa; Efklidou, Sofia; Castagna, Stefano; Hoet, Bernard

    2017-06-03

    Higher-valent pneumococcal conjugate vaccines (PCVs) were licensed from 2009 in Europe; similar worldwide clinical effectiveness was observed for PCVs in routine use. Despite a proven medical need, PCV vaccination in Southern Europe remained suboptimal until 2015/16. We searched PubMed for manuscripts published between 2009 and mid-2016. Included manuscripts had to contain data about invasive pneumococcal disease (IPD) incidence, or vaccination coverage with higher-valent PCVs. This review represents the first analysis of vaccination coverage and impact of higher-valent PCVs on overall IPD in Southern European countries (Portugal, Spain, Italy, Greece, Cyprus). Vaccination coverage in the Portuguese private market peaked around 2008 at 75% (children ≤ 2 years) but declined to 63% in 2012. In Madrid, coverage was 95% (2007-2012) but dropped to 67% (2013/14; children ≤ 2 years) after funding termination in May 2012. PCVs were recently introduced in the national immunisation program (NIP) of Portugal (2015) and Spain (2015/16). In Italy, coverage for the complete PCV schedule (children ≤ 2 years) was 88% in 2013, although highly variable between regions (45-99%). In Greece, in 2013, 82.3% had received 3 PCV doses by 12 months, while 62.3% received the fourth dose by 24 months. Overall IPD (net benefit: effect on vaccine types, vaccine-related types, and non-vaccine types) has decreased; in Greece, pneumococcal meningitis incidence remained stable. Continued IPD surveillance or national registers using ICD-10 codes of clinically suspected IPD are necessary, with timely publicly available reports and adequate national vaccination registers to assess trends in vaccination coverage, allowing evaluation of PCVs in NIPs.

  14. 76 FR 9358 - Notice of an Open Meeting of the Advisory Committee on Water Information (ACWI)

    Science.gov (United States)

    2011-02-17

    ... on Water Information (ACWI) AGENCY: United States Geological Survey, Department of the Interior... also of the utmost importance to everyone at the USGS to have your input into this process, and that... purpose of the ACWI is to provide a forum for water information users and professionals to advise the...

  15. Nasopharyngeal carriage of Streptococcus pneumoniae and other bacteria in the 7th year after implementation of the pneumococcal conjugate vaccine in the Netherlands

    NARCIS (Netherlands)

    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

    2016-01-01

    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.

  16. Clinical and bacteriological characteristics of invasive pneumococcal disease after pneumococcal 10-valent conjugate vaccine implementation in Salvador, Brazil

    Directory of Open Access Journals (Sweden)

    Carolina Regis Leite

    2016-01-01

    Full Text Available Invasive pneumococcal disease is a relevant public health problem in Brazil, especially among children and the elderly. In July/2010 a 10-valent pneumococcal conjugate vaccine was introduced to the immunization schedule of Brazilian children under two years of age. Between July/2010 and December/2013 we conducted a case-series study on invasive pneumococcal disease in Salvador, Brazil to describe the clinical and bacteriological profile of invasive pneumococcal disease cases during the post-implementation period. Eighty-two cases were eligible. Mean age was 31 years (interquartile range, 3–42; 17.1% and 30.5% were under 2 years and 5 years, respectively. Pneumococcal meningitis (n = 64, 78.1%, bacteraemic pneumococcal pneumonia (n = 12, 14.6% and bacteraemia (n = 6, 7.3% were the clinical syndromes identified. Thirty-three different serotypes were found. Of these, serotype 14 (n = 12, 14.6% was the most common, followed by 23F (n = 10, 12.2%, 12F (n = 8, 9.8%, 18 C (n = 5, 6.1% and 6B (n = 5, 6.1%. Investigations conducted in Salvador in the pre-vaccine period did not identify serotype 12F as one of the most prevalent serotypes. Increase of serotype 12F was observed in different regions of Brazil, in the post-vaccine period. Among children under two years of age, the target group for 10-valent pneumococcal conjugate vaccine, 11 (78.6% of the 14 isolated strains of Streptococcus pneumoniae belonged to vaccine serotypes; at least 50% of these children were not vaccinated. The relatively recent implementation of 10-valent pneumococcal conjugate vaccine in Brazil reinforces the need to maintain an active surveillance of invasive pneumococcal disease cases, considering the possible increase of invasive pneumococcal disease cases related to non-vaccine serotypes and the changes on the clinical presentation of the disease.

  17. Meningococcal groups C and Y and haemophilus B tetanus toxoid conjugate vaccine (HibMenCY-TT; MenHibrix(®)): a review.

    Science.gov (United States)

    Perry, Caroline M

    2013-05-01

    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

  18. Meningococcal Conjugate and Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccination Among HIV-infected Youth.

    Science.gov (United States)

    Setse, Rosanna W; Siberry, George K; Moss, William J; Wheeling, John; Bohannon, Beverly A; Dominguez, Kenneth L

    2016-05-01

    The meningococcal conjugate vaccine (MCV4) and the tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine (Tdap) were first recommended for adolescents in the US in 2005. The goal of our study was to determine MCV4 and Tdap vaccines coverage among perinatally and behaviorally HIV-infected adolescents in 2006 and to compare coverage estimates in our study population to similarly aged healthy youth in 2006. Longitudinal Epidemiologic Study to Gain Insight into HIV/AIDS in Children and Youth (LEGACY) is a retrospective cohort study of HIV-infected youth in 22 HIV specialty clinics across the US. Among LEGACY participants ≥11 years of age in 2006, we conducted a cross-sectional analysis to determine MCV4, Tdap and MCV4/Tdap vaccine coverage. We compared vaccine coverage among our study population to coverage among similarly aged youth in the 2006 National Immunization Survey for Teens (NIS-Teen Survey). Multivariable mixed effects logistic regression modeling was used to examine associations between MCV4/Tdap vaccination and mode of HIV transmission. MCV4 and Tdap coverage rates among 326 eligible participants were 31.6% and 28.8%, respectively. Among adolescents 13-17 years of age, MCV4 and Tdap coverage was significantly higher among HIV-infected youth than among youth in the 2006 NIS-Teen Survey (P 400 copies/mL were significantly less likely to have received MCV4/Tdap vaccination (P < 0.05). MCV4 and Tdap coverage among HIV-infected youth was suboptimal but higher than for healthy adolescents in the 2006 NIS-Teen Survey. Perinatal HIV infection was associated with increased likelihood of vaccination. Specific measures are needed to improve vaccine coverage among adolescents in the US.

  19. Estimated effect of pneumococcal conjugate vaccination on invasive pneumococcal disease and associated mortality, Denmark 2000-2005

    DEFF Research Database (Denmark)

    Harboe, Z.B.; Valentiner-Branth, P.; Benfield, T.L.

    2008-01-01

    In order to provide an estimation of the direct and indirect benefits of pneumococcal vaccination with three protein-conjugate pneumococcal vaccines (PCV) we described the epidemiology and mortality from invasive pneumococcal disease (IPD) in Denmark between 2000 and 2005. Approximately 1080 cases......% to 91% depending on the PCV used. The mean mortality proportion after IPD was 18%, with approximately 190 deaths annually. One to two deaths among children younger than 5 years and approximately 50 deaths related to IPD caused by vaccine serotypes among older age groups could be prevented annually...... were registered annually during the period. The overall incidence of IPD increased significantly, from 15.4 cases per 100,000 population in 2000 to 20.7 cases per 100,000 in 2005 (pcases. The serotype coverage in children under 5 years varied from 64...

  20. Estimated effect of pneumococcal conjugate vaccination on invasive pneumococcal disease and associated mortality, Denmark 2000-2005

    DEFF Research Database (Denmark)

    Harboe, Z.B.; Valentiner-Branth, P.; Benfield, T.L.

    2008-01-01

    % to 91% depending on the PCV used. The mean mortality proportion after IPD was 18%, with approximately 190 deaths annually. One to two deaths among children younger than 5 years and approximately 50 deaths related to IPD caused by vaccine serotypes among older age groups could be prevented annually......In order to provide an estimation of the direct and indirect benefits of pneumococcal vaccination with three protein-conjugate pneumococcal vaccines (PCV) we described the epidemiology and mortality from invasive pneumococcal disease (IPD) in Denmark between 2000 and 2005. Approximately 1080 cases...... were registered annually during the period. The overall incidence of IPD increased significantly, from 15.4 cases per 100,000 population in 2000 to 20.7 cases per 100,000 in 2005 (pchildren under 5 years varied from 64...

  1. Monitoring the introduction of pneumococcal conjugate vaccines into West Africa: design and implementation of a population-based surveillance system.

    Directory of Open Access Journals (Sweden)

    Grant A Mackenzie

    2012-01-01

    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.

  2. Pneumococcal pneumonia prevention among adults: is the herd effect of pneumococcal conjugate vaccination in children as good a way as the active immunization of the elderly?

    Science.gov (United States)

    Prato, Rosa; Fortunato, Francesca; Martinelli, Domenico

    2016-01-01

    The indirect protection of adults as a result of pneumococcal conjugate vaccination of infants has been discussed from different epidemiological points of view. In some countries, including Italy, even after pediatric vaccination, vaccine serotypes are still responsible for most pneumonia and invasive diseases in the elderly. Although the Community-Acquired Pneumonia Immunization Trial in Adults (CAPITA) produced encouraging results, it has not showed the efficacy of the 13-valent conjugate vaccine in preventing pneumococcal community-acquired pneumonia regardless of the number of episodes and serotype. Addressing these points by monitoring the direct impact of adult vaccination in real life distinguished from the effects of herd immunity will assist public health decision-making on the most effective adult pneumococcal vaccination strategies.

  3. Evaluation in mice of a conjugate vaccine for cholera made from Vibrio cholerae O1 (Ogawa O-specific polysaccharide.

    Directory of Open Access Journals (Sweden)

    Mohammad Murshid Alam

    2014-02-01

    Full Text Available Protective immunity against cholera is serogroup specific. Serogroup specificity in Vibrio cholerae is determined by the O-specific polysaccharide (OSP of lipopolysaccharide (LPS. Generally, polysaccharides are poorly immunogenic, especially in young children.Here we report the evaluation in mice of a conjugate vaccine for cholera (OSP:TThc made from V. cholerae O1 Ogawa O-Specific Polysaccharide-core (OSP and recombinant tetanus toxoid heavy chain fragment (TThc. We immunized mice intramuscularly on days 0, 21, and 42 with OSP:TThc or OSP only, with or without dmLT, a non-toxigenic immunoadjuvant derived from heat labile toxin of Escherichia coli.We detected significant serum IgG antibody responses targeting OSP following a single immunization in mice receiving OSP:TThc with or without adjuvant. Anti-LPS IgG responses were detected following a second immunization in these cohorts. No anti-OSP or anti-LPS IgG responses were detected at any time in animals receiving un-conjugated OSP with or without immunoadjuvant, and in animals receiving immunoadjuvant alone. Responses were highest following immunization with adjuvant. Serum anti-OSP IgM responses were detected in mice receiving OSP:TThc with or without immunoadjuvant, and in mice receiving unconjugated OSP. Serum anti-LPS IgM and vibriocidal responses were detected in all vaccine cohorts except in mice receiving immunoadjuvant alone. No significant IgA anti-OSP or anti-LPS responses developed in any group. Administration of OSP:TThc and adjuvant also induced memory B cell responses targeting OSP and resulted in 95% protective efficacy in a mouse lethality cholera challenge model.We describe a protectively immunogenic cholera conjugate in mice. Development of a cholera conjugate vaccine could assist in inducing long-term protective immunity, especially in young children who respond poorly to polysaccharide antigens.

  4. Optimising assessments of the epidemiological impact in the Netherlands of paediatric immunisation with 13-valent pneumococcal conjugate vaccine using dynamic transmission modelling

    OpenAIRE

    De Cao, Elisabetta; Melegaro, Alessia; Klok, Rogier; Postma, Maarten

    2014-01-01

    This work is the first attempt to quantify the overall effects of a 13-valent pneumococcal conjugate vaccine (PCV13) vaccination programme in the Dutch population taking into account all the direct and indirect effects of the vaccine on invasive pneumococcal disease. Using available Dutch data, a dynamic transmission model for the spread of pneumococci and potential subsequent invasive pneumococcal disease has been adapted to the Dutch setting. Overall, invasive pneumococcal disease cases in ...

  5. Persistence of Meningococcal Antibodies and Response to a Third Dose After a Two-dose Vaccination Series with Investigational MenABCWY Vaccine Formulations in Adolescents.

    Science.gov (United States)

    Saez-Llorens, Xavier; Aguilera Vaca, Diana Catalina; Abarca, Katia; Maho, Emmanuelle; Han, Linda; Smolenov, Igor; Dull, Peter

    2015-10-01

    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.

  6. Long-term impact of 10-valent pneumococcal conjugate vaccination on invasive pneumococcal disease among children in Finland.

    Science.gov (United States)

    Rinta-Kokko, Hanna; Palmu, Arto A; Auranen, Kari; Nuorti, J Pekka; Toropainen, Maija; Siira, Lotta; Virtanen, Mikko J; Nohynek, Hanna; Jokinen, Jukka

    2018-04-05

    The ten-valent pneumococcal conjugate vaccine (PCV10) was introduced into the Finnish National Vaccination Programme (NVP) in September 2010. The impact of PCV10 vaccination against invasive pneumococcal disease (IPD) in vaccine-eligible children has been high. We evaluated the long-term impact of PCV10 vaccination against IPD in vaccine-eligible and older, unvaccinated children six years after PCV10 introduction with a special focus on cross-protection against PCV10-related serotypes (serotypes in the same serogroups as the PCV10 types). We used data on IPD from the national, population-based surveillance. A target cohort of vaccine-eligible children (born June 2010 or later) was followed from 3 months of age until the end of 2016. For the indirect effect, another cohort of older PCV10-ineligible children was followed from 2012 through 2016. IPD rates were compared with those of season- and age-matched reference cohorts before NVP introduction. Among vaccine-eligible children, the incidence of all IPD decreased by 79% (95% CI 74-83%). There was a statistically significant reduction in the incidence of 6A IPD, but for 19A, the reduction was non-significant and the incidence of 19A increased towards the end of the study period in the older vaccine-eligible children. The increase in non-PCV10 related serotypes was non-significant. In the unvaccinated older children, the incidence of all IPD decreased by 33% (95% CI 8-52%) compared to the reference cohort, and there was no impact on serotype 6A or 19A IPD. Overall, the impact of PCV10 vaccination on IPD was high in vaccine-eligible children, with a major reduction in vaccine-type disease, and without notable replacement by other serotype groups. Our data suggest that PCV10 results in long-lasting direct cross-protection against 6A IPD. For 19A, no net reduction was observed six years after NVP introduction in the vaccine-eligible cohort. The indirect impact on IPD in unvaccinated children sustained. Copyright

  7. Efficacy of an influenza hemagglutinin-diphtheria toxoid conjugate vaccine in elderly nursing home subjects during an influenza outbreak.

    Science.gov (United States)

    Gravenstein, S; Drinka, P; Duthie, E H; Miller, B A; Brown, C S; Hensley, M; Circo, R; Langer, E; Ershler, W B

    1994-03-01

    To compare the efficacy of an influenza hemagglutinin-diphtheria toxoid conjugate vaccine with the commercially available influenza hemagglutinin-subunit vaccine in preventing influenza in older adults living in a nursing home. A prospective, randomized, double-blind vaccine trial with 5 months of follow-up after vaccination. Fourteen Wisconsin nursing homes. Nursing home residents at least 65 years old who were able to give informed consent and were free of malignancy and not receiving immunosuppressive therapy. Participants received, by intramuscular injection, 0.5 mL of a trivalent influenza vaccine containing 15 micrograms each of A/Leningrad/360/86 (H3N2), A/Taiwan/1/86 (H1N1), and B/Ann Arbor/1/86 (HA) or 0.5 mL of an influenza vaccine containing the same antigens conjugated to diphtheria toxoid (HA-D). Blood was obtained pre- and 1 month post-vaccination to assess for any vaccine-induced antibody titer change. Clinical surveillance for respiratory illness was performed twice weekly for 5 months. A record was kept of all signs and symptoms of new respiratory illness, and a viral culture and acute and convalescent sera were obtained. 204 participants received HA and 204 received HA-D. Both groups had similar baseline antibody levels to all influenza antigens. HA-D recipients seroconverted more frequently based on serum neutralizing activity (P < 0.05), had a greater increase in geometric mean titer (GMT), and sustained the increase in antibody titer longer than HA recipients. Vaccine hemagglutinin recall was greater in a subset of HA-D recipients as measured by lymphocyte proliferative assays (P < 0.05). During an outbreak of influenza A (H3N2 A/Shanghai/11/87-like and A/Victoria/7/87-like), fewer HA-D (29/195) than HA (43/204) recipients had laboratory-confirmed infection (P = 0.053), and, of these, fewer HA-D-treated subjects had lower respiratory tract involvement (5/29 HA-D and 17/43 HA) (P = 0.022). HA-D was more immunogenic in institutionalized elderly

  8. Uptake of meningococcal conjugate vaccine among adolescents in large managed care organizations, United States, 2005: Demand, supply and seasonality

    Directory of Open Access Journals (Sweden)

    Wortley Pascale M

    2009-11-01

    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.

  9. Influence of prevaccination immunity on the human B-lymphocyte response to a Haemophilus influenzae type b conjugate vaccine

    DEFF Research Database (Denmark)

    Barington, T; Kristensen, K; Henrichsen, J

    1991-01-01

    of Haemophilus influenzae type b capsular polysaccharide (PRP) and diphtheria toxoid (DT), and the response was related to the prevaccination levels of PRP and DT antibodies. Positive correlations were found between increases in plasma PRP (median, 32.0 micrograms/ml) and DT (1.14 IU/ml) antibodies and numbers......The purpose of this study was to investigate whether preexisting immunity to components of a polysaccharide-protein conjugate influences the B-lymphocyte response to vaccination with the conjugate. Thirty-two healthy adults were vaccinated once or twice with a conjugate (PRP-D) consisting...... of circulating PRP and DT antibody-secreting cells (AbSC) (postvaccination days 6 to 9). The B-cell responses (antibody response and AbSC) to both PRP and DT correlated positively with prevaccination levels of anti-DT. DT AbSC appeared earlier (peak, day 7) than PRP AbSC (peak, day 8). Individuals whose PRP Ab...

  10. Pneumococcal bacteraemia in Belgium (1994 2004): the pre-conjugate vaccine era.

    Science.gov (United States)

    Flamaing, Johan; Verhaegen, Jan; Vandeven, Jos; Verbiest, Nadine; Peetermans, Willy E

    2008-01-01

    To analyse the evolution of antibiotic resistance and serotype distribution in pneumococcal bacteraemia before the introduction of the 7-valent pneumococcal conjugate vaccine (7PCV). Serotyping and susceptibility testing for penicillin and erythromycin were performed on 11 163 blood isolates of Streptococcus pneumoniae collected between 1994 and 2004. Penicillin resistance rose from 4.7% in 1994 to 15.2% (P = 0.001) in 2000 and decreased thereafter to 9.7% (P = 0.001) in 2004. Erythromycin resistance rose from 20.4% in 1994 to 34.4% (P = 0.001 in 2001) and stabilized thereafter. Paediatric serogroups/serotypes (SGTs) (SGTs 6, 9, 14, 19 and 23; 47.4% of bacteraemic isolates), characterized by decreasing penicillin and stable erythromycin resistance, decreased by the end of the study period. Non-paediatric SGTs (SGTs 1, 5 and 7; 20.5% of bacteraemic isolates), characterized by temporal fluctuations, the absence of penicillin resistance and rising erythromycin resistance, increased significantly by the end of the study period. The age group 5-59 years was most affected by these changes. Compared with the age group or=60 years has a relative risk of 7.6 (CI: 4-11.6; P = 0.001) of having a pneumococcal bacteraemia with SGT 3. The overall coverage rate of bacteraemic SGTs offered by the 7PCV is 81.9% in the or=60 years age group is 78.7% and 95%, respectively. Although the 7PCV was not used in Belgium during the study period, the overall prevalence in paediatric SGTs decreased significantly. This may be linked to secular trends in SGTs not included in the 7PCV and/or herd effects at the international level. Overall penicillin resistance decreased as well and this may be due to a shift towards susceptible serotypes and/or a decrease in antibiotic use in our country. Antibiotic resistance and trends in SGT distribution will need further surveillance in order to assess 7PCV effects on pneumococcal epidemiology, to adapt future vaccine formulations and to target the

  11. Process development of a New Haemophilus influenzae type b conjugate vaccine and the use of mathematical modeling to identify process optimization possibilities.

    Science.gov (United States)

    Hamidi, Ahd; Kreeftenberg, Hans; V D Pol, Leo; Ghimire, Saroj; V D Wielen, Luuk A M; Ottens, Marcel

    2016-05-01

    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.

  12. T-cell-mediated immune response to pneumococcal conjugate vaccine (PCV-13) and tetanus toxoid vaccine in patients with moderate-to-severe psoriasis during tofacitinib treatment.

