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Sample records for 7-valent conjugate vaccine

  1. Invasive pneumococcal infection despite 7-valent conjugated vaccine

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    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.

  2. 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

    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...... and cost-effectiveness of vaccination with the 7-valent conjugated pneumococcal vaccine compared with no vaccination, in all infants in Sweden, taking herd immunity into account. A Markov model was used and a hypothetical birth cohort was simulated for a lifelong perspective. The results show...... 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...

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

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    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. Net-indirec

  4. Compared effectiveness of the 7-valent pneumococcal conjugate vaccine in children with the 13-valent vaccine in adults.

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    Gaillat, J

    2013-06-01

    13-valent-pneumococcal conjugated vaccine was recently approved in the USA and Europe for adults 50 years of age or more. But this approval was followed by recommendations limiting its use to immunocompromised and asplenic patients. The extension of indications to adults was based on the well-demonstrated clinical effectiveness in infants less than 2 years of age, and on a better immune response either quantitatively or qualitatively with conjugated vaccines compared to the immunogenicity of plain polysaccharide vaccines. Nevertheless, the issue was to know whether results observed with the 7-valent pneumococcal conjugate vaccine in children are reproducible in adults with the 13-valent. The answer was given by comparing the epidemiological and physiopathological data, and the immunological response of the two populations. Very few clinical effectiveness studies in adults are available. We had for aim to assess these various issues in infants and adults. A lot of questions remain, such as the unknown impact of serotype replacement with the 13-valent pneumococcal conjugated vaccine on the clinical epidemiology and emergent Streptococcus pneumoniae pathogenicity, while waiting for the CAPITA study results expected in 2014.

  5. Economic evaluation of vaccination programme of 7-valent pneumococcal conjugate vaccine to the birth cohort in Japan.

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    Hoshi, Shu-ling; Kondo, Masahide; Okubo, Ichiro

    2012-05-09

    Aiming to introduce 7-valent pneumococcal conjugate vaccine (PVC-7) into routine vaccination schedule, the government of Japan gives a temporary budget to encourage municipalities in launching public vaccination programme which started on November 26, 2010 and ends on March 31, 2012. This study aims to appraise the 'value for money' of PCV-7 vaccination programme from the societal perspective and the budget impact from the perspective of municipalities, which is responsible for providing routine vaccination. We conducted a cost-effectiveness analysis with Markov modelling and calculated incremental cost-effectiveness ratio (ICER) value of launching such programme with two levels of co-payment, ¥1000 (US$13) or ¥0, and two scenarios of the uptake of vaccine (vaccinated-alone or co-vaccinated with other vaccines). We found that when vaccinated-alone, ICERs in QALY were ¥7,441,000 (US$93,013) or ¥9,065,000 (US$113,313), and when co-vaccinated ¥7,441,000 (US$93,013) or ¥5,489,000 (US$68,613), without or with productivity loss, respectively, regardless of co-payment level of the programme. Co-vaccinated programmes had lower ICER than vaccinated-alone programmes due to the savings in productivity loss. By adopting WHO's classification that an intervention is 'cost-effective' if ICER (in QALY) is between 1 and 3 times of GDP as a criterion, PCV-7 vaccination programme in Japan is concluded as "cost-effective" from the perspective of society. The introduction of either no co-payment or ¥1000 (US$13) co-payment vaccination programme appears to be not budget saving for the first 6 years, whereas the level of budget impact are less than ¥11,000,000 (US$137,500) or ¥8,500,000 (US$106,250), respectively, for a municipality with 1000 birth cohort in the 1st year and 2nd to 5th year birth cohort proportional to the birth cohort population of estimated future population.

  6. 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), chro

  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.

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    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. Nasopharyngeal flora in children with acute otitis media before and after implementation of 7 valent pneumococcal conjugate vaccine in France