    Science.gov (United States)

    Winthrop, Kevin L; Korman, Neil; Abramovits, William; Rottinghaus, Scott T; Tan, Huaming; Gardner, Annie; Mukwaya, Geoffrey; Kaur, Mandeep; Valdez, Hernan

    2018-03-01

    Psoriasis is often treated with immunomodulatory therapies that can affect the immune response to common antigens. Tofacitinib is an oral Janus kinase inhibitor. To characterize the effect of long-term exposure to tofacitinib 10 mg twice daily on T-cell function in psoriasis patients. Patients completing at least 3 months' continuous treatment with tofacitinib 10 mg twice daily were vaccinated with T-cell-dependent vaccines (monovalent tetanus toxoid and 13-valent pneumococcal conjugate [PCV-13]). Patients were assessed at baseline (before vaccination) and then again 4 weeks after vaccination. For PCV-13, we evaluated serotype-specific, opsonophagocytic antibody responses, and for tetanus toxoid, we evaluated humoral responses. Among 60 patients who completed the study, the geometric mean fold rise from baseline for the 13 PCV serotypes at 4 weeks postvaccination varied from 8.3 (serotype 3) to 101.9 (serotype 6A). Similar results were observed for patients with and without lymphopenia at baseline. For tetanus toxoid, 51 (88%) patients had ≥2-fold and 35 (60%) patients had ≥4-fold rise in antibody concentration. There was no placebo control. Most psoriasis patients who receive tofacitinib can mount satisfactory T-cell-dependent responses to PCV-13 and tetanus vaccines. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  13. Nationwide Trends in Bacterial Meningitis before the Introduction of 13-Valent Pneumococcal Conjugate Vaccine-Burkina Faso, 2011-2013.

    Science.gov (United States)

    Kambiré, Dinanibè; Soeters, Heidi M; Ouédraogo-Traoré, Rasmata; Medah, Isaïe; Sangare, Lassana; Yaméogo, Issaka; Sawadogo, Guetawendé; Ouédraogo, Abdoul-Salam; Hema-Ouangraoua, Soumeya; McGee, Lesley; Srinivasan, Velusamy; Aké, Flavien; Congo-Ouédraogo, Malika; Sanou, Soufian; Ba, Absatou Ky; Novak, Ryan T; Van Beneden, Chris

    2016-01-01

    Following introduction of Haemophilus influenzae type b vaccine in 2006 and serogroup A meningococcal conjugate vaccine in 2010, Streptococcus pneumoniae (Sp) became the leading cause of bacterial meningitis in Burkina Faso. We describe bacterial meningitis epidemiology, focusing on pneumococcal meningitis, before 13-valent pneumococcal conjugate vaccine (PCV13) introduction in the pediatric routine immunization program in October 2013. Nationwide population-based meningitis surveillance collects case-level demographic and clinical information and cerebrospinal fluid (CSF) laboratory results. Sp infections are confirmed by culture, real-time polymerase chain reaction (rt-PCR), or latex agglutination, and CSF serotyped using real-time and conventional PCR. We calculated incidence rates in cases per 100,000 persons, adjusting for age and proportion of cases with CSF tested at national reference laboratories, and case fatality ratios (CFR). During 2011-2013, 1,528 pneumococcal meningitis cases were reported. Average annual adjusted incidence rates were 26.9 (meningitis occurred among children aged <1 year. The majority of cases were due to PCV13-associated serotypes; introduction of PCV13 should substantially decrease this burden.

  14. MF59 oil-in-water emulsion in combination with a synthetic TLR4 agonist (E6020) is a potent adjuvant for a combination Meningococcus vaccine.

    Science.gov (United States)

    Singh, Manmohan; Kazzaz, Jina; Ugozzoli, Mildred; Baudner, Barbara; Pizza, Mariagrazia; Giuliani, Marzia; Hawkins, Lynn D; Otten, Gillis; O'Hagan, Derek T

    2012-04-01

    The inclusion of a potent TLR4 immune potentiator to a recombinant antigen vaccine formulation enhances both the magnitude and the breadth of the engendered immune response. One such immune potentiator (TLR4 agonist E6020) was evaluated with recombinant Men B antigens delivered in MF59 sub-micron adjuvant emulsion. The ability of this formulation to enhance serum antibody and bactercidal titers was investigated. The co-delivery of E6020 within MF59 enhanced both the serum and bactericidal titers for Men B antigens and for Men B antigens combined with Men ACWY-CRM conjugate vaccine. The delivery of TLR4 agonist within MF59 emulsion oil droplets leads to a more potent response in comparison to the TLR4 when admixed with MF59 emulsion.

  15. Enhanced immunogenicity of a tricomponent mannan tetanus toxoid conjugate vaccine targeted to dendritic cells via Dectin-1 by incorporating β-glucan.

    Science.gov (United States)

    Lipinski, Tomasz; Fitieh, Amira; St Pierre, Joëlle; Ostergaard, Hanne L; Bundle, David R; Touret, Nicolas

    2013-04-15

    In a previous attempt to generate a protective vaccine against Candida albicans, a β-mannan tetanus toxoid conjugate showed poor immunogenicity in mice. To improve the specific activation toward the fungal pathogen, we aimed to target Dectin-1, a pattern-recognition receptor expressed on monocytes, macrophages, and dendritic cells. Laminarin, a β-glucan ligand of Dectin-1, was incorporated into the original β-mannan tetanus toxoid conjugate providing a tricomponent conjugate vaccine. A macrophage cell line expressing Dectin-1 was employed to show binding and activation of Dectin-1 signal transduction pathway by the β-glucan-containing vaccine. Ligand binding to Dectin-1 resulted in the following: 1) activation of Src family kinases and Syk revealed by their recruitment and phosphorylation in the vicinity of bound conjugate and 2) translocation of NF-κB to the nucleus. Treatment of immature bone marrow-derived dendritic cells (BMDCs) with tricomponent or control vaccine confirmed that the β-glucan-containing vaccine exerted its enhanced activity by virtue of dendritic cell targeting and uptake. Immature primary cells stimulated by the tricomponent vaccine, but not the β-mannan tetanus toxoid vaccine, showed activation of BMDCs. Moreover, treated BMDCs secreted increased levels of several cytokines, including TGF-β and IL-6, which are known activators of Th17 cells. Immunization of mice with the novel type of vaccine resulted in improved immune response manifested by high titers of Ab recognizing C. albicans β-mannan Ag. Vaccine containing laminarin also affected distribution of IgG subclasses, showing that vaccine targeting to Dectin-1 receptor can benefit from augmentation and immunomodulation of the immune response.

  16. Pneumococcal Vaccination Among Medicare Beneficiaries Occurring After the Advisory Committee on Immunization Practices Recommendation for Routine Use Of 13-Valent Pneumococcal Conjugate Vaccine and 23-Valent Pneumococcal Polysaccharide Vaccine for Adults Aged ≥65 Years.

    Science.gov (United States)

    Black, Carla L; Williams, Walter W; Warnock, Rob; Pilishvili, Tamara; Kim, David; Kelman, Jeffrey A

    2017-07-14

    On September 19, 2014, CDC published the Advisory Committee on Immunization Practices (ACIP) recommendation for the routine use of 13-valent pneumococcal conjugate vaccine (PCV13) among adults aged ≥65 years, to be used in series with 23-valent pneumococcal polysaccharide vaccine (PPSV23) (1). This replaced the previous recommendation that adults aged ≥65 years should be vaccinated with a single dose of PPSV23. As a proxy for estimating PCV13 and PPSV23 vaccination coverage among adults aged ≥65 years before and after implementation of these revised recommendations, CDC analyzed claims for vaccination submitted for reimbursement to the Centers for Medicare & Medicaid Services (CMS). Claims from any time during a beneficiary's enrollment in Medicare Parts A (hospital insurance) and B (medical insurance) since reaching age 65 years were assessed among beneficiaries continuously enrolled in Medicare Parts A and B during annual periods from September 19, 2009, through September 18, 2016. By September 18, 2016, 43.2% of Medicare beneficiaries aged ≥65 years had claims for at least 1 dose of PPSV23 (regardless of PCV13 status), 31.5% had claims for at least 1 dose of PCV13 (regardless of PPSV23 status), and 18.3% had claims for at least 1 dose each of PCV13 and PPSV23. Claims for either type of pneumococcal vaccine were highest among beneficiaries who were older, white, or with chronic and immunocompromising medical conditions than among healthy adults. Implementation of the National Vaccine Advisory Committee's standards for adult immunization practice to assess vaccination status at every patient encounter, recommend needed vaccines, and administer vaccination or refer to a vaccinating provider might help increase pneumococcal vaccination coverage and reduce the risk for pneumonia and invasive pneumococcal disease among older adults (2).

  17. Patterns of binding of aluminum-containing adjuvants to Haemophilus influenzae type b and meningococcal group C conjugate vaccines and components.

    Science.gov (United States)

    Otto, Robert B D; Burkin, Karena; Amir, Saba Erum; Crane, Dennis T; Bolgiano, Barbara

    2015-09-01

    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.

  18. Patterns of binding of aluminum-containing adjuvants to Haemophilus influenzae type b and meningococcal group C conjugate vaccines and components

    Science.gov (United States)

    Otto, Robert B.D.; Burkin, Karena; Amir, Saba Erum; Crane, Dennis T.; Bolgiano, Barbara

    2015-01-01

    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

  19. Challenges and Opportunities While Developing a Group A Meningococcal Conjugate Vaccine Within a Product Development Partnership: A Manufacturer's Perspective From the Serum Institute of India

    Science.gov (United States)

    Kulkarni, Prasad S.; Socquet, Muriel; Jadhav, Suresh S.; Kapre, Subhash V.; LaForce, F. Marc; Poonawalla, Cyrus S.

    2015-01-01

    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

  20. Early impact of 13-valent pneumococcal conjugate vaccine on pneumococcal meningitis-Burkina Faso, 2014-2015.

    Science.gov (United States)

    Kambiré, Dinanibè; Soeters, Heidi M; Ouédraogo-Traoré, Rasmata; Medah, Isaïe; Sangaré, Lassana; Yaméogo, Issaka; Sawadogo, Guetawendé; Ouédraogo, Abdoul-Salam; Ouangraoua, Soumeya; McGee, Lesley; Srinivasan, Velusamy; Aké, Flavien; Congo-Ouédraogo, Malika; Ky Ba, Absatou; Whitney, Cynthia G; Novak, Ryan T; Van Beneden, Chris

    2018-03-01

    We evaluate early impact of 13-valent pneumococcal conjugate vaccine (PCV13) on pneumococcal meningitis in Burkina Faso. Nationwide surveillance gathered demographic/clinical information and cerebrospinal fluid (CSF) results for meningitis cases. Pneumococcal cases were confirmed by culture, polymerase chain reaction (PCR), or latex agglutination, and strains serotyped using PCR. We compared incidence (cases per 100,000) in the early post-PCV13 period (2014 and 2015) to average pre-PCV13 incidence (2011-2013). In 2015, age-specific pneumococcal meningitis incidences were 8.7 (disease in older children and adults requires continued monitoring. Published by Elsevier Ltd.

  1. Cost-effectiveness of alternate strategies for childhood immunization against meningococcal disease with monovalent and quadrivalent conjugate vaccines in Canada.

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    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.

  2. Cost-effectiveness of alternate strategies for childhood immunization against meningococcal disease with monovalent and quadrivalent conjugate vaccines in Canada.

    Science.gov (United States)

    Delea, Thomas E; Weycker, Derek; Atwood, Mark; Neame, Dion; Alvarez, Fabián P; Forget, Evelyn; Langley, Joanne M; Chit, Ayman

    2017-01-01

    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.

  3. A cost-effectiveness analysis of a 10-valent pneumococcal conjugate vaccine in children in six Latin American countries

    Science.gov (United States)

    2013-01-01

    Background A recently developed 10-valent pneumococcal non-typeable H influenzae protein D-conjugate vaccine (PHiD-CV) is expected to afford protection against more than two thirds of isolates causing IPD in children in Latin America, and also against acute otitis media caused by both Spn and NTHi. The objective of this study is to assess the cost-effectiveness of PHiD-CV in comparison to non-vaccination in children under 10 years of age in Argentina, Brazil, Chile, Colombia, Mexico and Peru. Methods We used a static, deterministic, compartmental simulation model. The dosing regimen considered included three vaccine doses (at 2 months, 4 months and 6 months) and a booster dose (at 13 months) (3 + 1 schedule). Model outcomes included number of cases prevented, deaths averted, quality-adjusted life-years (QALYs) gained and costs. Discount for costs and benefits of long term sequelae was done at 3.5%, and currency reported in 2008-2009 U$S varying between countries. Results The largest effect in case prevention was observed in pneumococcal meningitis (from 27% in Peru to 47% in Colombia), neurologic sequelae after meningitis (from 38% in Peru to 65% in Brazil) and bacteremia (from 42% in Argentina to 49% in Colombia). The proportion of predicted deaths averted annually ranged from 18% in Peru to 33% in Brazil. Overall, the health benefits achieved with PHiD-CV vaccination resulted in a lower QALY loss (from 15% lower in Peru to 26% in Brazil). At a cost of USD 20 per vaccine dose, vaccination was cost-effective in all countries, from being cost saving in Chile to a maximum Incremental Cost-effectiveness Ratio of 7,088 US$ Dollars per QALY gained. Results were robust in the sensitivity analysis, and scenarios with indirect costs affected results more than those with herd immunity. Conclusions The incorporation of the 10-valent pneumococcal conjugate vaccine into routine infant immunization programs in Latin American countries could be a cost-effective strategy

  4. Pneumococcal antibody concentrations of subjects in communities fully or partially vaccinated with a seven-valent pneumococcal conjugate vaccine.

    Directory of Open Access Journals (Sweden)

    Martin O C Ota

    Full Text Available A recent trial with PCV-7 in a rural Gambian community showed reduced vaccine-type pneumococcal carriage in fully vaccinated compared with control communities. We measured pneumococcal polysaccharide antibody concentrations in this trial to understand further the mechanisms underlying the observed changes.A single-blind, cluster-randomized (by village trial was conducted in 21 Gambian villages. In 11 villages, all residents received PCV-7 (Vaccine group; in 10 control villages only children 5.0 µg/mL for all but serotype 9V of the PCV-7 serotypes in the older group, but not in the younger age group.Higher antibodies in vaccinated communities provide an explanation for the lower pneumococcal carriage rates in fully vaccinated compared to control communities.Controlled-Trials.com ISRCTN51695599 51695599.

  5. The early kinetics of circulating pneumococcal-specific memory B cells following pneumococcal conjugate and plain polysaccharide vaccines in the elderly.

    Science.gov (United States)

    Baxendale, Helen E; Keating, Sheila M; Johnson, Marina; Southern, Jo; Miller, Elizabeth; Goldblatt, David

    2010-07-05

    In young children, polyvalent pneumococcal polysaccharide conjugate vaccines (PCVs) have been shown to offer advantage over plain polysaccharide vaccines (PPVs) in both immunogenicity and priming for memory responses. In the elderly, the potential benefit of conjugate vaccines is unclear. Here, we explore the early kinetics of serum antibody and circulating plasma and memory B cell responses to pneumococcal capsular polysaccharide (PPS) in older adults (n=37) immunised a PPV vaccine, Pneumovax or a PCV: Prevenar. All individuals had serum evidence of pre-existing serotype-specific immunity. Following immunisation, a day 7 rise in circulating PPS-specific plasma and memory antibody secreting cells (AbSCs) was detected in both vaccine groups and this was sustained to day 28 in some PCV recipients. There was no difference between vaccine groups in serum antibody responses or the kinetics of the early PBMC-derived B cell responses. Although our sample cohort was small, these data are different from profiles in younger individuals at early time points post-immunisation and suggest that pneumococcal conjugate vaccines may not quantitatively enhance the generation of memory responses in the elderly. Copyright 2010 Elsevier Ltd. All rights reserved.

  6. Impact of 10-valent pneumococcal conjugate vaccine on pneumococcal meningitis in children up to two years of age in Brazil

    Directory of Open Access Journals (Sweden)

    Indianara Maria Grando

    2015-02-01

    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.

  7. Haemophilus influenzae type b-Neisseria meningitidis serogroups C and Y tetanus toxoid conjugate vaccine for infants and toddlers.

    Science.gov (United States)

    Bryant, Kristina A; Marshall, Gary S

    2011-07-01

    The highest rates of invasive meningococcal disease occur in children under 2 years of age, yet as of early 2011 no vaccine was licensed for the youngest infants. However, a novel vaccine consisting of capsular polysaccharides from Haemophilus influenzae type b (Hib) and Neisseria meningitidis serogroups C and Y conjugated to tetanus toxoid (HibMenCY-TT; MenHibrix, GlaxoSmithKline) is in the late stages of development. In clinical trials involving more than 7800 children, HibMenCY-TT was shown to be safe and immunogenic when administered at 2, 4, 6 and 12-15 months of age. Anti-polyribosylribitol phosphate antibody responses were noninferior to those elicited by licensed monovalent Hib vaccines, and most vaccinees developed bactericidal antibodies against N. meningitidis serogroups C and Y. The majority of subjects retained antibody responses as far as 3 years after vaccination. If licensed, HibMenCY-TT not only represents an incremental option for protection against invasive Hib, but also has the potential to prevent invasive meningococcal disease without increasing the number of injections.

  8. Phenotypic and genotypic characterization of meningococcal carriage and disease isolates in Burkina Faso after mass vaccination with a serogroup a conjugate vaccine.

    Science.gov (United States)

    Kristiansen, Paul A; Ba, Absatou Ky; Sanou, Idrissa; Ouédraogo, Abdoul-Salam; Ouédraogo, Rasmata; Sangaré, Lassana; Diomandé, Fabien; Kandolo, Denis; Thomas, Jennifer Dolan; Clark, Thomas A; Laforce, Marc; Caugant, Dominique A

    2013-08-02

    The conjugate vaccine against serogroup A Neisseria meningitidis (NmA), MenAfriVac, was first introduced in mass vaccination campaigns of the 1-29-year-olds in Burkina Faso in 2010. The aim of this study was to genetically characterize meningococcal isolates circulating in Burkina Faso before and up to 13 months after MenAfriVac mass vaccination. A total of 1,659 meningococcal carriage isolates were collected in a repeated cross-sectional carriage study of the 1-29-year-olds in three districts of Burkina Faso in 2010 and 2011, before and up to 13 months after mass vaccination. Forty-two invasive isolates were collected through the national surveillance in Burkina Faso in the same period. All the invasive isolates and 817 carriage isolates were characterized by serogroup, multilocus sequence typing and porA-fetA sequencing. Seven serogroup A isolates were identified, six in 2010, before vaccination (4 from carriers and 2 from patients), and one in 2011 from an unvaccinated patient; all were assigned to sequence type (ST)-2859 of the ST-5 clonal complex. No NmA carriage isolate and no ST-2859 isolate with another capsule were identified after vaccination. Serogroup X carriage and disease prevalence increased before vaccine introduction, due to the expansion of ST-181, which comprised 48.5% of all the characterized carriage isolates. The hypervirulent serogroup W ST-11 clone that was responsible for most of meningococcal disease in 2011 and 2012 was not observed in 2010; it appeared during the epidemic season of 2011, when it represented 40.6% of the serogroup W carriage isolates. Successive clonal waves of ST-181 and ST-11 may explain the changing epidemiology in Burkina Faso after the virtual disappearance of NmA disease and carriage. No ST-2859 strain of any serogroup was found after vaccination, suggesting that capsule switching of ST-2859 did not occur, at least not during the first 13 months after vaccination.

  9. Introducción de la vacuna conjugada contra Hib en Chile y Uruguay Introducing Hib conjugate vaccine in Chile and Uruguay

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    Mauricio Landaverde

    1999-03-01

    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.

  10. Synthesis and biological evaluation of a novel MUC1 glycopeptide conjugate vaccine candidate comprising a 4’-deoxy-4’-fluoro-Thomsen–Friedenreich epitope

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    Manuel Johannes

    2015-01-01

    Full Text Available The development of selective anticancer vaccines that provide enhanced protection against tumor recurrence and metastasis has been the subject of intense research in the scientific community. The tumor-associated glycoprotein MUC1 represents a well-established target for cancer immunotherapy and has been used for the construction of various synthetic vaccine candidates. However, many of these vaccine prototypes suffer from an inherent low immunogenicity and are susceptible to rapid in vivo degradation. To overcome these drawbacks, novel fluorinated MUC1 glycopeptide-BSA/TTox conjugate vaccines have been prepared. Immunization of mice with the 4’F-TF-MUC1-TTox conjugate resulted in strong immune responses overriding the natural tolerance against MUC1 and producing selective IgG antibodies that are cross-reactive with native MUC1 epitopes on MCF-7 human cancer cells.

  11. Immunogenicity and safety of investigational vaccine formulations against meningococcal serogroups A, B, C, W, and Y in healthy adolescents.

    Science.gov (United States)

    Saez-Llorens, Xavier; Aguilera Vaca, Diana Catalina; Abarca, Katia; Maho, Emmanuelle; Graña, Maria Gabriela; Heijnen, Esther; Smolenov, Igor; Dull, Peter M

    2015-01-01

    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].

  12. 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.

    Science.gov (United States)

    Urbancikova, Ingrid; Prymula, Roman; Goldblatt, David; Roalfe, Lucy; Prymulova, Karolina; Kosina, Pavel

    2017-09-12

    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

  13. Development and Use of a Serum Bactericidal Assay Using Pooled Human Complement To Assess Responses to a Meningococcal Group A Conjugate Vaccine in African Toddlers

    OpenAIRE

    Bash, Margaret C.; Lynn, Freyja; Mocca, Brian; Borrow, Ray; Findlow, Helen; Hassan-King, Musa; Preziosi, Marie-Pierre; Idoko, Olubukola; Sow, Samba; Kulkarni, Prasad; LaForce, F. Marc

    2014-01-01

    A meningococcal group A polysaccharide (PS) conjugate vaccine (PsA-TT) has been developed for African countries affected by epidemic meningitis caused by Neisseria meningitidis. Complement-mediated serum bactericidal antibody (SBA) assays are used to assess protective immune responses to meningococcal vaccination. Human complement (hC′) was used in early studies demonstrating antibody-mediated protection against disease, but it is difficult to obtain and standardize. We developed and evaluate...

  14. Invasive pneumococcal disease in Catalonian elderly people, 2002-2009: serotype coverage for different anti-pneumococcal vaccine formulations at the beginning of the new conjugate vaccines era.

    Science.gov (United States)

    Vila-Corcoles, Angel; Ochoa-Gondar, Olga; Gomez-Bertomeu, Frederic; Raga-Luria, Xavier

    2011-10-06

    Population-based surveillance study conducted among persons 65 years or older from the region of Tarragona (Southern Catalonia, Spain) during 2002-2009. All cases with isolation of pneumococcus from normally sterile bodily fluids were included. Incidence rates of invasive pneumococcal disease (IPD) and prevalence of infections caused by serotypes included in different pneumococcal conjugate vaccines (PCVs) and the 23-valent pneumococcal polysaccharide vaccine (PPV-23) were calculated. Overall, 176 IPD cases were observed, which means an incidence of 48 episodes per 100,000 person-year throughout the study period. The most dominant serotypes were 7F (10.1%), 14 (9.4%), 19A (9.4%), 3 (8.6%), 6A (7.9%) and 1 (7.2%). IPD cases due to PCV-7 types (from 37.2% to 14.6%; p=0.003) and PCV-10 types (from 60.5% to 32.3%; p=0.002) considerably decreased between 2002-2005 and 2006-2009 periods. Percentage of cases due to PCV-13 types (76.7% vs 62.5%; p=0.099) and PPV-23 types (81.4% vs 68.8%; p=0.122) did not significantly change between both periods. As main conclusion, in our setting, the PCV-13 has almost similar serotype coverage to the PPV-23 in preventing IPD among the elderly population, which suggests a possible future use of the conjugate vaccine in all age groups. Copyright © 2011 Elsevier Ltd. All rights reserved.

  15. Clinical burden of pneumonia, meningitis and septicemia in Norway 2 years after 7-valent pneumococcal conjugate vaccine introduction.

    Science.gov (United States)

    Munson, Samantha; Raluy-Callado, Mireia; Lambrelli, Dimitra; Wasiak, Radek; Eriksson, Daniel; Gray, Sharon

    2015-08-01

    This population-based, retrospective study quantified the rates of all-cause and pneumococcal pneumonia, meningitis and septicemia in Norway from 2008 to 2009 and determined the proportions of cases caused by pneumococcal vaccine serotypes. Data on patients with all-cause and pneumococcal pneumonia, meningitis and septicemia were obtained from the Norwegian Patient Registry, which collects hospitalization data from all Norwegian public hospitals based on International Classification of Diseases codes. Norwegian Patient Registry case records linked to the Norwegian Surveillance System for Communicable Diseases provided serotype data for invasive pneumococcal disease in patients with microbiological cultures. In 2008 and 2009, hospitalization rates were relatively stable for all-cause pneumonia (5.28 and 5.35, respectively, per 1000), meningitis (10.70 and 9.67, respectively, per 100,000), and septicemia (from 171.81 to 161.46 per 100,000). In contrast, rates decreased for International Classification of Diseases-10 diagnosed pneumococcal pneumonia (from 13.66 to 10.52 per 100,000), although these cases may be under-reported because of inclusion in all-cause pneumonia. Rates also decreased in diagnosed pneumococcal meningitis (from 1.60 to 1.19 per 100,000) and diagnosed pneumococcal septicemia (from 9.08 to 7.94 per 100,000). Diagnosed pneumococcal disease rates were highest in younger children and older adults, peaking at ⩾ 60 years old. Pneumococcal pneumonia, meningitis and septicemia caused by serotypes included in the 7-valent pneumococcal conjugate vaccine decreased substantially during the study period, with corresponding serotype replacement by non-7-valent pneumococcal conjugate vaccine serotypes. From 2008 to 2009, International Classification of Diseases-10 diagnosed pneumococcal pneumonia, meningitis and septicemia decreased in most age groups but remained greatest among subjects aged 0-1 and ⩾ 60 years. © 2015 the Nordic Societies of Public Health.

  16. Nationwide Trends in Bacterial Meningitis before the Introduction of 13-Valent Pneumococcal Conjugate Vaccine-Burkina Faso, 2011-2013.

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    Dinanibè Kambiré

    Full Text Available Following introduction of Haemophilus influenzae type b vaccine in 2006 and serogroup A meningococcal conjugate vaccine in 2010, Streptococcus pneumoniae (Sp became the leading cause of bacterial meningitis in Burkina Faso. We describe bacterial meningitis epidemiology, focusing on pneumococcal meningitis, before 13-valent pneumococcal conjugate vaccine (PCV13 introduction in the pediatric routine immunization program in October 2013.Nationwide population-based meningitis surveillance collects case-level demographic and clinical information and cerebrospinal fluid (CSF laboratory results. Sp infections are confirmed by culture, real-time polymerase chain reaction (rt-PCR, or latex agglutination, and CSF serotyped using real-time and conventional PCR. We calculated incidence rates in cases per 100,000 persons, adjusting for age and proportion of cases with CSF tested at national reference laboratories, and case fatality ratios (CFR.During 2011-2013, 1,528 pneumococcal meningitis cases were reported. Average annual adjusted incidence rates were 26.9 (<1 year, 5.4 (1-4 years, 7.2 (5-14 years, and 3.0 (≥15 years. Overall CFR was 23% and highest among children aged <1 year (32% and adults ≥30 years (30%. Of 1,528 cases, 1,036 (68% were serotyped: 71% were PCV13-associated serotypes, 14% were non-PCV13-associated serotypes, and 15% were non-typeable by PCR. Serotypes 1 (45% and 12F/12A/12B/44/46 (8% were most common. Among children aged <1 year, serotypes 5 (15%, 6A/6B (13% and 1 (12% predominated.In Burkina Faso, the highest morbidity and mortality due to pneumococcal meningitis occurred among children aged <1 year. The majority of cases were due to PCV13-associated serotypes; introduction of PCV13 should substantially decrease this burden.

  17. Immunogenicity and persistence of the 13-valent Pneumococcal Conjugate Vaccine (PCV13 in patients with untreated Smoldering Multiple Myeloma (SMM: A pilot study

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    Mathilde Bahuaud

    2017-11-01

    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

  18. 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.

    Science.gov (United States)

    Leach, Amanda J; Wigger, Christine; Beissbarth, Jemima; Woltring, Donna; Andrews, Ross; Chatfield, Mark D; Smith-Vaughan, Heidi; Morris, Peter S

    2016-07-01

    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

  19. Economic impact of pneumococcal conjugate vaccination in Brazil, Chile, and Uruguay Impacto económico de la vacuna antineumocócica conjugada en Brasil, Chile y Uruguay

    OpenAIRE

    Dagna O. Constenla

    2008-01-01

    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 ra...

  20. Towards the introduction of pneumococcal conjugate vaccines in Bhutan: A cost-utility analysis to determine the optimal policy option.

    Science.gov (United States)

    Dorji, Kinley; Phuntsho, Sonam; Pempa; Kumluang, Suthasinee; Khuntha, Sarayuth; Kulpeng, Wantanee; Rajbhandari, Sneha; Teerawattananon, Yot

    2018-03-20

    Due to competing health priorities and limited resources, many low-income countries, even those with a high disease burden, are not able to introduce pneumococcal conjugate vaccines. To determine the cost-utility of 10- and 13-valent pneumococcal conjugate vaccines (PCV10 and PCV13) compared to no vaccination in Bhutan. A model-based cost-utility analysis was performed in the Bhutanese context using a government perspective. A Markov simulation model with one-year cycle length was used to estimate the costs and outcomes of three options: PCV10, PCV13 and no PCV programmes for a lifetime horizon. A discount rate of 3% per annum was applied. Results are presented using an incremental cost-effectiveness ratio (ICER) in United State Dollar per quality-adjusted life year (QALY) gained (USD 1 = Ngultrum 65). A one-way sensitivity analysis and a probabilistic sensitivity analysis were conducted to assess uncertainty. Compared to no vaccination, PCV10 and PCV13 gained 0.0006 and 0.0007 QALYs with additional lifetime costs of USD 0.02 and USD 0.03 per person, respectively. PCV10 and PCV13 generated ICERs of USD 36 and USD 40 per QALY gained compared to no vaccination. In addition, PCV13 produced an ICER of USD 92 compared with PCV10. When including PCV into the Expanded Programme on Immunization, the total 5-year budgetary requirement is anticipated to increase to USD. 3.77 million for PCV10 and USD 3.75 million for PCV13. Moreover, the full-time equivalent (FTE) of one health assistant would increase by 2.0 per year while the FTE of other health workers can be reduced each year, particularly of specialist (0.6-1.1 FTE) and nurse (1-1.6 FTE). At the suggested threshold of 1xGDP per capita equivalent to USD 2708, both PCVs are cost-effective in Bhutan and we recommend that they be included in the routine immunization programme. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  1. Multiple colonization with S. pneumoniae before and after introduction of the seven-valent conjugated pneumococcal polysaccharide vaccine.

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    Silvio D Brugger

    2010-07-01

    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.

  2. Emerging pneumococcal carriage serotypes in a high-risk population receiving universal 7-valent pneumococcal conjugate vaccine and 23-valent polysaccharide vaccine since 2001

    Directory of Open Access Journals (Sweden)

    Stubbs Liz

    2009-08-01

    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

  3. Characterization of the antibody response to a Haemophilus influenzae type b conjugate vaccine in children with recurrent lower respiratory tract infection

    DEFF Research Database (Denmark)

    Kristensen, K; Barington, T; Pressler, T

    1995-01-01

    once with a Haemophilus influenzae type b (Hib) conjugate vaccine. Total IgG subclasses, total antipolysaccharide Hib antibodies, and antipolysaccharide Hib antibodies of IgM, IgG, IgA, and IgG1-4 specificity were determined by ELISA. There were no significant differences between the two groups in any...

  4. Effect of Reduced-Dose Schedules With 7-Valent Pneumococcal Conjugate Vaccine on Nasopharyngeal Pneumococcal Carriage in Children A Randomized Controlled Trial

    NARCIS (Netherlands)

    van Gils, Elske J. M.; Veenhoven, Reinier H.; Hak, Eelko; Rodenburg, Gerwin D.; Bogaert, Debby; IJzerman, Ed P. F.; Bruin, Jacob P.; van Alphen, Loek; Sanders, Elisabeth A. M.

    2009-01-01

    Context The effects of reduced-dose schedules of 7-valent pneumococcal conjugate vaccine (PCV-7) on pneumococcal carriage in children are largely unknown, although highly relevant in the context of subsequent herd effects. Objective To examine the effects of a 2-dose and 2 + 1-dose PCV-7 schedule on

  5. Immunogenicity of a 7-valent pneumococcal conjugate vaccine (PCV7) and impact on carriage in Venezuelan children at risk of invasive pneumococcal diseases

    NARCIS (Netherlands)

    Rivera-Olivero, I.A.; Nogal, B. del; Fuentes, M.; Cortez, R.; Bogaert, D.; Hermans, P.W.M.; Waard, J.H. de

    2014-01-01

    BACKGROUND AND AIMS: We evaluated the immunogenicity of the 7-valent pneumococcal conjugate vaccine (PCV7), and its impact on pneumococcal carriage in Venezuelan children at high risk for invasive pneumococcal disease (IPD). METHODS: 82 children (age 2-59 months) with sickle cell anemia (n=22),

  6. Immunogenicity and persistence of the 13-valent Pneumococcal Conjugate Vaccine (PCV13) in patients with untreated Smoldering Multiple Myeloma (SMM): A pilot study.

    Science.gov (United States)

    Bahuaud, Mathilde; Bodilis, Hélène; Malphettes, Marion; Maugard Landre, Anaïs; Matondo, Caroline; Bouscary, Didier; Batteux, Frédéric; Launay, Odile; Fermand, Jean-Paul

    2017-11-01

    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.

  7. Introduction and Rollout of a New Group A Meningococcal Conjugate Vaccine (PsA-TT) in African Meningitis Belt Countries, 2010–2014

    Science.gov (United States)

    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

    2015-01-01

    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

  8. The Vi conjugate typhoid vaccine is safe, elicits protective levels of IgG anti-Vi, and is compatible with routine infant vaccines.

    Science.gov (United States)

    Thiem, Vu Dinh; Lin, Feng-Ying C; Canh, Do Gia; Son, Nguyen Hong; Anh, Dang Duc; Mao, Nguyen Duc; Chu, Chiayung; Hunt, Steven W; Robbins, John B; Schneerson, Rachel; Szu, Shousun C

    2011-05-01

    Typhoid fever remains a serious problem in developing countries. Current vaccines are licensed for individuals who are 5 years old or older. A conjugate of the capsular polysaccharide (CP) of Salmonella enterica serovar Typhi (Vi) bound to recombinant exoprotein A of Pseudomonas aeruginosa (Vi-rEPA) enhanced Vi immunogenicity and protected 2- to 5-year-olds in Vietnam. In this study, Vi-rEPA was evaluated for use in infants. A total of 301 full-term Vietnamese infants received Expanded Program on Immunization (EPI) vaccines alone or with Vi-rEPA or Haemophilus influenzae type b-tetanus toxoid conjugate (Hib-TT) at 2, 4, and 6 months and Vi-rEPA or Hib-TT alone at 12 months. Infants were visited 6, 24, and 48 h after each injection to monitor adverse reactions. Maternal, cord, and infant sera were assayed for IgG anti-Vi and for IgG antibodies to Hib CP and the diphtheria, tetanus, and pertussis toxins at 7, 12, and 13 months. No vaccine-related serious adverse reactions occurred. In the Vi-rEPA group, the IgG anti-Vi geometric mean (GM) increased from the cord level of 0.66 to 17.4 enzyme-linked immunosorbent assay units (EU) at 7 months, declined to 4.76 EU at 12 months, and increased to 50.1 EU 1 month after the 4th dose (95% of infants had levels of ≥ 3.5 EU, the estimated protective level). Controls had no increase of the IgG anti-Vi GM. Infants with cord anti-Vi levels of anti-Vi levels than those with levels of ≥ 3.5 EU. Anti-diphtheria, -tetanus, and -pertussis toxin levels were similar in all groups. Vi-rEPA was safe, induced protective anti-Vi levels, and was compatible with EPI vaccines, and it can be used in infants. High cord IgG anti-Vi levels partially suppressed infant responses to Vi-rEPA.

  9. Immunogenicity of a 2-dose priming and booster vaccination with the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine

    DEFF Research Database (Denmark)

    Silfverdal, Sven Arne; Høgh, Birthe; Bergsaker, Marianne Riise

    2009-01-01

    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...

  10. The Typhoid Vaccine Acceleration Consortium (TyVAC): Vaccine effectiveness study designs: Accelerating the introduction of typhoid conjugate vaccines and reducing the global burden of enteric fever. Report from a meeting held on 26-27 October 2016, Oxford, UK.

    Science.gov (United States)

    Meiring, James E; Gibani, Malick

    2017-09-12

    Typhoid fever is estimated to cause between 11.9-26.9 million infections globally each year with 129,000-216,510 deaths. Access to improved water sources have reduced disease incidence in parts of the world but the use of efficacious vaccines is seen as an important public health tool for countries with a high disease burden. A new generation of Vi typhoid conjugate vaccines (TCVs), licensed for use in young children and expected to provide longer lasting protection than previous vaccines, are now available. The WHO Strategic Advisory Group of Experts on Immunization (SAGE) has convened a working group to review the evidence on TCVs and produce an updated WHO position paper for all typhoid vaccines in 2018 that will inform Gavi, the Vaccine Alliance's future vaccine investment strategies for TCVs. The Typhoid Vaccine Acceleration Consortium (TyVAC) has been formed through a $36.9 million funding program from the Bill & Melinda Gates Foundation to accelerate the introduction of TCVs into Gavi-eligible countries. In October 2016, a meeting was held to initiate planning of TCV effectiveness studies that will provide the data required by policy makers and stakeholders to support decisions on TCV use in countries with a high typhoid burden. Discussion topics included (1) the latest evidence and data gaps in typhoid epidemiology; (2) WHO and Gavi methods and data requirements; (3) data on TCV efficacy; (4) cost effectiveness analysis for TCVs from mathematical models; (5) TCV delivery and effectiveness study design. Specifically, participants were asked to comment on study design in 3 sites for which population-based typhoid surveillance is underway. The conclusion of the meeting was that country-level decision making would best be informed by the respective selected sites in Africa and Asia vaccinating children aged from 9-months to 15-years-old, employing either an individual or cluster randomized design with design influenced by population characteristics

  11. Characterization of the antibody response to a Haemophilus influenzae type b conjugate vaccine in children with recurrent lower respiratory tract infection

    DEFF Research Database (Denmark)

    Kristensen, K; Barington, T; Pressler, T

    1995-01-01

    once with a Haemophilus influenzae type b (Hib) conjugate vaccine. Total IgG subclasses, total antipolysaccharide Hib antibodies, and antipolysaccharide Hib antibodies of IgM, IgG, IgA, and IgG1-4 specificity were determined by ELISA. There were no significant differences between the two groups in any...... 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)...

  12. PREVALENCE OF STREPTOCOCCUS PNEUMONIAE SEROTYPES OF THE HEPTAVALENT CONJUGATED VACCINE IN PEDIATRIC INFECTIONS

    Directory of Open Access Journals (Sweden)

    Elena Petraru

    2007-08-01

    Full Text Available Severe evolution of pneumococcal infections with multiresistant strains in children under 2 years of age determined the introduction, in some countries, of the heptavalent vaccine, which includes the most frequent capsular serotypes. The knowledge of serotypes circulating in our area is crucial for the introduction of such a vaccine in our country. We studied 202 pneumococcal strains; out of these, serologic identification of 172 strains established classification in 23 serotypes/15 serogroups; 24 strains were non-typable. 66,3% of isolates belong to serotypes 23F/23B, 6B/6A and 19F/19A. Only 54% of the serotypes isolated from children under 2 years of age are included in the heptavalent vaccine. Pneumococcal strains with high level resistance to beta-lactams and multiresistant to other antibiotics belong to the 2 most frequently isolated serotypes, 19A and 23B. Vaccinal serotypes 4 and 18C were not identified in our study.

  13. Antibody persistence following meningococcal C conjugate vaccination in children and adolescents infected with human immunodeficiency virus

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    Ana Cristina Cisne Frota

    2017-09-01

    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.

  14. Haemophilus influenzae serotype b conjugate vaccine failure in twelve countries with established national childhood immunization programmes.

    Science.gov (United States)

    Ladhani, S; Heath, P T; Slack, M P E; McIntyre, P B; Diez-Domingo, J; Campos, J; Dagan, R; Ramsay, M E

    2010-07-01

    The present study describes the clinical and immunological features of children with Hib vaccine failure, who were identified through national surveillance between 1996 and 2001 in Europe, Israel and Australia. True vaccine failure was defined as invasive Hib disease occurring ≥2 weeks after one dose, given after the first birthday, or ≥1 week after ≥2 doses, given at problem (including prematurity) and 53 out of 161 (33%) had immunoglobulin deficiency. Convalescent Hib antibody concentrations were above the putative protective concentration of 1.0 mg/L in 147/194 (76%) children; low concentrations were associated with both the presence of an underlying medical problem and young age at the time of Hib disease. Almost all children who received an additional vaccine dose developed antibodies at protective concentrations. Thus, Hib vaccine failure is rare, but can occur with any immunization schedule. Children with Hib vaccine failure should have immunoglobulin and convalescent Hib antibody concentrations measured after infection and receive additional vaccination, if required.

  15. 76 FR 53480 - Prospective Grant of Exclusive License: Conjugate Vaccines Against B. anthracis

    Science.gov (United States)

    2011-08-26

    ... toxin, which has 3 components: a receptor-binding protein known as ``protective antigen'' (PA) and 2 catalytic proteins known as ``lethal factor'' (LF) and ``edema factor'' (EF). Although production of an.../0, Schneerson et al., ``Methods for Preparing Immunogenic Conjugates'', U.S. Patent Application...

  16. Estimating the Clinical and Economic Impact of Maintaining use of 13-valent Pneumococcal Conjugate Vaccine (PCV13) in Mexico

    Science.gov (United States)

    Wasserman, Matt; Wilson, Michele; McDade, Cheryl; Grajales, Ana Gabriela; Palacios, Maria Gabriela; Baez- Revueltas, Fabiola Berenice; Farkouh, Raymond

    2017-01-01

    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

  17. [Emergence of invasive pneumococcal disease caused by non-vaccine serotypes in the era of the 7-valent conjugate vaccine].

    Science.gov (United States)

    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

    2014-03-01

    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.

  18. Pneumococcal responses are similar in Papua New Guinean children aged 3-5 years vaccinated in infancy with pneumococcal polysaccharide vaccine with or without prior pneumococcal conjugate vaccine, or without pneumococcal vaccination.

    Directory of Open Access Journals (Sweden)

    Anita H J van den Biggelaar

    Full Text Available In an earlier trial, Papua New Guinean (PNG children at high risk of pneumococcal disease were randomized to receive 0 or 3 doses of 7-valent pneumococcal conjugate vaccine (PCV7, followed by a single dose of 23-valent pneumococcal polysaccharide vaccine (PPV23 at 9 months of age. We here studied in a non-randomized follow-up trial the persistence of pneumococcal immunity in these children at 3-5 years of age (n = 132, and in 121 community controls of a similar age with no prior pneumococcal vaccination.Circulating IgG antibody titers to all PCV7 and PPV23-only serotypes 2, 5 and 7F were measured before and after challenge with 1/5th of a normal PPV23 dose. Serotype-specific memory B-cells were enumerated at 10 months and 3-5 years of age for a subgroup of study children.Serotype-specific IgG antibody titers before and after challenge were similar for children who received PCV7/PPV23, PPV23 only, or no pneumococcal vaccines. Before challenge, at least 89% and 59% of children in all groups had serotype-specific titers ≥ 0.35μg/ml and ≥ 1.0 μg/ml, respectively. Post-challenge antibody titers were higher or similar to pre-challenge titers for most children independent of pneumococcal vaccination history. The rise in antibody titers was significantly lower when pre-challenge titers were higher. Overall the relative number of serotype-specific memory B-cells remained the same or increased between 10 months and 3-5 years of age, and there were no differences in serotype-specific memory B-cell numbers at 3-5 years of age between the three groups.Immunity induced by PCV7 and/or PPV23 immunization in infancy does not exceed that of naturally acquired immunity in 3-5-year-old children living in a highly endemic area. Also, there was no evidence that PPV23 immunization in the first year of life following PCV7 priming induces longer-term hypo-responsiveness.Clinicaltrials.gov NCT01414504 and NCT00219401.