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    Cohen Robert

    2012-03-01

    Full Text Available Abstract Background Several studies have investigated the impact of 7-valent pneumococcal conjugate vaccine (PCV7 on pneumococcal (Sp and staphylococcal (Sa nasopharyngeal (NP carriage. Few have investigated the impact on Haemophilus influenzae (Hi and Moraxella catarrhalis (Mc carriage. We aimed to compare the NP carriage rates in young children with acute otitis media (AOM before and after PCV7 implementation in France. Methods Prior to PCV7 implementation, we performed 4 successive randomized trials with NP samples. These studies compared several antibiotic regimens for treating AOM in young children (6 to 30 months. After PCV7 implementation, to assess the impact of the vaccination program on NP flora, young children with AOM were enrolled in a prospective surveillance study. In each study, we obtained an NP sample to analyze the carriage rates of Sp, Hi, Mc and Sa and the factors influencing the carriage. Standardized history and physical examination findings were recorded; the methods used for NP swabs (sampling and cultures were the same in all studies. Results We enrolled 4,405 children (mean age 13.9 months, median 12.8. Among the 2,598 children enrolled after PCV7 implementation, 98.3% were vaccinated with PCV7. In comparing the pre- and post-PCV7 periods, we found a slight but non-significant decrease in carriage rates of pneumococcus (AOR = 0.85 [0.69;1.05], H. influenzae (AOR = 0.89 [0.73;1.09] and S. aureus (AOR = 0.92 [0.70;1.19]. By contrast, the carriage rate of M. catarrhalis increased slightly but not significantly between the 2 periods (AOR = 1.08 [0.95;1.2]. Among Sp carriers, the proportion of PCV7 vaccine types decreased from 66.6% to 10.7% (P Conclusion The carriage rates of otopathogen species (Sp, Hi, Mc and Sa did not significantly change in children with AOM after PCV7 implementation in France. However, we observed significant changes in carriage rates of PCV7 vaccine serotypes and penicillin non-susceptible Sp.

  9. Economic evaluation of universal 7-valent pneumococcal conjugate vaccination in Taiwan: A cost-effectiveness analysis

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    David Bin Chia Wu

    2013-03-01

    Conclusion: Taking herd effect and indirect costs into account, PCV7 vaccination is cost-effective in Taiwan. Further pharmacoeconomic model should include herd effect in CEA of infectious disease research.

  10. Effectiveness of the 7-valent pneumococcal conjugate vaccine against vaccine-type invasive disease among children in Uruguay: an evaluation using existing data.

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    Picón, Teresa; Alonso, Lucía; García Gabarrot, Gabriela; Speranza, Noelia; Casas, Mariana; Arrieta, Fernando; Camou, Teresa; Rosa, Raquel; De Oliveira, Lucia Helena; Verani, Jennifer Rabke

    2013-07-02

    The 7-valent pneumococcal conjugate vaccine (PCV7) was introduced into the routine immunization program in Uruguay in March 2008 with a 2-dose primary series (given at 2 and 4 months) plus a booster (at 12 months) and a catch-up campaign (two doses given at 15 and 17 months). We used a case-control methodology and existing laboratory surveillance and immunization registry data from Uruguay to evaluate PCV7 effectiveness against vaccine-type invasive pneumococcal disease (VT-IPD). Cases of VT-IPD (with pneumococcus obtained from a normally sterile site) were identified through the National Reference Laboratory. Age- and neighborhood-matched controls were obtained through a national immunization registry in which all children are enrolled at birth regardless of vaccine receipt; all eligible controls were included. Immunization status of cases and controls was assessed through the immunization registry, and conditional logistic regression was used to calculate PCV7 effectiveness. Between April 2008 and February 2010, 44 cases of VT-IPD among childrenUruguay-a middle-income country using a 2-dose primary series plus a booster dose and a limited catch-up campaign. These data also highlight the utility of surveillance and high-quality immunization registries for evaluating the effectiveness of vaccines.

  11. 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

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    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.

  12. 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

    Science.gov (United States)

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

    2004-09-01

    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.

  13. Cost-Effectiveness and Health Benefits of Pediatric 23-Valent Pneumococcal Polysaccharide Vaccine, 7-Valent and Forecasting 13-Valent Pneumococcal Conjugate Vaccines in China.

    Science.gov (United States)

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

    2016-06-24

    Each year in China, approximately 700,000 children under 5 years old are diagnosed with pneumonia, and 30,000 die from 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 (ICER). Under baseline assumptions, PPV-23 is currently the only cost-effective option, while 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%). ICERs 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 ICERs 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 benefits, the replacement of PCV-7 with PCV-13 should be

  14. 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.

  15. [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.