  19. Pneumococcal responses are similar in Papua New Guinean children aged 3-5 years vaccinated in infancy with pneumococcal polysaccharide vaccine with or without prior pneumococcal conjugate vaccine, or without pneumococcal vaccination

    Science.gov (United States)

    Richmond, Peter C.; Fuery, Angela; Anderson, Denise; Opa, Christine; Saleu, Gerard; Lai, Mildred; Francis, Jacinta P.; Alpers, Michael P.; Pomat, William S.; Lehmann, Deborah

    2017-01-01

    Trial design In an earlier trial, Papua New Guinean (PNG) children at high risk of pneumococcal disease were randomized to receive 0 or 3 doses of 7-valent pneumococcal conjugate vaccine (PCV7), followed by a single dose of 23-valent pneumococcal polysaccharide vaccine (PPV23) at 9 months of age. We here studied in a non-randomized follow-up trial the persistence of pneumococcal immunity in these children at 3–5 years of age (n = 132), and in 121 community controls of a similar age with no prior pneumococcal vaccination. Methods Circulating IgG antibody titers to all PCV7 and PPV23-only serotypes 2, 5 and 7F were measured before and after challenge with 1/5th of a normal PPV23 dose. Serotype-specific memory B-cells were enumerated at 10 months and 3–5 years of age for a subgroup of study children. Results Serotype-specific IgG antibody titers before and after challenge were similar for children who received PCV7/PPV23, PPV23 only, or no pneumococcal vaccines. Before challenge, at least 89% and 59% of children in all groups had serotype-specific titers ≥ 0.35μg/ml and ≥ 1.0 μg/ml, respectively. Post-challenge antibody titers were higher or similar to pre-challenge titers for most children independent of pneumococcal vaccination history. The rise in antibody titers was significantly lower when pre-challenge titers were higher. Overall the relative number of serotype-specific memory B-cells remained the same or increased between 10 months and 3–5 years of age, and there were no differences in serotype-specific memory B-cell numbers at 3–5 years of age between the three groups. Conclusions Immunity induced by PCV7 and/or PPV23 immunization in infancy does not exceed that of naturally acquired immunity in 3-5-year-old children living in a highly endemic area. Also, there was no evidence that PPV23 immunization in the first year of life following PCV7 priming induces longer-term hypo-responsiveness. Trial registration Clinicaltrials.gov NCT01414504 and NCT

  20. Impact of ten-valent pneumococcal conjugate vaccination on invasive pneumococcal disease in Finnish children--a population-based study.

    Science.gov (United States)

    Jokinen, Jukka; Rinta-Kokko, Hanna; Siira, Lotta; Palmu, Arto A; Virtanen, Mikko J; Nohynek, Hanna; Virolainen-Julkunen, Anni; Toropainen, Maija; Nuorti, J Pekka

    2015-01-01

    The ten-valent pneumococcal conjugate vaccine (PCV10) was introduced into the Finnish National Vaccination Program (NVP) in September 2010 with a 2+1 schedule (3, 5, 12 months) without catch-up vaccinations. We evaluated the direct and indirect effects of PCV10 on invasive pneumococcal disease (IPD) among children ≤5 years of age during the first three years after NVP introduction. We conducted a population-based, observational follow-up study. The cohort of vaccine-eligible children (all children born June 1, 2010 or later) was followed from 3 months of age until the end of 2013. For the indirect effect, another cohort of older children ineligible for PCV10 vaccination was followed from 2011 through 2013. Both cohorts were compared with season- and age-matched reference cohorts before NVP introduction. National, population-based laboratory surveillance data were used to compare culture-confirmed serotype-specific IPD rates in the vaccine target and reference cohorts by using Poisson regression models. The overall IPD rate among vaccine-eligible children was reduced by 80% (95%CI 72 to 85); the reduction in vaccine-type IPD was 92% (95%CI 86 to 95). However, a non-significant increase in non-vaccine type IPD was observed. During 2012-2013, we also observed a 48% (95%CI 18 to 69) reduction in IPD among unvaccinated children 2 to 5 years of age, which was mostly attributable to the ten vaccine serotypes. This is the first population-based study investigating the impact of PCV10 introduction without prior PCV7 use. A substantial decrease in IPD rates among vaccine-eligible children was observed. A smaller and temporally delayed reduction among older, unvaccinated children suggests that PCV10 also provides indirect protection against vaccine-type IPD. Changes in serotype distribution warrant continuous monitoring of potential increases in non-vaccine serotypes.

  1. Impact of ten-valent pneumococcal conjugate vaccination on invasive pneumococcal disease in Finnish children--a population-based study.

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    Jukka Jokinen

    Full Text Available The ten-valent pneumococcal conjugate vaccine (PCV10 was introduced into the Finnish National Vaccination Program (NVP in September 2010 with a 2+1 schedule (3, 5, 12 months without catch-up vaccinations. We evaluated the direct and indirect effects of PCV10 on invasive pneumococcal disease (IPD among children ≤5 years of age during the first three years after NVP introduction.We conducted a population-based, observational follow-up study. The cohort of vaccine-eligible children (all children born June 1, 2010 or later was followed from 3 months of age until the end of 2013. For the indirect effect, another cohort of older children ineligible for PCV10 vaccination was followed from 2011 through 2013. Both cohorts were compared with season- and age-matched reference cohorts before NVP introduction. National, population-based laboratory surveillance data were used to compare culture-confirmed serotype-specific IPD rates in the vaccine target and reference cohorts by using Poisson regression models.The overall IPD rate among vaccine-eligible children was reduced by 80% (95%CI 72 to 85; the reduction in vaccine-type IPD was 92% (95%CI 86 to 95. However, a non-significant increase in non-vaccine type IPD was observed. During 2012-2013, we also observed a 48% (95%CI 18 to 69 reduction in IPD among unvaccinated children 2 to 5 years of age, which was mostly attributable to the ten vaccine serotypes.This is the first population-based study investigating the impact of PCV10 introduction without prior PCV7 use. A substantial decrease in IPD rates among vaccine-eligible children was observed. A smaller and temporally delayed reduction among older, unvaccinated children suggests that PCV10 also provides indirect protection against vaccine-type IPD. Changes in serotype distribution warrant continuous monitoring of potential increases in non-vaccine serotypes.

  2. Antibody persistence after serogroup C meningococcal conjugate vaccine in children with sickle cell disease.

    Science.gov (United States)

    Souza, Alessandra R; Maruyama, Claudia M; Sáfadi, Marco Aurélio P; Lopes, Marta H; Azevedo, Raymundo S; Findlow, Helen; Bai, Xilian; Borrow, Ray; Weckx, Lily Y

    2016-08-05

    A decline of protective antibody titers after MCC vaccine has been demonstrated in healthy children, this may be an issue of concern for risk groups. The aim of this study was to evaluate the persistence of bactericidal antibodies after MCC vaccine in sickle cell disease (SCD) patients. The type of vaccine used and booster response were also analyzed. SCD patients (n=141) previously immunized with MCC vaccines had blood drawn 2-8 years after the last priming dose. They were distributed according to age at primary immunization into groups: vaccination (2-3, 4-5 and 6-8). Serum bactericidal antibodies with baby rabbit complement (rSBA) and serogroup C-specific IgG concentrations were measured. The correlate of protection was rSBA titer ⩾8. Subjects with rSBA children primed under 2years of age rSBA titer ⩾8 was demonstrated in 53.3%, 21.7% and 35.0%, 2-3, 4-5, 6-8years, respectively, after vaccination, compared with 70.0%, 45.0% and 53.5%, respectively, for individuals primed at ages 2-13years. rSBA median titers and IgG median levels were higher in the older group. Six to eight years after vaccination the percentage of patients with rSBA titers ⩾8 was significantly higher in the group primed with MCC-TT (78.5%) compared with those primed with MCC-CRM197 [Menjugate® (33.3%) or Meningitec® (35.7%)] (p=0.033). After a booster, 98% achieved rSBA titer ⩾8. Immunity to meningococcal serogroup C in SCD children declines rapidly after vaccination and is dependent on the age at priming. Booster doses are needed to maintain protection in SCD patients. Persistence of antibodies seems to be longer in individuals primed with MCC-TT vaccine comparing to those immunized with MCC-CRM197. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Lot-to-lot consistency, safety and immunogenicity of 3 lots of Haemophilus influenzae type b conjugate vaccine: results from a phase III randomized, multicenter study in infants.

    Science.gov (United States)

    Klein, Nicola P; Abu-Elyazeed, Remon; Cornish, Matthew; Leonardi, Michael L; Weiner, Leonard B; Silas, Peter E; Grogg, Stanley E; Varman, Meera; Frenck, Robert W; Cheuvart, Brigitte; Baine, Yaela; Miller, Jacqueline M; Leyssen, Maarten; Mesaros, Narcisa; Roy-Ghanta, Sumita

    2017-06-16

    Vaccination against Haemophilus influenzae type b (Hib) is included in routine pediatric immunization schedule in the United States. Previous vaccine shortages have created the need for additional options for Hib vaccination. This phase III, randomized, multi-centered study (NCT01000974) evaluated the safety and immunogenicity of a monovalent tetanus toxoid-conjugate Hib vaccine (Hib-TT) compared to a monovalent (Hib-TT control) and a combination Hib-TT vaccine. We hierarchically assessed lot-to-lot consistency of 3 Hib-TT lots and non-inferiority of Hib-TT to Hib-TT control. We co-administered routine pediatric vaccines with Hib-TT vaccines at 2, 4, 6months (primary vaccination) and 15-18months of age (booster vaccination). We recorded adverse events (AEs) for 4 (solicited) and 31days (unsolicited) post-vaccination and serious AEs (SAEs) throughout the study. Of 4009 enrolled children, 3086 completed booster phase. Lot-to-lot consistency was not demonstrated. The study met statistical criteria for non-inferiority of Hib-TT to Hib-TT control in terms of immune responses to Hib and co-administered vaccines' antigens, but not in terms of participants achieving post-primary vaccination anti-PRP levels ≥1µg/mL. Because of the hierarchical nature of the objectives, non-inferiority could not be established. In all groups, 92.5-96.7% and 99.6-100% of participants achieved anti-PRP levels ≥0.15µg/mL, while 78.3-89.8% and 97.9-99.1% had anti-PRP levels ≥1µg/mL, post-primary and post-booster vaccination, respectively. Immune responses to co-administered vaccines and reported incidence of AEs were comparable among groups. We recorded SAEs for 107/2963 (3.6%), 24/520 (4.6%), and 21/520 (4.0%) children post-primary vaccination, and 29/2337 (1.2%), 4/435 (0.9%), and 2/400 (0.5%) children post-booster vaccination with Hib-TT, Hib-TT control and combination Hib-TT vaccine, respectively; 6/5330 (0.1%) SAEs in the Hib-TT groups were considered vaccine-related. Hib

  4. Bacterial Meningitis after Cochlear Implantation among Children without Polyvalent Conjugate Vaccine: A Brief Report of an Iranian Cohort Study on 371 Cases.

    Science.gov (United States)

    Afsharpaiman, Shahla; Amirsalari, Susan; Ajalloueyan, Mohammad; Saburi, Amin

    2014-08-01

    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. 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. 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. 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.

  5. Bacterial Meningitis after Cochlear Implantation among Children without Polyvalent Conjugate Vaccine: A Brief Report of an Iranian Cohort Study on 371 Cases

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    Shahla Afsharpaiman

    2014-01-01

    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.

  6. High-affinity memory B cells induced by conjugate vaccines against weak tumor antigens are vulnerable to nonconjugated antigen.

    Science.gov (United States)

    Savelyeva, Natalia; Shipton, Michael; Suchacki, Amy; Babbage, Gavin; Stevenson, Freda K

    2011-07-21

    Induction of antibody-mediated immunity against hematologic malignancies requires CD4(+) T-cell help, but weak tumor antigens generally fail to induce adequate T-cell responses, or to overcome tolerance. Conjugate vaccines can harness alternative help to activate responses, but memory B cells may then be exposed to leaking tumor-derived antigen without CD4(+) T-cell support. We showed previously using lymphoma-derived idiotypic antigen that exposure to "helpless" antigen silences the majority of memory IgG(+) B cells. Transfer experiments now indicate that silencing is permanent. In marked contrast to IgG, most coexisting IgM(+) memory B cells exposed to "helpless" antigen survive. Confirmation in a hapten (NP) model allowed measurement of affinity, revealing this, rather than isotype, as the determinant of survival. IgM(+) B cells had Ig variable region gene usage similar to IgG but with fewer somatic mutations. Survival of memory B cells appears variably controlled by affinity for antigen, allowing a minority of low affinity IgG(+), but most IgM(+), memory B cells to escape deletion in the absence of T-cell help. The latter remain, but the majority fail to undergo isotype switch. These findings could apply to other tumor antigens and are relevant for vaccination strategies aimed to induce long-term antibody.

  7. Trends in pneumococcal meningitis hospitalizations following the introduction of the 13-valent pneumococcal conjugate vaccine in the United States.

    Science.gov (United States)

    Jacobs, David M; Yung, Francine; Hart, Emily; Nguyen, Melanie N H; Shaver, Amy

    2017-10-27

    The 13-valent pneumococcal conjugate vaccine (PCV13) was introduced in 2010 in the U.S. and its impact on pneumococcal meningitis (PM) is unknown. We assessed the impact of PCV13 on PM hospitalization rates 4years after the vaccine was introduced. This was a retrospective analysis of the National Inpatient Sample from 2008-2014. Patients with an ICD-9-CM code for PM (320.1) were identified and rates calculated using US Census data as the denominator. Data weights were used to derive national estimates. We examined three time periods: 2008-2009 (late post-PCV7), 2010 (transition year), and 2011-2014 (post-PCV13). During the study period, there were 10,493 hospitalizations due to PM in the U.S. Overall, PM incidence decreased from 0.62 to 0.38 cases per 100,000 over this time (39% decrease; PFollowing the introduction of PCV13, hospitalization rates for PM decreased significantly with no subsequent improvements in case-fatality rate. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Early effectiveness of heptavalent conjugate pneumococcal vaccination on invasive pneumococcal disease after the introduction in the Danish Childhood Immunization Programme

    DEFF Research Database (Denmark)

    Harboe, Zitta B.; Valentiner-Branth, Palle; Benfield, Thomas

    2010-01-01

    We evaluated the effectiveness of the heptavalent pneumococcal conjugate vaccine (PCV7) on invasive pneumococcal disease (IPD) 1 year after PCV7's introduction in the childhood immunization programme through a nationwide cohort study based on laboratory surveillance data. There was a decline...... in the overall incidence of IPD from 19.4 to 17.1 cases per 100,000 population (incidence rate ratios (IRR) 0.87; 95% confidence interval (CI) [0.81-0.96]), and of meningitis from 1.56 to 1.16 (IRR 0.74; 95% CI [0.57-0.97]) comparing pre-PCV7 (years 2000-2007) and PCV7 (year 2008) periods. In children ..., the incidence decreased from 54 to 23 cases per 100,000 (IRR 0.43; 95% CI [0.29-0.62]) and for vaccine-serotypes from 36.7 to 7.7 (IRR 0.20; 95% CI [0.09-0.38]). The incidence of IPD declined approximately 10% (IRR 0.90; 95% CI [0.84-0.97]) in patients aged >or=2 years. The case fatality was 17% in both periods...

  9. Retrospective economic evaluation of childhood 7-valent pneumococcal conjugate vaccination in Australia: Uncertain herd impact on pneumonia critical.

    Science.gov (United States)

    Newall, A T; Reyes, J F; McIntyre, P; Menzies, R; Beutels, P; Wood, J G

    2016-01-12

    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

  10. 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

    Directory of Open Access Journals (Sweden)

    N.V. Savvina

    2011-01-01

    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.

  11. Optimising assessments of the epidemiological impact in The Netherlands of paediatric immunisation with 13-valent pneumococcal conjugate vaccine using dynamic transmission modelling.

    Science.gov (United States)

    De Cao, Elisabetta; Melegaro, Alessia; Klok, Rogier; Postma, Maarten

    2014-01-01

    This work is the first attempt to quantify the overall effects of a 13-valent pneumococcal conjugate vaccine (PCV13) vaccination programme in the Dutch population taking into account all the direct and indirect effects of the vaccine on invasive pneumococcal disease. Using available Dutch data, a dynamic transmission model for the spread of pneumococci and potential subsequent invasive pneumococcal disease has been adapted to the Dutch setting. Overall, invasive pneumococcal disease cases in the Netherlands are predicted to decrease from a pre-vaccination level of 2623 cases annually to 2475, 2289, 2185, 2179, and 2178 cases annually 5-, 10-, 20-, 30-, and 40-years, respectively, post-vaccination. Therefore, vaccination with PCV13 in the Netherlands is predicted to lower invasive pneumococcal disease cases per year by up to 445 cases in the medium- to long-term. The results are quite robust for the sensitivity analyses performed on the parameters that regulate herd immunity and competition between vaccine and non-vaccine types.

  12. Optimising assessments of the epidemiological impact in The Netherlands of paediatric immunisation with 13-valent pneumococcal conjugate vaccine using dynamic transmission modelling.

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    Elisabetta De Cao

    Full Text Available This work is the first attempt to quantify the overall effects of a 13-valent pneumococcal conjugate vaccine (PCV13 vaccination programme in the Dutch population taking into account all the direct and indirect effects of the vaccine on invasive pneumococcal disease. Using available Dutch data, a dynamic transmission model for the spread of pneumococci and potential subsequent invasive pneumococcal disease has been adapted to the Dutch setting. Overall, invasive pneumococcal disease cases in the Netherlands are predicted to decrease from a pre-vaccination level of 2623 cases annually to 2475, 2289, 2185, 2179, and 2178 cases annually 5-, 10-, 20-, 30-, and 40-years, respectively, post-vaccination. Therefore, vaccination with PCV13 in the Netherlands is predicted to lower invasive pneumococcal disease cases per year by up to 445 cases in the medium- to long-term. The results are quite robust for the sensitivity analyses performed on the parameters that regulate herd immunity and competition between vaccine and non-vaccine types.

  13. A nationwide study on the impact of pneumococcal conjugate vaccination on antibiotic use and ventilation tube insertion in Denmark 2000-2014

    DEFF Research Database (Denmark)

    Howitz, Michael Frantz; Harboe, Zitta Barrella; Ingels, Helene

    2017-01-01

    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...... of antibiotics in the pre-PCV period to a decreasing incidence for all children age 0-15years. The 2.4 DDD per person year in 2014 was at almost the same level of antibiotic use as in 2000 at 2.3 DDD per person year. Similar patterns were observed in the mostly vaccinated age groups below 5years of age. For VTI......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...

  14. Safety, immunogenicity and dose ranging of a new Vi-CRM₁₉₇ conjugate vaccine against typhoid fever: randomized clinical testing in healthy adults.

    Science.gov (United States)

    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

    2011-01-01

    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.

  15. Safety, immunogenicity and dose ranging of a new Vi-CRM₁₉₇ conjugate vaccine against typhoid fever: randomized clinical testing in healthy adults.

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    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.

  16. Hib antibody responses in infants following diphtheria, tetanus, acellular pertussis, and conjugated Haemophilus influenzae type b (Hib) combination vaccines with decreasing amounts of tetanus toxoid.

    Science.gov (United States)

    Bernstein, Henry H; Seyferth, Elisabeth R

    2017-12-04

    While combination vaccines have contributed to improved vaccine uptake rates in children, studies have documented varied immunogenicity to specific vaccine components. We studied whether varying the amount of tetanus toxoid (TT) in a DTaP and Hib combination vaccine would result in immunogenicity comparable with separate, concurrent administration. We evaluated the immunogenicity of Massachusetts Biologic Laboratories (MBL) diphtheria, tetanus, and acellular pertussis (mDTaP) vaccine combined with tetanus-conjugated MBL Haemophilus influenzae type b vaccine (mHib) in a single injection (DTaPH). We compared four DTaPH vaccines containing varying concentrations of TT. We also evaluated the immune response to the DTaP vaccine manufactured by Connaught Laboratories (now known as Sanofi Pasteur) given with mHib and with Wyeth Hib-CRM 197 (HbOC) as separate injections. Vaccines were administered to 240 healthy infants at 2, 4, and 6 months of age, and blood specimens for antibody determination were obtained before each immunization and one month after the third immunization. We found no significant differences in immune response to the vaccines between the four DTaPH groups. Hib antibody responses were similar in the mHib and the HbOC groups but significantly lower in the DTaPH groups, as measured by Chinese Hamster Ovary (CHO) cell neutralization titers and filamentous hemagglutinin antigen (FHA) geometric mean concentrations (GMC) of anti-Hib antibodies. There were no significant differences between the groups in pertussis or tetanus toxoid antibody levels. Reducing tetanus toxoid amounts did not produce comparable immunogenicity for Hib. The nature of the interaction between immune responses to DTaPH components should be explored further to enable the development of better Hib-containing combination vaccines. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Serotype-specific changes in invasive pneumococcal disease after pneumococcal conjugate vaccine introduction: a pooled analysis of multiple surveillance sites.

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    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

  18. Safety Monitoring in Group A Meningococcal Conjugate Vaccine Trials: Description, Challenges, and Lessons.

    Science.gov (United States)

    Enwere, Godwin C; Paranjape, Gandhali; Kulkarni, Prasad S; Ginde, Manisha; Hartmann, Katharina; Viviani, Simonetta; Chaumont, Julie; Martellet, Lionel; Makadi, Marie-Francoise; Ivinson, Karen; Marchetti, Elisa; Herve, Jacques; Kertson, Kim; LaForce, F Marc; Preziosi, Marie-Pierre

    2015-11-15

    The determination of the safety profile of any vaccine is critical to its widespread use in any population. In addition, the application of international guidelines to fit local context could be a challenging but important step toward obtaining quality safety data. In clinical studies of PsA-TT (MenAfriVac), safety was monitored immediately after vaccination, at 4-7 days for postimmunization local and systemic reactions, within 28 days for adverse events, and throughout the duration of study for serious adverse events. Initial and ongoing training of sites' staff were undertaken during the studies, and a data and safety monitoring board reviewed all the data during and after the studies. The safety of PsA-TT was evaluated according to international standards despite obvious challenges in remote areas where these studies were conducted. These challenges included the need for uniformity of methods, timely reporting in the context of frequent communication problems, occurrence of seasonal diseases such as malaria and rotavirus diarrhea, and healthcare systems that required improvement. The trials of PsA-TT highlighted the value of a robust vaccine development plan and design so that lessons learned in initial studies were incorporated into the subsequent ones, initial training and periodic retraining, strict monitoring of all procedures, and continuous channel of communication with all stakeholders that enabled the application of international requirements to local settings, with high quality of data. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

  19. Impact of Pneumococcal Conjugate Universal Routine Vaccination on Pneumococcal Disease in Italian Children

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    Francesca Fortunato

    2015-01-01

    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.

  20. Development of chitosan conjugated DNA vaccine against nodavirus in Macrobrachium rosenbergii (De Man, 1879).

    Science.gov (United States)

    Ramya, V L; Sharma, R; Gireesh-Babu, P; Patchala, S R; Rather, A; Nandanpawar, P C; Eswaran, S

    2014-09-01

    The protective efficacy of a DNA construct containing extra small virus antisense (XSVAS) gene of nodavirus encapsulated with chitosan nanoparticles (NPs) was investigated in giant freshwater prawn Macrobrachium rosenbergii (De Man, 1879). The delivery was carried out using oral and immersion methods. A plasmid concentration of 100 ng μL(-1) when conjugated with chitosan NPs was found to be more effective in increasing the survivability of the infected prawn. The particle mean size, zeta potential and loading efficiency percentage were 297 nm, 27 mV and 85%, respectively. The ability of the chitosan to form a complex with the plasmid was studied by agarose gel electrophoresis. The NPs were characterized by atomic force microscopy (AFM). Persistence study showed the presence of the DNA construct up to 30th day post-treatment. The oral treatment was found to be better than the immersion treatment for delivery of the chitosan-conjugated DNA construct. This is probably the first report on the delivery of nanoconjugated DNA construct in M. rosenbergii, against nodavirus. © 2013 John Wiley & Sons Ltd.

  1. Stimulation of protective antibodies against type Ia and Ib group B streptococci by a type Ia polysaccharide-tetanus toxoid conjugate vaccine.

    OpenAIRE

    Wessels, M R; Paoletti, L C; Rodewald, A K; Michon, F; DiFabio, J; Jennings, H J; Kasper, D L

    1993-01-01

    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...

  2. Immunogenicity and safety of single-dose, 13-valent pneumococcal conjugate vaccine in pediatric and adolescent oncology patients.

    Science.gov (United States)

    Hung, Te-Yu; Kotecha, Rishi S; Blyth, Christopher C; Steed, Sarah K; Thornton, Ruth B; Ryan, Anne L; Cole, Catherine H; Richmond, Peter C

    2017-11-01

    Children receiving immunosuppressive treatment for cancer are at high risk for invasive pneumococcal disease. The 13-valent pneumococcal conjugate vaccine (PCV13) can prevent pneumococcal disease in healthy children; however, there is an absence of literature regarding the benefit of PCV13 in immunocompromised children with cancer. A prospective, open-label cohort study recruited children between ages 1 and 18 years who were receiving active immunosuppressive therapy (AIT) or were within 12 months after completing immunosuppressive therapy (CIT). Blood samples were taken before and 4 weeks after the administration of single-dose PCV13. Serotype-specific immunoglobulin G antibody titers were measured, and titers ≥0.35 μg/mL were considered protective. Solicited side effects were recorded in a 7-day diary after vaccination. Eighty-five children were recruited. At baseline, ≤50% had protective antibody titers against Streptococcus pneumoniae for 10 serotypes in the AIT group and for 8 serotypes in the CIT group. Postvaccination, ≥70% had protective antibody titers for 9 and 11 serotypes in the AIT and CIT groups, respectively. Both groups had comparable responses to PCV7 serotypes, whereas a significantly higher proportion in the CIT group achieved protective antibody titers to PCV13 serotypes. There was a low rate of serious adverse events (3.5%). A single-dose of PCV13 is safe and immunogenic in children diagnosed with cancer. All children who are receiving therapy for cancer should receive a single dose of PCV13 as soon as possible after diagnosis, regardless of prior PCV exposure. The current data support the recommendation for an additional dose of PCV13 after the completion of immunosuppressive therapy to provide additional protection against invasive pneumococcal disease. Cancer 2017;123:4215-4223. © 2017 American Cancer Society. © 2017 American Cancer Society.

  3. Changes in the Nature and Severity of Invasive Pneumococcal Disease in Children Before and After the Seven-valent and Thirteen-valent Pneumococcal Conjugate Vaccine Programs in Calgary, Canada.

    Science.gov (United States)

    Ricketson, Leah J; Conradi, Nicholas G; Vanderkooi, Otto G; Kellner, James D

    2018-01-01

    Since the introduction of childhood pneumococcal conjugate vaccines, invasive pneumococcal disease (IPD) incidence has decreased in children and the predominant serotypes causing disease have changed. This study describes changes in the clinical features of IPD in children (vaccine introduction. The Calgary Area Streptococcus pneumoniae Epidemiology Research study collects information on all IPD cases in Calgary, Alberta, Canada. Descriptive and regression analyses were used to compare IPD in the pre-vaccine (January 2000 to August 2002), post-7-valent protein-polysaccharide conjugate vaccine (September 2002 to June 2010) and post-13-valent protein-polysaccharide conjugate vaccine (PCV13) (July 2010 to December 2015) periods; intensive care unit and inpatient admissions were outcome measures. The incidence of IPD in children (children presenting with IPD shifted from 2.0 years (interquartile range: 2.5) in the pre-vaccine period to 3.9 years (interquartile range: 6.2) in the post-PCV13 period. The proportion of children with a comorbidity that is an indication for pneumococcal vaccination did not change. Invasive disease with focus (meningitis, pneumonia, empyema, peritonitis) compared with invasive disease with bacteremia only increased from 44.6% in pre-vaccine to 64.0% and 61.4% in the post-7-valent protein-polysaccharide conjugate vaccine and post-PCV13 periods, respectively (P = 0.017). Having IPD in the post-PCV13 period compared with the pre-vaccine period was associated with an increased odds of hospitalization [Odds ratio (OR): 2.9; 95% Confidence Interval (CI): 1.4-6.2]. Clinical features of IPD have changed since pneumococcal conjugate vaccines were introduced, with a shift toward more focal infections requiring hospitalization. Although overall IPD cases have declined, disease that does occur appears to be more severe.

  4. Immunogenicity and safety of measles-mumps-rubella and varicella vaccines coadministered with a fourth dose of Haemophilus influenzae type b and Neisseria meningitidis serogroups C and Y-tetanus toxoid conjugate vaccine in toddlers: a pooled analysis of randomized trials.

    Science.gov (United States)

    Bryant, Kristina; McVernon, Jodie; Marchant, Colin; Nolan, Terry; Marshall, Gary; Richmond, Peter; Marshall, Helen; Nissen, Michael; Lambert, Stephen; Aris, Emmanuel; Mesaros, Narcisa; Miller, Jacqueline

    2012-08-01

    A pooled analysis was conducted of 1257 toddlers who received a fourth dose of Haemophilus influenzae type b-Neisseria meningitidis serogroups C and Y-tetanus toxoid conjugate vaccine (HibMenCY-TT) or Hib conjugate vaccine (Hib polysaccharide conjugated to N. meningitidis outer membrane protein) coadministered with measles-mumps-rubella (MMR) and varicella (VAR) vaccines (NCT00134719/NCT00289783). Noninferiority of immunological responses to MMR and VAR was demonstrated between groups and incidences of MMR- and VAR-specific solicited symptoms were similar, indicating that HibMenCY-TT can be coadministered with MMR and VAR.

  5. Immunogenicity and effectiveness of Haemophilus influenzae type b conjugate vaccine in HIV infected and uninfected African children.

    Science.gov (United States)

    Madhi, Shabir A; Kuwanda, Locadiah; Saarinen, Leena; Cutland, Clare; Mothupi, Rosalia; Käyhty, Helena; Klugman, Keith P

    2005-12-01

    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.

  6. 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

    NARCIS (Netherlands)

    Van Den Bergh, Menno R.; Spijkerman, Judith; François, Nancy; Swinnen, Kristien; Borys, Dorota; Schuerman, Lode; Veenhoven, Reinier H.; Sanders, Elisabeth A M

    2016-01-01

    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

  7. Conjugated nanoliposome with the HER2/neu-derived peptide GP2 as an effective vaccine against breast cancer in mice xenograft model.

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    Atefeh Razazan

    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.

  8. [Evaluation of safety of haemophilus influenza type b(Hib) conjugate vaccine in postmarketing based on the immunization information management system].

    Science.gov (United States)

    Wang, Zhiguo; Ma, Fubao; Zhang, Jinlin; Yu, Jing; Kang, Guodong; Gao, Jun

    2015-06-01

    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

  9. Functional anti-polysaccharide IgG titres induced by unadjuvanted pneumococcal-conjugate vaccine when delivered by microprojection-based skin patch.

    Science.gov (United States)

    Pearson, Frances E; Muller, David A; Roalfe, Lucy; Zancolli, Marta; Goldblatt, David; Kendall, Mark A F

    2015-11-27

    Adequate access to effective and affordable vaccines is essential for the prevention of mortality due to infectious disease. Pneumonia--a consequence of Streptococcus pneumoniae infection--is the world's leading cause of death in children aged under 5 years. The development of a needle-free, thermostable pneumococcal-conjugate vaccine (PCV) could revolutionise the field by reducing cold-chain and delivery constraints. Skin patches have been used to deliver a range of vaccines, with some inducing significantly higher vaccine-specific immunogenicity than needle-injected controls in pre-clinical models, though they have yet to be used to deliver a PCV. We dry-coated a licensed PCV onto a microprojection-based patch (the Nanopatch) and delivered it to mouse skin. We analysed resulting anti-polysaccharide IgG responses. With and without adjuvant, anti-polysaccharide IgG titres induced by Nanopatch immunisation were significantly higher than dose-matched intramuscular controls. These improved responses were primarily obtained against pneumococcal serotypes 4 and 14. Importantly, capsule-specific IgG correlated with functionality in an opsonophagocytic killing assay. We demonstrate enhanced anti-PCV immunogenicity when delivered by Nanopatch over intramuscular injection. As the first study of a PCV delivered by a skin vaccination technology, this report indicates the potential for reduced costs and greater global distribution of such a vaccine. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Molecular characterization of invasive meningococcal isolates from countries in the African meningitis belt before introduction of a serogroup A conjugate vaccine.

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    Dominique A Caugant

    Full Text Available BACKGROUND: The serogroup A conjugate meningococcal vaccine, MenAfriVac, was introduced in mass vaccination campaigns in December 2010 in Burkina Faso, Mali and Niger. In the coming years, vaccination will be extended to other African countries at risk of epidemics. To document the molecular characteristics of disease-causing meningococcal strains circulating in the meningitis belt of Africa before vaccine introduction, the World Health Organization Collaborating Centers on Meningococci in Europe and United States established a common strain collection of 773 isolates from cases of invasive meningococcal disease collected between 2004 and 2010 from 13 sub-Saharan countries. METHODOLOGY: All isolates were characterized by multilocus sequence typing, and 487 (62% were also analyzed for genetic variation in the surface antigens PorA and FetA. Antibiotic susceptibility was tested for part of the collection. PRINCIPAL FINDINGS: Only 19 sequence types (STs belonging to 6 clonal complexes were revealed. ST-5 clonal complex dominated with 578 (74.8% isolates. All ST-5 complex isolates were remarkably homogeneous in their PorA (P1.20,9 and FetA (F3-1 and characterized the serogroup A strains which have been responsible for most epidemics during this time period. Sixty-eight (8.8% of the 773 isolates belonged to the ST-11 clonal complex which was mainly represented by serogroup W135, while an additional 38 (4.9% W135 isolates belonged to the ST-175 complex. Forty-eight (6.2% serogroup X isolates from West Africa belonged to the ST-181 complex, while serogroup X cases in Kenya and Uganda were caused by an unrelated clone, ST-5403. Serogroup X, ST-181, emerged in Burkina Faso before vaccine introduction. CONCLUSIONS: In the seven years preceding introduction of a new serogroup A conjugate vaccine, serogroup A of the ST-5 clonal complex was identified as the predominant disease-causing strain.

  11. Efficacy and safety of vi-tetanus toxoid conjugated typhoid vaccine (PedaTyph™) in Indian children: School based cluster randomized study.

    Science.gov (United States)

    Mitra, Monjori; Shah, Nitin; Ghosh, Apurba; Chatterjee, Suparna; Kaur, Iqbal; Bhattacharya, Nisha; Basu, Suparna

    2016-04-02

    Vi polysaccharide typhoid vaccines cannot be used in children tetanus toxoids (Vi-TT) induces protective levels even in children <2 years. We evaluated efficacy and 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.

  12. Pneumonia hospitalisations in Scotland following the introduction of pneumococcal conjugate vaccination in young children.

    Science.gov (United States)

    Nair, Harish; Watts, Arun Thor; Williams, Linda J; Omer, Saad B; Simpson, Colin R; Willocks, Lorna J; Cameron, J Claire; Campbell, Harry

    2016-08-09

    Scotland introduced PCV7 and PCV13 immunisation in young children in 2006 and 2010 respectively. One recent study from the United States reported a decrease in hospitalisation rates for all-cause pneumonia most notably in adults older than 75 years of age following PCV7 introduction in the US child population. We aimed to examine the effect of PCV7 and PCV13 on hospitalisation rates for all-cause pneumonia across all age groups in Scotland. We linked hospital records and death certification datasets for the entire Scottish population for the period 2000 to 2012. We included all cases where the primary / secondary diagnosis was pneumonia. Differences in hospital admission rates for pneumonia by age group were calculated using the difference in average annual rates for each period. We estimated that all-cause pneumonia hospitalisation rates in children 75 years. At the same time, the median length of hospital stay decreased by a third in children 75 years in the post-PCV13 period compared to the pre-PCV period. Additionally, there was an 11 % reduction in deaths due to all-cause pneumonia, and 30 % reduction in pneumococcal hospitalisations across all age groups in the post-PCV13 period compared with pre-PCV period. The modest and sustained decline in the rates of hospitalisation for all-cause pneumonia in children and the reduction in proportion of pneumonia hospitalisations in children coded as pneumococcal disease in the post-PCV period should alleviate concerns that pneumococcal serotype replacement may have resulted in an increased pneumonia burden in this age group. The indirect impact of child PCV immunisation in those not vaccinated (in terms of reduction in all-cause pneumonia hospitalisations in the elderly) has not been seen in Scotland. Our results are likely to be confounded by changes in clinical coding and healthcare practices over the same period. Our results illustrate that health care planners cannot, with confidence, predict indirect PCV

  13. Evolution of pneumococcal infections in adult patients during a four-year period after vaccination of a pediatric population with 13-valent pneumococcal conjugate vaccine

    Directory of Open Access Journals (Sweden)

    Antoni Payeras

    2015-04-01

    Conclusions: Although a reduction in infections due to vaccine serotypes was observed, close to half of infections in adult patients were caused by PCV-13 serotypes. Even after pediatric vaccination with PCV-13, vaccine serotypes were still responsible for most pneumonia and invasive disease, underscoring the importance of implementing current guidelines and extending vaccination to other risk groups.

  14. A qualitative study on knowledge, perceptions, and attitudes of mothers and health care providers toward pneumococcal conjugate vaccine in Bandung, West Java, Indonesia.

    Science.gov (United States)

    Harjaningrum, Agnes Tri; Kartasasmita, Cissy; Orne-Gliemann, Joanna; Jutand, Marthe-Aline; Goujon, Nicolas; Koeck, Jean-Louis

    2013-03-01

    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.

  15. Risk of Injection-Site Abscess among Infants Receiving a Preservative-Free, Two-Dose Vial Formulation of Pneumococcal Conjugate Vaccine in Kenya

    Science.gov (United States)

    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.

    2015-01-01

    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

  16. Comparison of serum bactericidal and antibody titers induced by two Haemophilus influenzae type b conjugate vaccines: A phase III randomized double-blind study.

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    Akeda, Yukihiro; Koizumi, Yuka; Takanami, Yohei; Sumino, Shuji; Hattori, Yumi; Sugizaki, Kayoko; Mitsuya, Nodoka; Oishi, Kazunori

    2018-03-14

    Haemophilus influenzae type b (Hib) conjugate vaccines have drastically reduced disease incidence worldwide. Protection against Hib infection has relied on the serum bactericidal activity (SBA) of antibodies to the Hib capsular polysaccharide (polyribosylribitol phosphate). However, licensure usually relies on measuring induction of antibodies to PRP as a surrogate for SBA. In a phase III clinical trial we compared a PRP-conjugate vaccine using the nontoxic diphtheria toxin mutant, CRM 197 , as carrier protein with the licensed tetanus toxoid conjugate when administered subcutaneously as a three dose primary series in Japanese infants. As an addition to the phase III study, we have now evaluated SBA and show PRP-CRM 197 induces higher levels of SBA than PRP-T four weeks after the primary series, with a statistically significant correlation with anti-PRP titers. This data confirms the superior immunogenicity of PRP-CRM 197 compared with PRP-T assessed as SBA following a three-dose primary series by subcutaneous administration. Clinical trial registry: Registered on ClinicalTrials.gov (NCT01379846). Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  17. Emergence of antibiotic-resistant non-vaccine serotype pneumococci in nasopharyngeal carriage in children after the use of extended-valency pneumococcal conjugate vaccines in Korea.

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    Choe, Young June; Lee, Hoan Jong; Lee, Hyunju; Oh, Chi Eun; Cho, Eun Young; Choi, Jae Hong; Kang, Hyun Mi; Yoon, In Ae; Jung, Hyun Joo; Choi, Eun Hwa

    2016-09-14

    This study was performed to assess the serotype distribution and antibiotic nonsusceptibility of pneumococcal carriage isolates from children in Korea following the introduction of extended-valency pneumococcal conjugate vaccines (PCVs). From April to June 2014, nasopharyngeal swabs were collected from children who were attending daycare centers in Korea. The collection was conducted in accordance with the World Health Organization Pneumococcal Carriage Working Group standards. Isolates were identified based on colony morphology, the presence of alpha-hemolysis, and inhibition by optochin test. Serotype was determined by Quellung reaction and sequencing analysis (for serogroup 6). The E-test was performed to determine antibiotic susceptibility. A total of 267 pneumococcal isolates were collected from 734 children. Non-PCV13 serotypes accounted for 88.3% and 23A (12.6%), 15B (10.4%), and 15C (9.5%) were most common. Younger age was associated with higher carriage (65.6% vs. 31.2%, Pvaccination was associated with lower carriage caused by PCV13 serotypes (7.4% vs. 20.8%, P=0.007). Overall, nonsusceptibility rates were 86.0% to penicillin and 90.5% to erythromycin, with a multidrug resistance rate of 81.5%. Among penicillin-nonsusceptible isolates, those caused by PCV13 serotypes were 11% and non-PCV13 serotypes were 89%. Frequent non-PCV13 serotypes (23A, 15B, and 15C) were all nonsusceptible to both penicillin and erythromycin except one. High rates of carriage caused by non-PCV13 serotypes such as 23A, 15B, and 15C that show nonsusceptibilities to penicillin and erythromycin were noted following the introduction of extended-valency PCVs in Korea. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Safety and immunogenicity of neonatal pneumococcal conjugate vaccination in Papua New Guinean children: a randomised controlled trial.

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    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.

  19. Etiology of pediatric pneumonia with effusion in the Dominican Republic and potential impact of pneumococcal conjugate vaccines

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    Jesús Feris-Iglesias

    2014-03-01

    Full Text Available Pleural effusion is a serious complication of pneumonia, and Streptococcus pneumoniae is a leading cause. We describe the aetiology of pneumonia with effusion among children in the Dominican Republic before the introduction of the 13-valent pneumococcal conjugate vaccine (PCV in 2013 and the performance characteristics of a rapid immunochromatographic test (ICT for detecting S. pneumoniae in pleural fluid. From July 2009 to June 2011, we enrolled children <15 years old admitted with pneumonia and pleural effusion to Robert Reid Cabral Children’s Hospital, Dominican Republic. Pleural fluid was tested by culture, polymerase chain reaction (PCR for bacterial (S. pyogenes, S. pneumoniae and viral (respiratory syncytial virus and human rhinovirus pathogens, and by ICT for S. pneumoniae. We calculated the performance of ICT and culture compared with PCR. Among 121 cases, the median age was 31 months (range 1 week to 14 years. Pleural fluid culture (n = 121 and PCR testing (n = 112 identified an aetiology in 85 (70.2% cases, including 62 S. pneumoniae (51.2% and 19 Staphylococcus aureus (15.7%. The viruses tested were not detected. The most prevalent pneumococcal serotypes were 14 (n = 20, 1 (n = 13, and 3 (n = 12. Serotype coverage of the 10- and 13-valent PCVs would be 70.5% and 95.1%, respectively. The sensitivity of point-of-care ICT was 100% (95% confidence interval [CI] 94.1% - 100%, while specificity was 86.3% (95% CI 73.7% - 94.3%. S. pneumoniae caused more than half of paediatric pneumonia with effusion cases; introduction of PCV in the Dominican Republic could reduce the burden by 36-49%. ICT is a practical, valid diagnostic tool for clinical care and surveillance in settings with limited laboratory capacity

  20. Decrease in Pneumococcal Otitis Media Cultures With Concomitant Increased Antibiotic Susceptibility in the Pneumococcal Conjugate Vaccines Era.

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    Jabarin, Basel; Pitaro, Jacob; Lazarovitch, Tzilia; Gavriel, Haim; Muallem-Kalmovich, Limor; Eviatar, Ephraim; Marom, Tal

    2017-07-01

    To study the change in the incidence and antibiotic susceptibility patterns of Streptococcus pneumoniae (Spn) in cultures obtained from children with otitis media (OM) during the pneumococcal conjugate vaccines (PCVs) era. Retrospective. Secondary medical care center. Children less than 8 years who presented with OM and had positive pneumococcal cultures during January 1, 2007 to December 12, 2014 were identified. Data recorded included demographics, preadmission antibiotics, culture source, and antibiotic susceptibility tests. We compared the pre-PCV years (2007-2008) with the transition years (2009-2011) and the post-PCV13 years (2012-2014). PCV7 (2009), PCV13 (2010), therapeutic. Annual rate of Spn cultures, antibiotic susceptibility patterns. We identified 134 children (76 boys, 57%) who contributed 162 pneumococcal cultures. There was a downward trend in the annual incidence rate of Spn cultures between the pre-PCV years, transition years, and post-PCV13 years: 11.12, 8.48, and 4.11/1000 hospitalized children/year, respectively (p = 0.08, p = 0.04). Had there been no interventions, and based on the 2007 to 2009 average, the observed over the expected Spn cultures ratio rates for 2010 to 2014 were 0.59, 0.45, 0.40, 0.40, and 0.25, respectively. In parallel, the susceptibility of Spn strains to four commonly tested antibiotics significantly increased from the pre-PCV years to the transition years and the post-PCV13 years. In each period, Spn strains were penicillin sensitive in 37, 51, and 100%; for erythromycin, 46, 71, and 82%; for trimethoprim/sulfamethoxazole, 32, 71, and 97%; and for ceftriaxone, 95, 96, and 100%, respectively. The introduction of PCVs significantly decreased the incidence rate of pneumococcal OM, and increased Spn susceptibility to common antibiotics.

  1. Population snapshot of Streptococcus pneumoniae causing invasive disease in South Africa prior to introduction of pneumococcal conjugate vaccines.

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    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.

  2. Age-dependent prevalence of nasopharyngeal carriage of streptococcus pneumoniae before conjugate vaccine introduction: a prediction model based on a meta-analysis.

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    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.

  3. Age-dependent prevalence of nasopharyngeal carriage of streptococcus pneumoniae before conjugate vaccine introduction: a prediction model based on a meta-analysis.

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    Le Polain de Waroux, Olivier; Flasche, Stefan; Prieto-Merino, David; Edmunds, W John

    2014-01-01

    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.

  4. Association of serum bactericidal antibody and opsonic antibody levels after Neisseria meningitidis serogroup C conjugate vaccine in Brazilian children and adolescents infected or not infected with HIV.

    Science.gov (United States)

    Pereira-Manfro, Wânia F; Alvino, Raquel M; Cruz, Aline C; Silva, Giselle P; Castro, Raquel B N; Ferreira, Bianca; Barreto, Daniella M; Frota, Ana Cristina C; Hofer, Cristina B; Milagres, Lucimar G

    2016-12-07

    Neisseria meningitidis serogroup C (MenC) is the main causative agent of meningitis in Brazil. HIV infection affects the quality of the immune system. HIV + children have an increased risk of infection to encapsulated bacteria such as N. meningitidis. We evaluated the opsonic antibody (OPA) levels and its correlation with serum bactericidal antibody (SBA) levels induced by one and two doses of a MenC conjugate vaccine in children and adolescents HIV + and HIV-exposed but uninfected children (HEU) group. Overall the data show the importance of two doses of vaccine for HIV + individuals. About 79% and 58% of HIV + patients showed SBA and OPA positive response after two doses of vaccine, respectively. For HEU group, 62% and 41% of patients showed SBA and OPA positive response after one dose of vaccine, respectively. A positive and significant association between SBA and OPA levels was seen after two doses of vaccine in HIV + patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. 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

    Science.gov (United States)

    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

    2015-01-01

    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. PMID:25830489

  6. Synthesis of antifungal vaccines by conjugation of β-1,2 trimannosides with T-cell peptides and covalent anchoring of neoglycopeptide to tetanus toxoid.

    Science.gov (United States)

    Cartmell, Jonathan; Paszkiewicz, Eugenia; Dziadek, Sebastian; Tam, Pui-Hang; Luu, Thanh; Sarkar, Susmita; Lipinski, Tomasz; Bundle, David R

    2015-02-11

    Selective strategies for the construction of novel three component glycoconjugate vaccines presenting Candida albicans cell wall glycan (β-1,2 mannoside) and polypeptide fragments on a tetanus toxoid carrier are described. The first of two conjugation strategies employed peptides bearing an N-terminal thiopropionyl residue for conjugation to a trisaccharide equipped with an acrylate linker and a C-terminal S-acetyl thioglycolyl moiety for subsequent linking of neoglycopeptide to bromoacetylated tetanus toxoid. Michael addition of acrylate trisaccharides to peptide thiol under mildly basic conditions gave a mixture of N- and C- terminal glyco-peptide thioethers. An adaptation of this strategy coordinated S-acyl protection with anticipated thioester exchange equilibria. This furnished a single chemically defined fully synthetic neoglycopeptide conjugate that could be anchored to a tetanus toxoid carrier and avoids the introduction of exogenous antigenic groups. The second strategy retained the N-terminal thiopropionyl residue but replaced the C-terminal S-acetate functionality with an azido group that allowed efficient, selective formation of neoglycopeptide thioethers and subsequent conjugation of these with propargylated tetanus toxoid, but introduced potentially antigenic triazole linkages. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. 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.

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    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

    2014-10-02

    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

  8. 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.

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    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

    2016-08-05

    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

  9. Differential regulation of polysaccharide-specific antibody responses to isolated polysaccharides, conjugate vaccines, and intact Gram-positive versus Gram-negative extracellular bacteria.

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    Snapper, Clifford M

    2016-06-24

    Bacterial capsular polysaccharides are major virulence factors and are key targets in a number of licensed anti-bacterial vaccines. Their major characteristics are their large molecular weight and expression of repeating antigenic epitopes that mediate multivalent B cell receptor cross-linking. In addition, since the majority of these antigens cannot associate with MHC-II they fail to recruit CD4+ T cell help and are referred to as T cell-independent antigens. In this review I will discuss a series of studies from my laboratory that have underscored the importance of understanding polysaccharide-specific antibody responses within the context in which the PS is expressed (i.e. in isolation, as a component of conjugate vaccines, and expressed naturally by intact bacteria). We have shown that multivalent B cell receptor crosslinking, as mediated by polysaccharides, uniquely determines the qualitative response of the B cell to subsequent stimuli, but by itself is insufficient to induce antibody secretion or class switching. For these latter events to occur, second signals must act in concert with primary signals derived from the B cell receptor. The co-expression of polysaccharide and protein within intact bacteria promotes recruitment of CD4+ T cell help for the associated PS-specific IgG response, in contrast to isolated polysaccharides. Further, the particulate nature of extracellular bacteria confers properties to the polysaccharide-specific IgG response that makes it distinct immunologically from soluble conjugate vaccines. Finally, the underlying biochemical and/or structural differences that distinguish Gram-positive and Gram-negative bacteria appear to play critical roles in differentially regulating the associated polysaccharide-specific IgG responses to these groups of pathogens. These studies have a number of implications for the understanding and future design of polysaccharide-based vaccines. Published by Elsevier Ltd.

  10. Pneumonia prevention: Cost-effectiveness analyses of two vaccines among refugee children aged under two years, Haemophilus influenzae type b-containing and pneumococcal conjugate vaccines, during a humanitarian emergency, Yida camp, South Sudan.

    Science.gov (United States)

    Gargano, Lisa M; Hajjeh, Rana; Cookson, Susan T

    2017-01-11

    By September 2013, war between Sudan and South Sudan resulted in >70,000 Sudanese refugees and high pneumonia incidence among the 20,000 refugees in Yida camp, South Sudan. Using Médecins Sans Frontières (MSF)-provided data and modifying our decision-tree models, we estimated if administering Haemophilus influenzae type b (Hib)-containing (pentavalent vaccine, also with diphtheria pertussis and tetanus [DPT] and hepatitis B) and pneumococcal conjugate (PCV) vaccines were cost-effective against hospitalized pneumonia. Among children vaccination, one- and two-doses of combined Hib-containing and PCV would avert an estimated 118 and 125 pneumonia cases, and 8.5 and 9.1 deaths, respectively. The cost per Disability-Adjusted-Life-Year averted for administering combined one- and two-doses was US$125 and US$209, respectively. MSF demonstrated that it was possible to administer these vaccines during an emergency and our analysis found it was highly cost-effective, even with just one-dose of either vaccine. Despite unknown etiology, there is strong field and now economic rationale for administering Hib and PCV during at least one humanitarian emergency. Published by Elsevier Ltd.

  11. A cross-reacting material CRM197 conjugate vaccine induces diphtheria toxin neutralizing antibody response in children and adolescents infected or not with HIV.

    Science.gov (United States)

    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

    2017-07-05

    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.

  12. Initial and subsequent response to pneumococcal polysaccharide and protein-conjugate vaccines administered sequentially to adults who have recovered from pneumococcal pneumonia.

    Science.gov (United States)

    Musher, Daniel M; Rueda, Adriana M; Nahm, Moon H; Graviss, Edward A; Rodriguez-Barradas, Maria C

    2008-10-01

    Controversy persists over the benefits of pneumococcal polysaccharide vaccine (PPV) for adults at high risk for pneumococcal disease. We studied PPV, protein-conjugate pneumococcal vaccine (PCV), and immunologic "priming" with PCV followed by "boosting" with PPV in adults who had recovered from pneumococcal pneumonia. Subjects received PPV followed by PCV 6 months later, or vice versa. The levels of IgG to capsular polysaccharide and opsonophagocytic killing activity (OPK) were studied at baseline and at 4-8 weeks and 6 months after each vaccination. PPV and PCV stimulated similar IgG levels and OPK at 4-8 weeks after vaccination. Six months after receipt of PPV, the antibody levels declined to baseline but remained modestly elevated after receipt of PCV. PCV administered 6 months after PPV stimulated modest increases in IgG level that failed to reach the peaks observed after receipt of PPV. In contrast, PPV administered 6 months after PCV caused dramatic increases in the levels of IgG and OPK for all polysaccharides at 4-8 weeks, consistent with a booster effect. Six months after receipt of the second vaccination, however, levels of IgG and OPK fell precipitously in all patients, approaching baseline levels. In these high-risk subjects who have recovered after treatment for pneumonia, the effect of PPV is short-lived; PCV stimulates a more prolonged response. The use of PPV as a booster following PCV causes early increases in antibody levels, but the level of IgG declines rapidly thereafter, consistent with induction of suppressor cells or tolerance. Protein vaccines may be needed for high-risk adults.

  13. A nationwide study on the impact of pneumococcal conjugate vaccination on antibiotic use and ventilation tube insertion in Denmark 2000-2014.

    Science.gov (United States)

    Howitz, Michael Frantz; Harboe, Zitta Barrella; Ingels, Helene; Valentiner-Branth, Palle; Mølbak, Kåre; Djurhuus, Bjarki Ditlev

    2017-10-13

    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 observational study, comparing trends in the incidence rate of antibiotic prescriptions and VTIs in the period 2000-2014, where PCV7 was introduced in 2007 and PCV13 in 2010. The introduction of PCV7 and PCV13 correlated with changes in the incidence rate from an almost steady increase in prescription of antibiotics in the pre-PCV period to a decreasing incidence for all children age 0-15years. The 2.4 DDD per person year in 2014 was at almost the same level of antibiotic use as in 2000 at 2.3 DDD per person year. Similar patterns were observed in the mostly vaccinated age groups below 5years of age. For VTI we observed a decreasing incidence rate in the years following introduction of PCV13 ending with a slightly higher incidence at 35 per 1000 person years in 2014 compared to 31 in year 2000. We conclude that the steady increase in antibiotic use and VTI in the pre-PCV period have been partially 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. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Antimicrobial resistance among isolates causing invasive pneumococcal disease before and after licensure of heptavalent conjugate pneumococcal vaccine.

    Directory of Open Access Journals (Sweden)

    Tom Theodore Karnezis

    Full Text Available BACKGROUND: The impact of the pneumococcal conjugate vaccine (PCV-7 on antibiotic resistance among pneumococcal strains causing invasive pneumococcal disease (IPD has varied in different locales in the United States. We assessed trends in IPD including trends for IPD caused by penicillin non-susceptible strains before and after licensure of PCV-7 and the impact of the 2008 susceptibility breakpoints for penicillin on the epidemiology of resistance. METHODOLOGY/PRINCIPAL FINDINGS: We performed a retrospective review of IPD cases at Morgan Stanley Children's Hospital of New York-Presbyterian, Columbia University Medical Center. Subjects were < or = 18 years of age with Streptococcus pneumoniae isolated from sterile body sites from January 1995-December 2006. The rate of IPD from 1995-1999 versus 2002-2006 significantly decreased from 4.1 (CI(95 3.4, 4.8 to 1.7 (CI(95 1.3, 2.2 per 1,000 admissions. Using the breakpoints in place during the study period, the proportion of penicillin non-susceptible strains increased from 27% to 49% in the pre- vs. post-PCV-7 era, respectively (p = 0.001, although the rate of IPD caused by non-susceptible strains did not change from 1995-1999 (1.1 per 1,000 admissions, CI(95 0.8, 1.5 when compared with 2002-2006 (0.8 per 1,000 admissions, CI(95 0.6, 1.2. In the multivariate logistic regression model controlling for the effects of age, strains causing IPD in the post-PCV-7 era were significantly more likely to be penicillin non-susceptible compared with strains in the pre-PCV-7 era (OR 2.46, CI(95 1.37, 4.40. However, using the 2008 breakpoints for penicillin, only 8% of strains were non-susceptible in the post-PCV-7 era. CONCLUSIONS/SIGNIFICANCE: To date, there are few reports that document an increase in the relative proportion of penicillin non-susceptible strains of pneumococci causing IPD following the introduction of PCV-7. Active surveillance of pneumococcal serotypes and antibiotic resistance using the new

  15. Do Pneumococcal Conjugate Vaccines Represent Good Value for Money in a Lower-Middle Income Country? A Cost-Utility Analysis in the Philippines.

    Directory of Open Access Journals (Sweden)

    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.

  16. Herd immunity and serotype replacement 4 years after seven-valent pneumococcal conjugate vaccination in England and Wales: an observational cohort study.

    Science.gov (United States)

    Miller, Elizabeth; Andrews, Nicholas J; Waight, Pauline A; Slack, Mary Pe; George, Robert C

    2011-10-01

    The seven-valent pneumococcal conjugate vaccine (PCV7) has reduced vaccine-type (VT) invasive pneumococcal disease but increases in non-vaccine-type (NVT) disease have varied between countries. We assess the effect of the PCV7 vaccination on VT and NVT disease in England and Wales. The study cohort was the population of England and Wales from July, 2000, to June, 2010. We calculated incidence rate ratios (IRRs) to compare incidences of VT and NVT disease before (2000-06) and after (2009-10) the introduction of PCV7. We used data from the national surveillance database. Cases included in our analysis were restricted to those confirmed by culture linked with isolates referred for serotyping at the national reference centre by laboratories in England and Wales. We adjusted for potential bias from missing data (serotype and age of patient) and changes in case ascertainment rates during the study period. 5809 cases of invasive pneumococcal disease were reported in 2009-10, giving an incidence of 10·6 per 100,000 population in 2009-10, which, when compared with the adjusted average annual incidence of 16·1 in 2000-06, gives an overall reduction of 34% (95% CI 28-39). VT disease decreased in all age groups, with reductions of 98% in individuals younger than 2 years and 81% in those aged 65 years or older. NVT disease increased by 68% in individuals younger than 2 years and 48% in those aged 65 years or older, giving an overall reduction in invasive pneumococcal disease of 56% in those younger than 2 years and 19% in those aged 65 years or older. After vaccine introduction, more NVT serotypes increased in frequency than decreased, which is consistent with vaccine-induced replacement. Key serotypes showing replacement were 7F, 19A, and 22F. Increases in NVT invasive pneumococcal disease were not associated with antimicrobial resistance. Despite much serotype replacement, a substantial reduction in invasive pneumococcal disease in young children can be achieved with PCV7

  17. 10-valent pneumococcal non-typeable Haemophilus influenzae protein-D conjugate vaccine (PHiD-CV) induces memory B cell responses in healthy Kenyan toddlers.

    Science.gov (United States)

    Muema, D M; Nduati, E W; Uyoga, M; Bashraheil, M; Scott, J A G; Hammitt, L L; Urban, B C

    2015-08-01

    Memory B cells are long-lived and could contribute to persistence of humoral immunity by maintaining the plasma-cell pool or making recall responses upon re-exposure to an antigen. We determined the ability of a pneumococcal conjugate vaccine to induce anti-pneumococcal memory B cells. Frequencies of memory B cells against pneumococcal capsular polysaccharides from serotypes 1, 6B, 14, 19F and 23F were determined by cultured B cell enzyme-linked immunospot (ELISPOT) in 35 children aged 12-23 months who received pneumococcal non-typeable Haemophilus influenzae protein-D conjugate vaccine (PHiD-CV). The relationships between plasma antibodies and memory B cell frequencies were also assessed. After two doses of PHiD-CV, the proportion of subjects with detectable memory B cells against pneumococcal capsular polysaccharides increased significantly for serotypes 1 (3-45%; P memory B cells were weak. Carriage of serotype 19F at enrolment was associated with poor memory B cell responses against this serotype at subsequent time-points (day 30: non-carriers, 82% versus carriers, 0%, P memory B cells against some of the component pneumococcal capsular polysaccharides. © 2015 British Society for Immunology.

  18. Immunogenicity and safety of human papillomavirus-16/18 AS04-adjuvanted vaccine coadministered with tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine and/or meningococcal conjugate vaccine to healthy girls 11 to 18 years of age: results from a randomized open trial.

    Science.gov (United States)

    Wheeler, Cosette M; Harvey, Bryan M; Pichichero, Michael E; Simon, Michael W; Combs, Stephen P; Blatter, Mark M; Marshall, Gary S; Catteau, Grégory; Dobbelaere, Kurt; Descamps, Dominique; Dubin, Gary; Schuind, Anne

    2011-12-01

    A combined immunization strategy for administration of human papillomavirus (HPV) vaccine with other routine vaccines may lead to better compliance. Reactions and immunologic interference with concomitantly administered vaccines are unpredictable, necessitating clinical evaluation. This was a randomized, open study conducted at 48 centers in the United States (NCT00369824). Healthy girls 11 to 18 years of age were randomized equally to 1 of 6 groups to receive 3 doses of HPV-16/18 AS04-adjuvanted vaccine administered at 0, 1, and 6 or 1, 2, and 7 months, with or without 1 dose of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap) and/or 1 dose of meningococcal polysaccharide diphtheria toxoid conjugate vaccine (MCV4) in different coadministration regimens (1283 girls vaccinated). Coadministered vaccines were injected at separate sites. Antibodies were measured for all vaccine components. Reactogenicity and safety were monitored. The prespecified criteria for noninferiority were met for all primary and secondary immunogenicity end points, demonstrating similar immunogenicity of Tdap and MCV4 when given alone or coadministered with the HPV vaccine. Immunogenicity of the HPV vaccine (in terms of seroconversion rates and geometric mean antibody titers to HPV antigens) was similar, regardless of whether it was given alone or coadministered with Tdap and/or MCV4. No differences were observed in the reactogenicity profile of the HPV vaccine administered alone or coadministered with either Tdap and/or MCV4 in different regimens. Concomitant administration of HPV-16/18 AS04-adjuvanted vaccine with Tdap and/or MCV4 in different regimens did not interfere with the immune response to any of the vaccines and had an acceptable safety profile.

  19. Synthesis, characterization and immunological properties of LPS-based conjugate vaccine composed of O-polysaccharide from pseudomonas aeruginosa IATS 10 bound to recombinant exoprotein A

    International Nuclear Information System (INIS)

    Abu-baker, N. F.; Masoud, H. A.; Jaber, B. M.

    2008-01-01

    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).

  20. Plasma and memory B-cell kinetics in infants following a primary schedule of CRM 197-conjugated serogroup C meningococcal polysaccharide vaccine.

    Science.gov (United States)

    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

    2009-05-01

    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.

  1. Pediatric bacterial meningitis in Japan, 2013-2015 - 3-5 years after the wide use of Haemophilus influenzae type b and Streptococcus pneumoniae conjugated vaccines.

    Science.gov (United States)

    Shinjoh, Masayoshi; Yamaguchi, Yoshio; Iwata, Satoshi

    2017-07-01

    Haemophilus influenzae type b (Hib) vaccine and pneumococcal conjugated vaccine (PCV) have been widely used since 2010 in Japan when both vaccines were supported by the regional governments, and they were covered as routine recommended vaccines in 2013. The incidence of bacterial meningitis due to these organisms decreased in 2011 and 2012, but meningitis due to Streptococcus agalactiae and Escherichia coli remained unchanged. We planned to confirm whether the incidence also decreased in subsequent years. We analyzed the epidemiological and clinical data for 2013-2015, and compared the information obtained in the previous nationwide survey database and our previous reports. We also investigated the risk factors for disease outcome. In the 2013-2015 surveys, 407 patients from 366 hospitals from all prefectures were evaluated. S. agalactiae (33%), Streptococcus pneumoniae (25%), and E. coli (10%) were the main organisms. The total number of patients hospitalized with bacterial meningitis per 1000 admissions decreased from 1.19 in 2009-2010 to 0.37 in 2013-2015 (p influenzae and S. pneumoniae meningitis significantly decreased from 0.66 in 2009-2010 to 0.01 in 2013-2015, and from 0.30 to 0.09, respectively (p influenzae, S. pneumoniae, S. agalactiae, and E. coli in 2013-2015 were 0.0, 4.1, 3.1, and 2.6%, respectively. Risk factors for death and sequelae were consciousness disturbance, convulsion, low CSF glucose, and Staphylococcus sp. as a causative organism (p < 0.01). Hib vaccine and PCV have decreased the rate of bacterial meningitis. S. agalactiae has subsequently become the most common cause of bacterial meningitis in Japan. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  2. Changes in the incidence of pneumonia, bacterial meningitis, and infant mortality 5 years following introduction of the 13-valent pneumococcal conjugate vaccine in a "3+0" schedule.

    Science.gov (United States)

    Becker-Dreps, Sylvia; Blette, Bryan; Briceño, Rafaela; Alemán, Jorge; Hudgens, Michael G; Moreno, Gilberto; Ordoñez, Ana; Rocha, Julio; Weber, David J; Amaya, Erick

    2017-01-01

    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.

  3. Changes in the incidence of pneumonia, bacterial meningitis, and infant mortality 5 years following introduction of the 13-valent pneumococcal conjugate vaccine in a "3+0" schedule.

    Directory of Open Access Journals (Sweden)

    Sylvia Becker-Dreps

    Full Text Available 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

  4. Immunization with the conjugate vaccine Vi-CRM₁₉₇ against Salmonella typhi induces Vi-specific mucosal and systemic immune responses in mice.

    Science.gov (United States)

    Fiorino, Fabio; Ciabattini, Annalisa; Rondini, Simona; Pozzi, Gianni; Martin, Laura B; Medaglini, Donata

    2012-09-21

    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.

  5. Recent trends in pediatric bacterial meningitis in Japan--a country where Haemophilus influenzae type b and Streptococcus pneumoniae conjugated vaccines have just been introduced.

    Science.gov (United States)

    Shinjoh, Masayoshi; Iwata, Satoshi; Yagihashi, Tatsuhiko; Sato, Yoshitake; Akita, Hironobu; Takahashi, Takao; Sunakawa, Keisuke

    2014-08-01

    To investigate the trends in incidence and the characteristics of bacterial meningitis in Japan where Haemophilus influenzae type b (Hib) vaccine and 7-valent pneumococcal conjugated vaccine (PCV7) were introduced in 2008 and 2010, respectively, which was 5-20 years after their introduction in western countries. The nationwide Japanese survey of pediatric and neonatal bacterial meningitis was performed in 2011 and 2012. We analyzed the epidemiological and clinical data, and compared the information obtained in the previous nationwide survey database. We also investigated the risk factors for disease outcome. In the 2011-2012 surveys, 357 patients were evaluated. H. influenzae, Streptococcus pneumoniae, Streptococcus agalactiae and Escherichia coli were the main organisms. The number of patients hospitalized with bacterial meningitis per 1000 admissions decreased from 1.31 in 2009 to 0.43 in 2012 (p meningitis also decreased from 0.66 to 0.08 (p bacterial meningitis. Earlier introduction of these vaccines may have prevented bacterial meningitis among Japanese children. Copyright © 2014 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  6. Biological and Epidemiological Features of Antibiotic-Resistant Streptococcus pneumoniae in Pre- and Post-Conjugate Vaccine Eras: a United States Perspective

    Science.gov (United States)

    Kim, Lindsay; McGee, Lesley; Tomczyk, Sara

    2016-01-01

    SUMMARY Streptococcus pneumoniae inflicts a huge disease burden as the leading cause of community-acquired pneumonia and meningitis. Soon after mainstream antibiotic usage, multiresistant pneumococcal clones emerged and disseminated worldwide. Resistant clones are generated through adaptation to antibiotic pressures imposed while naturally residing within the human upper respiratory tract. Here, a huge array of related commensal streptococcal strains transfers core genomic and accessory resistance determinants to the highly transformable pneumococcus. β-Lactam resistance is the hallmark of pneumococcal adaptability, requiring multiple independent recombination events that are traceable to nonpneumococcal origins and stably perpetuated in multiresistant clonal complexes. Pneumococcal strains with elevated MICs of β-lactams are most often resistant to additional antibiotics. Basic underlying mechanisms of most pneumococcal resistances have been identified, although new insights that increase our understanding are continually provided. Although all pneumococcal infections can be successfully treated with antibiotics, the available choices are limited for some strains. Invasive pneumococcal disease data compiled during 1998 to 2013 through the population-based Active Bacterial Core surveillance program (U.S. population base of 30,600,000) demonstrate that targeting prevalent capsular serotypes with conjugate vaccines (7-valent and 13-valent vaccines implemented in 2000 and 2010, respectively) is extremely effective in reducing resistant infections. Nonetheless, resistant non-vaccine-serotype clones continue to emerge and expand. PMID:27076637

  7. 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.

    Science.gov (United States)

    Togashi, Takehiro; Mitsuya, Nodoka; Kogawara, Osamu; Sumino, Shuji; Takanami, Yohei; Sugizaki, Kayoko

    2016-08-31

    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

  8. Invasive pneumococcal disease in Danish children, 1996-2007, prior to the introduction of heptavalent pneumococcal conjugate vaccine

    DEFF Research Database (Denmark)

    Winther, Thilde N; Kristensen, Tim D; Kaltoft, Margit S

    2008-01-01

    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

  9. Impacto da vacina conjugada contra Streptococcus pneumoniae em doenças invasivas Impact of pneumococcal conjugate vaccine on the prevention of invasive pneumococcal diseases

    Directory of Open Access Journals (Sweden)

    Lucia Ferro Bricks

    2006-07-01

    Full Text Available OBJETIVOS: Rever os estudos que avaliam o impacto da vacina conjugada 7-valente na incidência de doenças invasivas por pneumococo e analisar o possível impacto dessa vacina no Brasil. FONTE DE DADOS:Foram pesquisadas as bases de dados MEDLINE, LILACS, Cochrane Database Reviews (janeiro de 2000 a janeiro de 2006, selecionando-se para análise os artigos contendo as seguintes palavras-chave: Streptococcus pneumoniae, pneumococo, vacina conjugada, resistência, antibióticos e meningite. Também foi realizada busca de informações sobre o tema nos sites do Centers for Disease Control, Ministério da Saúde e Centro de Vigilância Epidemiológica do Estado de São Paulo. SÍNTESE DOS DADOS: A vacina conjugada 7-valente reduziu a incidência de doenças invasivas por pneumococo, número de consultas por doenças respiratórias de vias aéreas superiores e inferiores, consumo de antibióticos e incidência de doenças invasivas por pneumococo por cepas resistentes a antibióticos não apenas nas crianças vacinadas, como em adultos e idosos. No Brasil, os coeficientes de incidência de doenças invasivas por pneumococo em crianças menores de 5 anos são elevados, a taxa de letalidade de meningites pneumocócicas é alta e as taxas de resistência parcial e plena à penicilina aumentaram substancialmente nos últimos 5 anos. CONCLUSÕES:Devido aos benefícios diretos e indiretos do uso em larga escala da vacina conjugada 7-valente, essa vacina deve ser incluída no calendário básico de imunização do Brasil.OBJECTIVES: To evaluate the impact of heptavalent pneumococcal conjugate vaccine in invasive pneumococcal diseases in the United States, and to analyze the potential impact of this vaccine in Brazil. SOURCES OF DATA: MEDLINE, LILACS, Cochrane Database Reviews, as well as the websites of the Centers for Disease Control and Prevention (CDC, Brazilian Ministry of Health and Centro de Vigilância Epidemiológica do Estado de São Paulo from

  10. Salivary antibody levels in adolescents in response to a meningococcal serogroup C conjugate booster vaccination nine years after priming : systemically induced local immunity and saliva as potential surveillance tool

    NARCIS (Netherlands)

    Stoof, Susanne P; van der Klis, Fiona R M; van Rooijen, Debbie M; Bogaert, Debby|info:eu-repo/dai/nl/264105834; Trzcinski, Krzysztof|info:eu-repo/dai/nl/323349609; Sanders, Elisabeth A M|info:eu-repo/dai/nl/126771960; Berbers, Guy A M

    2015-01-01

    BACKGROUND: In several countries large-scale immunization of children and young adults with Meningococcal serogroup C (MenC) conjugate vaccines has induced long-standing herd protection. Salivary antibodies may play an important role in mucosal protection against meningococcal acquisition and

  11. Impact of ten-valent pneumococcal conjugate vaccine on pneumonia in Finnish children in a nation-wide population-based study.

    Directory of Open Access Journals (Sweden)

    Arto A Palmu

    Full Text Available The ten-valent pneumococcal conjugate vaccine (PCV10 was introduced into the Finnish National Vaccination Program (NVP in September 2010 using a 2+1 schedule (3, 5, 12 months. We estimated the direct and indirect effects of PCV10 on pneumonia among children to evaluate the public health impact of the vaccine.We conducted a nation-wide population-based, observational study comparing rates of pneumonia in children before and after the NVP introduction. For the total (direct and indirect effect, the cohort of vaccine-eligible children (born June 1, 2010 or later was followed until the end of 2013 (age range 3-42 months. For the indirect effect, a cohort of older children (age range 7-71 months not eligible for the PCV vaccination was followed from 2011 to 2013. Both cohorts were compared with two season- and age-matched reference cohorts before NVP introduction. Hospitals' in- and outpatient discharge notifications with ICD-10 diagnoses compatible with pneumonia (J10.0, J11.0, J12-J18, J85.1 or J86 as set by the hospital pediatricians were collected from the national Care Register. The main outcome was hospital-treated primary pneumonia (HTPP, defined as primary diagnosis of pneumonia after in-patient hospitalization. We compared rates of pneumonia in the NVP target and reference cohorts by using Poisson regression models.The rate of HTPP episodes was 5.3/1000 person-years in the combined reference cohorts and 4.1/1000 person-years in the target cohort vaccine-eligible children. Compared with the reference cohort, the relative rate reduction in target cohort was 23% (95%CI 18-28 and the absolute reduction 1.3/1000 person-years. In the indirect effect evaluation, we observed continued increase in HTPP incidence until 2011 with a subsequent reduction of 18% (95%CI 10-25 during years 2012 to 2013. Number of empyema diagnoses remained low.A substantial decrease in pneumonia rates was observed both among vaccine-eligible children and among older

  12. Immunogenicity and safety of a 13-valent pneumococcal conjugate vaccine administered to older infants and children naïve to pneumococcal vaccination.

    Science.gov (United States)

    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

    2015-03-30

    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.

  13. Meeting the challenge: prevention of pneumococcal disease with conjugate vaccines Al encuentro del reto: prevención de la enfermedad neumocócica con vacunas conjugadas

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    Irma Gabriela Echániz-Avilés

    2001-08-01

    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

  14. Tetanus Toxoid carrier protein induced T-helper cell responses upon vaccination of middle-aged adults.

    Science.gov (United States)

    van der Heiden, Marieke; Duizendstra, Aafke; Berbers, Guy A M; Boots, Annemieke M H; Buisman, Anne-Marie

    2017-10-09

    Vaccines frequently induce suboptimal immune responses in the elderly, due to immunological ageing. Timely vaccination may be a strategy to overcome this problem, which classifies middle-aged adults asan interesting target group for future vaccine interventions. However, the immunological fitness of the middle-aged population is ill-defined. It is currently unknown whether effective T-cell help towards B-cells is initiated by conjugate-carrier vaccines at middle-age. We characterized systemic Tetanus Toxoid (TT) specific T-helper cell responses in the circulation of middle-aged adults (50-65years of age, n=31) having received the MenACWY-TT vaccination. Blood samples were taken pre- as well as 7days, 28days, and 1year post-vaccination. TT-specific T-cell responses were determined by IFNγ Elispot and by the secretion of IFNγ, IL13, IL10, IL17, and IL21 in cell culture supernatants. Circulating CD4+CXCR5+ICOS+IL21+ cells were analyzed by flow cytometry, and meningococcal and TT-specific IgG responses by bead-based immunoassays. The correlation between the T-cell help and humoral responses was evaluated. Vaccination with a TT-carrier protein induced a mixed TT-specific Th1 (IFNγ), Th2 (IL13, IL10), and Th17 (IL17) response in most participants. Additionally, circulating CD4+CXCR5+ICOS+IL21+ cells were significantly increased 7days post-vaccination. Pre-vaccination TT-specific cytokine production and post-vaccination Th2 responses correlated positively with the increase of CD4+CXCR5+ICOS+IL21+ cells. No correlation between T-cell help and antibody responses was found. The characteristics of the T-cell response upon a TT-carrier vaccination suggests effective T-cell help towards B-cells in response to meningococcal polysaccharides, although the absence of a correlation with the antibody responses warrants further clarification. However, the robust T-helper cell response in middle-aged adults, decades after previous TT vaccinations, strengthens the classification of

  15. Impact of 10-valent pneumococcal conjugate vaccine on pneumococcal meningitis in children up to two years of age in Brazil

    OpenAIRE

    Grando, Indianara Maria; Moraes, Camile de; Flannery, Brendan; Ramalho, Walter Massa; Horta, Marco Aurélio P.; Pinho, Diana Lucia Moura; Nascimento, Gilmara Lima

    2015-01-01

    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 r...

  16. Development and use of a serum bactericidal assay using pooled human complement to assess responses to a meningococcal group A conjugate vaccine in African toddlers.

    Science.gov (United States)

    Bash, Margaret C; Lynn, Freyja; Mocca, Brian; Borrow, Ray; Findlow, Helen; Hassan-King, Musa; Preziosi, Marie-Pierre; Idoko, Olubukola; Sow, Samba; Kulkarni, Prasad; Laforce, F Marc

    2014-05-01

    A meningococcal group A polysaccharide (PS) conjugate vaccine (PsA-TT) has been developed for African countries affected by epidemic meningitis caused by Neisseria meningitidis. Complement-mediated serum bactericidal antibody (SBA) assays are used to assess protective immune responses to meningococcal vaccination. Human complement (hC') was used in early studies demonstrating antibody-mediated protection against disease, but it is difficult to obtain and standardize. We developed and evaluated a method for sourcing hC' and then used the SBA assay with hC' (hSBA) to measure bactericidal responses to PsA-TT vaccination in 12- to 23-month-old African children. Sera with active complement from 100 unvaccinated blood donors were tested for intrinsic bactericidal activity, SBA titer using rabbit complement (rSBA), and anti-group A PS antibody concentration. Performance criteria and pooling strategies were examined and then verified by comparisons of three independently prepared hC' lots in two laboratories. hSBA titers of clinical trial sera were then determined using this complement sourcing method. Two different functional antibody tests were necessary for screening hC'. hSBA titers determined using three independent lots of pooled hC' were within expected assay variation among lots and between laboratories. In African toddlers, PsA-TT elicited higher hSBA titers than meningococcal polysaccharide or Hib vaccines. PsA-TT immunization or PS challenge of PsA-TT-primed subjects resulted in vigorous hSBA memory responses, and titers persisted in boosted groups for over a year. Quantifying SBA using pooled hC' is feasible and showed that PsA-TT was highly immunogenic in African toddlers.

  17. Impact of Haemophilus influenzae Type B Conjugate Vaccines on Nasopharyngeal Carriage in HIV-infected Children and Their Parents From West Bengal, India.

    Science.gov (United States)

    Arya, Bikas K; Bhattacharya, Sangeeta Das; Sutcliffe, Catherine G; Kumar Niyogi, Swapan; Bhattacharyya, Subhasish; Hemram, Sunil; Moss, William J; Panda, Samiran; Saurav Das, Ranjan; Mandal, Sutapa; Robert, Dennis; Ray, Pampa

    2016-11-01

    In addition to reducing Haemophilus influenzae type b (Hib) disease in vaccinated individuals, the Hib conjugate vaccine (HibCV) has indirect effects; it reduces Hib disease in unvaccinated individuals by decreasing carriage. Human immunodeficiency virus (HIV)-infected children are at increased risk for Hib disease and live in families where multiple members may have HIV. The aim of this study is to look at the impact of 2 doses of the HibCV on nasopharyngeal carriage of Hib in HIV-infected Indian children (2-15 years) and the indirect impact on carriage in their parents. This prospective cohort study was conducted in HIV-infected and HIV-uninfected families. Nasopharyngeal swabs were collected from children and parents before and after vaccination. HIV-infected children 2-15 years of age got two doses of HibCV and were followed up for 20 months. Uninfected children 2-5 years of age got 1 dose of HibCV as catch-up. 123 HIV-infected and 44 HIV-uninfected children participated. Baseline colonization in HIV-infected children was 13.8% and dropped to 1.8% (P = 0.002) at 20 months. Baseline carriage in HIV-uninfected children was 4.5% and dropped to 2.3% after vaccination (P = 0.3). HIV-infected parents had 12.3 times increased risk of Hib carriage if their child was colonized (P = 0.04) and had 9.3 times increased risk if their child had persistent colonization postvaccine (P = 0.05). No parent of HIV-uninfected children had Hib colonization at any point. Pneumococcal colonization was associated with increased Hib colonization. Making the HibCV available to HIV-infected children could interrupt Hib carriage in high-risk families.

  18. An open-label randomized clinical trial of prophylactic paracetamol coadministered with 7-valent pneumococcal conjugate vaccine and hexavalent diphtheria toxoid, tetanus toxoid, 3-component acellular pertussis, hepatitis B, inactivated poliovirus, and Haemophilus influenzae type b vaccine.

    Science.gov (United States)

    Rose, Markus A; Juergens, Christine; Schmoele-Thoma, Beate; Gruber, William C; Baker, Sherryl; Zielen, Stefan

    2013-06-21

    In two clinical trials, low-grade fever was observed more frequently after coadministration than after separate administration of two recommended routine pediatric vaccines. Since fever is an important issue with vaccine tolerability, we performed this open-label study on the efficacy and safety of prophylactic use of paracetamol (acetaminophen, Benuron®) in children administered routine 7-valent pneumococcal conjugate vaccine (PCV-7) coadministered with hexavalent vaccine (diphtheria-tetanus-acellular pertussis-hepatitis B, poliovirus, Haemophilus influenzae type b vaccine [DTPa-HBV-IPV/Hib]) in Germany. Healthy infants (N = 301) who received a 3-dose infant series of PCV-7 and DTPa-HBV-IPV/Hib plus a toddler dose were randomly assigned 1:1 to prophylactic paracetamol (125 mg or 250 mg suppositories, based on body weight) at vaccination, and at 6-8 hour intervals thereafter, or a control group that received no paracetamol. Rectal temperature and local and other systemic reactions were measured for 4 days post vaccination; adverse events were collected throughout the study. In the intent-to-treat population, paracetamol reduced the incidence of fever ≥38°C, but this reduction was only significant for the infant series, with computed efficacy of 43.0% (95% confidence interval [CI]: 17.4, 61.2), and not significant after the toddler dose (efficacy 15.9%; 95% CI: -19.9, 41.3); results were similar in the per protocol (PP) population. Fever >39°C was rare during the infant series, such that there were too few cases for assessment. After the toddler dose, paracetamol effectively reduced fever >39°C, reaching statistical significance in the PP population only (efficacy 79%; 95% CI: 3.9, 97.7). Paracetamol also reduced reactogenicity, but there were few significant differences between groups after any dose. No vaccine-related serious adverse events were reported. Paracetamol effectively prevented fever and other reactions, mainly during the infant series

  19. Predictors to parental knowledge about childhood immunisation/EPI vaccines in two health districts in Cameroon prior to the introduction of 13-valent Pneumococcal Conjugate Vaccines (PCV-13)

    Science.gov (United States)

    Libwea, John Njuma; Kobela, Marie; Ollgren, Jukka; Emah, Irene; Tchio, Robert; Nohynek, Hanna

    2014-01-01

    Introduction Pneumonia is vaccine-preventable, but the increasing death toll resulting from the disease in Sub-Saharan Africa is alarming. Several factors account for vaccine failing to reach every child, besides incomplete vaccine coverage. Most of these include the perceptions of parents/guardians and healthcare providers. Previous studies on the introduction of new vaccines have focused on experimental trials, coverage figures and vaccine efficacy in developed countries. Little is known on the factors which may hinder the implementation process despite the huge challenges this may encounter in developing countries. This study described the knowledge, attitude and practices (KAP) of parents/guardians on pneumonia and immunisations/EPI vaccines; identify predictive parental socio-economic/demographic characteristics that of good knowledge on pneumonia infections, routine EPI vaccines and the PCV-13. Finally, the study described health center personnel perceptions about immunisations. Methods The WHO's immunisation coverage cluster survey design was used, involving parents/guardians (n = 205) of children aged 0-59 months and health centre personnel (n = 13) directly concerned with vaccination activities between July-September 2010 in two health districts in Yaounde, Cameroon. Descriptive statistics and multivariate logistic models were used to analyse the parental/guardian data while the health personnel data was only analysed descriptively using SPSS version 17.0. Results Only 19% of the parents/guardians were aware of the availability of the PCV-13. Logistic modelling identified important associations between parental socio-economic/demographic factors and good knowledge on pneumonia disease burden and prevention. Conclusion According to parents/guardians a short and clear message on the dangers of pneumonia and the need for prevention provided to parents/guardians during sensitisation/out-reach campaigns and use of social network avenues would be primordial, if

  20. Vacinas meningocócicas conjugadas: eficácia e novas combinações Meningococcal conjugate vaccines: efficacy and new combinations

    Directory of Open Access Journals (Sweden)

    Marco Aurélio Palazzi Sáfadi

    2006-07-01

    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

  1. Rationale and methods of a randomized controlled trial of immunogenicity, safety and impact on carriage of pneumococcal conjugate and polysaccharide vaccines in infants in Papua New Guinea.

    Science.gov (United States)

    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

    2017-01-01

    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

  2. Three-year antibody persistence and safety after a single dose of combined haemophilus influenzae type b (Hib)-Neisseria meningitidis serogroup C-tetanus toxoid conjugate vaccine in Hib-primed toddlers.

    Science.gov (United States)

    Booy, Robert; Richmond, Peter; Nolan, Terry; McVernon, Jodie; Marshall, Helen; Nissen, Michael; Reynolds, Graham; Ziegler, John B; Stoney, Tanya; Heron, Leon; Lambert, Stephen; Mesaros, Narcisa; Peddiraju, Kavitha; Miller, Jacqueline M

    2013-02-01

    Persistence of seroprotective bactericidal antibody titers is important for long-term protection against meningococcal serogroup C disease in young children. Antibody persistence values were determined in children up to 3 years after vaccination with a single dose of the combined Haemophilus influenzae type b (Hib)-Neisseria meningitidis serogroup C (MenC)-tetanus toxoid (TT) conjugate vaccine (Hib-MenC-TT; www.ClinicalTrials.gov: NCT00326118). The children had been randomized at ages 12-18 months to receive either 1 dose of Hib-MenC-TT (Hib-MenC group) or separately administered Hib-TT conjugate vaccine and MenC-CRM197 (MCC) vaccine (Hib plus MCC group). All children had been primed in infancy with a Hib vaccine. Antibodies against MenC were measured by a serum bactericidal assay using rabbit complement (rSBA-MenC) and antibodies against Hib polyribosylribitol phosphate were assessed by enzyme-linked immunosorbent assay. The rSBA-MenC titers ≥1:8 were demonstrated 3 years after vaccination in 64.2% and 53.2% of participants in the Hib-MenC group and in the Hib plus MCC group, respectively. Antipolyribosylribitol phosphate concentrations ≥0.15 µg/mL persisted in >98% of participants in both groups. The rSBA-MenC geometric mean titers and antipolyribosylribitol phosphate geometric mean concentrations remained higher 3 years after vaccination than before vaccination. No serious adverse events assessed by the investigator as being related to vaccination were reported. In this antibody persistence study of Hib-primed but MenC-naïve toddlers who received a single dose of Hib-MenC-TT, protective antibody levels against Hib and MenC were maintained in the majority of children 3 years after vaccination.

  3. Efficacy of pneumococcal nontypable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV in young Latin American children: A double-blind randomized controlled trial.

    Directory of Open Access Journals (Sweden)

    Miguel W Tregnaghi

    2014-06-01

    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

  4. Adverse events following quadrivalent meningococcal CRM-conjugate vaccine (Menveo®) reported to the Vaccine Adverse Event Reporting system (VAERS), 2010-2015.

    Science.gov (United States)

    Myers, Tanya R; McNeil, Michael M; Ng, Carmen S; Li, Rongxia; Lewis, Paige W; Cano, Maria V

    2017-03-27

    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.

  5. Efficacy of Pneumococcal Nontypable Haemophilus influenzae Protein D Conjugate Vaccine (PHiD-CV) in Young Latin American Children: A Double-Blind Randomized Controlled Trial

    Science.gov (United States)

    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

    2014-01-01

    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

  6. Pharmacoeconomic aspects related to the 13-valent pneumococcal conjugate vaccine: preliminary analysis of the data from the ASL of Viterbo

    Directory of Open Access Journals (Sweden)

    Dari Silvia

    2014-12-01

    Full Text Available INTRODUCTION: Streptococcus pneumoniae is a pathogen of considerable importance to public health because it causes morbidity and mortality on the world population. It has more than 90 serotypes with different epidemiological characteristics and pathogenicity. Some categories of the population are particularly vulnerable to infection. The Regional Plan for the Prevention of Lazio for vaccination, based on the national plan for the prevention for vaccination involves the active offer of vaccination no 13-valent PCV, with a target of at least 90% in children 24 months of age.OBJECTIVE: To begin to assess the real economic impact of disease attributable to Pneumococcus, starting from the analysis of hospital discharge records (SDO of the Viterbo's ASL.METHODS: The model is structured follows the observational approach of 33 months, from January 2012 to September 2014, selecting the SDO with a principal diagnosis of Streptococcus Pneumoniae diseases and those with a principal diagnosis of respiratory diseases without etiological diagnosis, which, with good approximation, it can be considered responsible for Streptococcus pneumoniae 40%.RESULTS: From the preliminary analysis of the data, evaluating only patients diagnosed due to Pneumococcus, is known as the only pediatric cases hospitalized are between 0 and 1 year. Therefore one might assume that vaccination disbursed to the child population with 13-valent PCV, has ensured effective protection to persons of the age group 2-18 years.CONCLUSIONS: The importance of this study is the observation conducted on an ASL, (similar in size and catchment area to many Italian realty of the vaccination coverage effects, as provided by PRPV Lazio Region, on hospitalizations by Pneumococcus. The study offers a moment of reflection for decision makers, as it would be interesting to conduct pharmacoeconomic’s analysis in the presence of vaccination strategies extended to adults, especially for those at risk

  7. Measuring the effects of pneumococcal conjugate vaccine (PCV7) on Streptococcus pneumoniae carriage and antibiotic resistance: the Palestinian-Israeli Collaborative Research (PICR).

    Science.gov (United States)

    Daana, Muhannad; Rahav, Galia; Hamdan, Ayob; Thalji, Amin; Jaar, Fuad; Abdeen, Ziad; Jaber, Hanaa; Goral, Aviva; Huppert, Amit; Raz, Meir; Regev-Yochay, Gili

    2015-02-18

    The Palestinian-Israeli Collaborative Research (PICR) cross-conflict setting provided a unique opportunity to study overall and indirect effects of pneumococcal conjugate vaccine (PCV7), in two closely related Palestinian populations governed by two distinct health authorities with distinct vaccination policies. Here, PCV7 effects on pneumococcal carriage, serotype distribution and antibiotic resistance are reported. Annual cross-sectional surveys of pneumococcal carriage were performed during 2009-2011 among Palestinian children (≤5 years) (a) under Palestinian-Authority (PA) health policy (Ramallah, Nablus and Bethlehem), where PCV7 was unlicensed (b) under Israeli health policy (East-Jerusalem (EJ)) where PCV7 was rapidly implemented from July 2009. Clinical data were collected, pneumococci identified and characterized for antibiotic susceptibilities and serotype. Analyses included multivariate logistic models with an interaction term for PCV7-effect. Altogether, 2755 children from PA (n=1772) and EJ (n=983) were enrolled, of which ~30% were pneumococcal carriers. While overall carriage was not affected by vaccination policy, carriage of vaccine-type (VT7) strains decreased from 52% to 22% (p<0.001) in EJ, where PCV was implemented, but not in PA. This was accompanied by an increase in non-VT13 strains from 34% to 65% (p<0.001) in EJ, but not in PA. Furthermore, within two years post-PCV7 introduction, proportion of multi-drug resistant strains, which was initially 23% in both populations, decreased significantly in EJ, to 10%, while simultaneously it increased in PA to 33% (p<0.001). Similar trends were observed for resistance to most antibiotic groups. The proportion of resistant isolates among non-VT13 strains did not change during the study period. The unique study design distinguishes secular and seasonal effects from true vaccine effects. While PCV7 did not affect overall pneumococcal carriage rate, VT7 strains, many of which were antibiotic resistant

  8. Nasopharyngeal Pneumococcal Colonization and Impact of a Single Dose of 13-Valent Pneumococcal Conjugate Vaccine in Indian Children With HIV and Their Unvaccinated Parents.

    Science.gov (United States)

    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

    2018-05-01

    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.

  9. The changing epidemiology of invasive pneumococcal disease at a tertiary children's hospital through the 7-valent pneumococcal conjugate vaccine era: a case for continuous surveillance.

    Science.gov (United States)

    Ampofo, Krow; Pavia, Andrew T; Chris, Stockmann; Hersh, Adam L; Bender, Jeffrey M; Blaschke, Anne J; Weng, Hsin Yi Cindy; Korgenski, Kent E; Daly, Judy; Mason, Edward O; Byington, Carrie L

    2012-03-01

    In 2000, a 7-valent pneumococcal conjugate vaccine (PCV7) was licensed for use among US children. Many sites have since reported changes in invasive pneumococcal disease (IPD). We recognized an opportunity to describe the changes in epidemiology, clinical syndromes, and serotype distribution during a 14-year period including 4 years before vaccine introduction and spanning the entire PCV7 era. Cases were defined as children <18 years of age who were cared for at Primary Children's Medical Center for culture-confirmed IPD. We defined the prevaccine period as the time frame spanning from 1997 to 2000 and the postvaccine period from 2001 to 2010. Demographics, clinical data, and outcomes were collected through electronic query and chart review. Streptococcus pneumoniae serotyping was performed using the capsular swelling method. The median age of children with IPD increased from 19 months during the prevaccine period to 27 months during postvaccine period (P = 0.02), with a larger proportion of IPD among children older than 5 years. The proportion of IPD associated with pneumonia increased substantially from 29% to 50% (P < 0.001). This increase was primarily attributable to an increase in complicated pneumonia (17% to 33%, P < 0.001). Nonvaccine serotypes 7F, 19A, 22F, and 3 emerged as the dominant serotypes in the postvaccine period. In children with IPD who were younger than 5 years, for whom vaccine is recommended, 67% of the cases were caused by serotypes in 13-valent PCV during 2005 to 2010. After PCV7 was introduced, significant changes in IPD were noted. One-third of IPD occurred in children older than 5 years, who were outside the age-group for which PCV is recommended. Continued surveillance is warranted to identify further evolution of the epidemiology, clinical syndromes, and serotype distribution of S. pneumoniae after 13-valent PCV licensure.

  10. Effectiveness of Seven and Thirteen Valent Pneumococcal Conjugate Vaccines in a Schedule without a Booster dose: a Ten Year Observational Study.

    Science.gov (United States)

    Jayasinghe, Sanjay; Chiu, Clayton; Quinn, Helen; Menzies, Rob; Gilmour, Robin; McIntyre, Peter

    2018-02-17

    Uniquely among high income countries, Australia uses a 3+0 schedule (3 primary doses; no booster) for infant pneumococcal conjugate vaccine since January 2005, initially 7-valent (PCV7) then 13-valent (PCV13) from July 2011. We measured vaccine effectiveness (VE) of both PCVs against invasive pneumococcal disease (IPD) by two methods. Cases were IPD notifications to national surveillance system in children eligible for respective PCVs. For the case-control method, up to ten age-matched controls were derived from Australian Childhood Immunisation Register. For the indirect-cohort method, controls were IPD cases due to serotypes not in PCVs. VE was calculated as (1-odds ratio)x100 by logistic regression. VE waning was estimated as odds ratios of vaccine type (VT) IPD in consecutive 12 month periods post dose three. Between 2005 and 2014, there were 1209 and 308 IPD cases in PCV7-eligible and PCV13-eligible cohorts respectively. Both methods gave comparable VE estimates. In infants, VE for three doses against VT IPD was 92.9% (95%CI 27.7 to 99.3%) for PCV7 and 86.5% (11.7 to 97.9%) for PCV13. PCV13 VE against 19A IPD was 90.0% (95%CI 71.8 to 96.5%). From 12 months post-dose three odd ratio of VT IPD by 24-36 months increased significantly for PCV7 (5.6 95% CI 1.2- 25.4) and PCV13 (5.9 95% CI 1.0-35.2). For both PCVs in a 3+0 schedule, despite similar VE progressive increase in breakthrough cases only occurred post PCV13. This supports the importance of a booster dose of PCV13 in the second year of life to maintain direct protection.

  11. Adolescent meningococcal serogroup A, W and Y immune responses following immunization with quadrivalent meningococcal A, C, W and Y conjugate vaccine : Optimal age for vaccination

    NARCIS (Netherlands)

    van Ravenhorst, Mariëtte B.; van der Klis, Fiona R M; van Rooijen, Debbie M; Sanders, Elisabeth A.M.; Berbers, Guy A M

    2017-01-01

    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

  12. Adolescent meningococcal serogroup A, W and Y immune responses following immunization with quadrivalent meningococcal A, C, W and Y conjugate vaccine: Optimal age for vaccination.

    NARCIS (Netherlands)

    van Ravenhorst, Mariëtte B; van der Klis, Fiona R M; van Rooijen, Debbie M; Sanders, Elisabeth A M; Berbers, Guy A M

    2017-01-01

    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

  13. Effect of the 13-valent pneumococcal conjugate vaccine on invasive pneumococcal disease in England and Wales 4 years after its introduction: an observational cohort study.

    Science.gov (United States)

    Waight, Pauline A; Andrews, Nicholas J; Ladhani, Shamez N; Sheppard, Carmen L; Slack, Mary P E; Miller, Elizabeth

    2015-05-01

    The 13-valent pneumococcal conjugate vaccine (PCV13) protects against key serotypes that increased after routine immunisation with the seven-valent vaccine (PCV7), but its potential for herd protection and serotype replacement is uncertain. The aim of this study was to analyse the effect of the 13-valent pneumococcal conjugate vaccine on invasive pneumococcal disease in England and Wales 4 years after its introduction. We used a national dataset of electronically reported and serotyped invasive pneumococcal disease cases in England and Wales to estimate incidence rate ratios (IRRs) for vaccine and non-vaccine type invasive pneumococcal disease between July, 2013, and June, 2014, versus the pre-PCV13 and pre-PCV7 baseline. Incidence rates were corrected for missing serotype data and changes in surveillance sensitivity over time. An over-dispersed Poisson model was used to estimate IRRs and confidence intervals. Incidence of invasive pneumococcal disease in the epidemiological year 2013/14 decreased by 32% compared with the pre-PCV13 baseline (incidence 10·14 per 100,000 in 2008-10 vs 6·85 per 100,000 in 2013/14; IRR 0·68, 95% CI 0·64-0·72). This was due to an 86% reduction of the serotypes covered by PCV7 (1·46 vs 0·20 per 100,000; IRR 0·14, 0·10-0·18) and a 69% reduction of the additional six serotypes covered by PCV13 (4·48 vs 1·40 per 100,000; IRR 0·31, 0·28-0·35). When compared with the pre-PCV7 baseline, there was a 56% overall reduction in invasive pneumococcal disease (15·63 vs 6·85 per 100,000; IRR 0·44, 95% CI 0·43-0·47). Compared with the pre-PCV13 baseline, the incidence of non-PCV13 serotypes increased (incidence all ages 4·19 vs 5·25 per 100,000; IRR 1·25, 95% CI 1·17-1·35) due to increases across a broad range of serotypes in children younger than 5 years and in people aged 45 years or more. In children younger than 5 years, incidence of non-PCV13 serotypes in 2013/14 was higher than in 2012/13 (age Wales has reduced the

  14. Co-administration of a novel Haemophilus influenzae type b and Neisseria meningitidis serogroups C and Y-tetanus toxoid conjugate vaccine does not interfere with the immune response to antigens contained in infant vaccines routinely used in the United States.

    Science.gov (United States)

    Marshall, Gary S; Marchant, Colin D; Blatter, Mark; Friedland, Leonard R; Aris, Emmanuel; Miller, Jacqueline M

    2011-02-01

    An investigational combined Haemophilus influenzae type b (Hib) and Neisseria meningitidis serogroups C and Y tetanus toxoid conjugate vaccine (HibMenCY-TT) has been developed to protect infants from invasive disease caused by Hib and these meningococcal serogroups without adding injections to the immunization schedule. Incorporation of this novel vaccine into the US vaccination schedule will require demonstration of a lack of immunologic interference with other routine pediatric vaccines. This study assessed the immune response to 7-valent pneumococcal conjugate vaccine (PCV7) and combined diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus vaccine (DTaP-HepB-IPV) when separately co-administered with HibMenCY-TT as compared to a US-licensed H. influenzae type b tetanus toxoid conjugate vaccine (Hib-TT) at 2, 4, 6 (N=606) and 12-15 months of age (N=366). HibMenCY-TT was non-inferior to Hib-TT in terms of antibody responses to all Streptococcus pneumoniae serotypes contained in PCV7 and the diphtheria, tetanus, pertussis, hepatitis B and poliovirus antigens contained in DTaP-HepB-IPV one month after the third vaccine dose, and the anti-tetanus geometric mean antibody concentration (GMC) was significantly higher in the HibMenCY-TT group than in the Hib-TT group. In an exploratory analysis, no significant differences in the proportion of subjects with anti-pneumococcal antibody concentrations ≥0.2 µg/ml or anti-pneumococcal GMC were seen between the two groups after the fourth vaccine dose. A schedule of HibMenCY-TT given concomitantly with PCV7 and DTaP-HepB-IPV would be expected to protect infants against all of the targeted diseases.

  15. Updated postlicensure surveillance of the meningococcal C conjugate vaccine in England and Wales: effectiveness, validation of serological correlates of protection, and modeling predictions of the duration of herd immunity.

    Science.gov (United States)

    Campbell, Helen; Andrews, Nick; Borrow, Ray; Trotter, Caroline; Miller, Elizabeth

    2010-05-01

    Meningococcal serogroup C conjugate (MCC) vaccines were licensed in the United Kingdom more than 10 years ago based on correlates of protection that had previously been established for serogroup C-containing polysaccharide vaccines by using the serum bactericidal antibody (SBA) assay. These correlates of protection were subsequently validated against postlicensure estimates of observed vaccine effectiveness up to 7 to 9 months after the administration of the MCC vaccine. Vaccine effectiveness was, however, shown to fall significantly more than 1 year after the administration of a 3-dose course in infancy. Despite this finding, the marked impact on serogroup C disease has been sustained, with the lowest recorded incidence (0.02 case per 100,000 population) in the 2008-2009 epidemiological year, mainly due to the indirect herd immunity effect of the vaccine in reducing carriage. Updated estimates of vaccine effectiveness through 30 June 2009 confirmed high short-term protection after vaccination in infancy, at 97% (95% confidence interval [CI], 91% to 99%), falling to 68% (95% CI, -63% to 90%) more than a year after vaccination. The observed vaccine effectiveness more than 12 months postvaccination was consistent with measured declining SBA levels, but confidence intervals were imprecise; vaccine effectiveness estimates were consistent with SBA titers of 1:4 or 1:8 as correlates of long-term protection after a primary course in infants. Modeling suggested that protection against carriage persists for at least 3 years and predicted the stabilization of serogroup C disease at low levels (fewer than 50 cases per year) up to 2015-2016.

  16. Determining trace amounts and the origin of formaldehyde impurity in Neisseria meningitidis A/C/Y/W-135-DT conjugate vaccine formulated in isotonic aqueous 1× PBS by improved C18-UPLC method.

    Science.gov (United States)

    Gudlavalleti, Seshu K; Crawford, Erika N; Tran, Nhi N; Orten, Dana J; Harder, Jeffery D; Reddy, Jeeri R

    2015-03-25

    The ability to accurately measure and report trace amounts of residual formaldehyde impurity in a vaccine product is not only critical in the product release but also a regulatory requirement. In many bacterial or viral vaccine manufacturing procedures, formaldehyde is used either at a live culture inactivation step or at a protein de-toxification step or at both. Reported here is a validated and improved C18-UPLC method (developed based on previously published C-8 HPLC method) to determine the traces of formaldehyde process impurity in a liquid form Neisseria meningitidis A/C/Y/W-135-DT conjugate vaccine formulated in isotonic aqueous 1× PBS. UPLC C-18 column and the conditions described distinctly resolved the 2,4-DNPH-HCHO adduct from the un-reacted 2,4-DNPH as detected by TUV detector at 360 nm. This method was shown to be compatible with PBS formulation and extremely sensitive (with a quantitation limit of 0.05 ppm) and aided to determine formaldehyde contamination sources by evaluating the in-process materials as a track-down analysis. Final nanogram levels of formaldehyde in the formulated single dose vialed vaccine mainly originated from the diphtheria toxoid carrier protein used in the production of the conjugate vaccine, whereas relative contribution from polysaccharide API was minimal. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Direct Comparison of Immunogenicity Induced by 10- or 13-Valent Pneumococcal Conjugate Vaccine around the 11-Month Booster in Dutch Infants.

    Directory of Open Access Journals (Sweden)

    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

  18. HIV Infection and the Epidemiology of Invasive Pneumococcal Disease (IPD in South African Adults and Older Children Prior to the Introduction of a Pneumococcal Conjugate Vaccine (PCV.