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

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    Rivera-Olivero, Ismar A; Del Nogal, Berenice; Fuentes, Mariana; Cortez, Rossana; Bogaert, Debby; Hermans, Peter W M; Waard, Jacobus H de

    2014-06-30

    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). 82 children (age 2-59 months) with sickle cell anemia (n=22), chronic heart disease (n=19), HIV infection (n=12), immune-suppressive therapy (n=11) and other IPD-predisposing conditions (n=18) were vaccinated with PCV7 according to CDC-recommended age-related immunization schedules. Blood samples were taken to determine the concentration of IgG antibody, and nasopharyngeal swabs were obtained to isolate Streptococcus pneumoniae, before the first vaccine dose and 1 month after completion of the vaccination schedule. Pneumococcal carriage prior to the first immunization was 27% (n=22), with the most frequently carried serotypes being vaccine serotypes 6B (22%) and 14 (13%). One month after completion of the vaccination scheme pneumococcal carriage was 22% (n=17), dominated by non-vaccine serotypes 19A (24%) and 7F (12%). Before immunization, 65% of the subjects had IgG antibody titers >0.35 μg/mL for five serotypes tested. Post-vaccination, 100% of the subjects showed titers >1.0 μg/mL for all PCV7 serotypes with geometric mean concentrations (GMC) ranging from 1.75 μg/mL (serotype 23F) to 17.16 μg/mL (serotype 14). Children previously colonized with serotype 6B had a significantly lower GMC to this serotype following immunization than children not carrying 6B prior to the first PCV dose (p<0.05). PCV7 is highly immunogenic in Venezuelan children at high-risk for IPD. Vaccination was associated with an immediate shift in nasopharyngeal carriage toward non-PCV7 serotypes. Finally, we observed serotype-specific hyporesponsiveness to immunization after natural carriage with the same serotype in high-risk children. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. 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 non

  18. 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

  19. Serotype and clonal evolution of penicillin-nonsusceptible invasive Streptococcus pneumoniae in the 7-valent pneumococcal conjugate vaccine era in Italy.

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    Gherardi, Giovanni; D'Ambrosio, Fabio; Visaggio, Daniela; Dicuonzo, Giordano; Del Grosso, Maria; Pantosti, Annalisa

    2012-09-01

    The percentage of invasive penicillin-nonsusceptible pneumococci (PNSSP) isolated in Italy in the seven-valent pneumococcal conjugate vaccine (PCV7) era moderately increased in comparison to the pre-PCV7 era. Increase of nonvaccine serotypes was observed among PNSSP. The most frequent PNSSP clones were the same as those identified in the pre-PCV7 era, although they were present in different proportions. Clonal expansion, emergence of new clones, and acquisition of penicillin resistance by established clones contributed to the maintenance of penicillin resistance.

  20. Ecomomic Evaluation of 7-Valent Pneumococcal Conjugate Vaccine(PCV7)%儿童七价肺炎球菌结合疫苗的成本效果分析

    Institute of Scientific and Technical Information of China (English)

    朱琳; 刘国恩; 李冬美; 程迪尔; 董鹏

    2013-01-01

      目的:基于支付方角度,就七价肺炎球菌结合疫苗(PCV7)纳入深圳市城市免疫规划(City Immunization Program, CIP)与否两种情况,对2岁以下儿童注射疫苗在全人群获得的免疫效果和成本效果进行实证研究。方法:疾病负担数据取自深圳市三甲医院2010年肺炎链球菌性疾病患者的电子病历;流行病学病学数据来自台湾健保局肺炎链球菌性疾病法定上报系统;疫苗效果数据来自国内外公开发表的临床试验文献;最后根据接种方案及结果构建的决策树模型和深圳市人口学数据模拟运算,评估实施接种政策后的免疫效果和成本效果。结果:当PCV7未纳入深圳CIP作为二类疫苗使用时,由于较低的接种率和较高的接种价格,结果不具备成本效果优势;当PCV7纳入深圳CIP作为一类疫苗使用时,预测CIP的3+1接种策略每年共可预防36594人患肺炎链球菌性脑膜炎、肺炎链球菌性菌血症、全因肺炎和全因中耳炎,并可避免162人死亡,共获得2223个生命年和2004个质量调整生命年,平均每获得一个质量调整生命年的成本为11.8万元。结论: PCV7纳入深圳CIP后,能大幅降低儿童及成人肺炎球菌相关疾病及死亡。根据WHO对药物经济学评价的推荐意见,其介于我国1倍至3倍的人均GDP 间,认为具有成本效果优势。%Objective: To evaluate the potential clinical and economic benefits of introducing a public financed City Immunization Program (CIP) to pay for the 7-valent pneumococcal conjugate vaccine (PCV7). Methods: Disease burden data was gained from the patients’electronic record of streptococcus pneumoniae disease in tertiary hospital in 2010. Epidemic disease data was obtained from Taiwan National Health Insurance legal reportiog systerm of streptococcus pneumociae was taken from the preliminary results summarized at home and abroad. The Vaccine efficacy for PCV7

  1. Immunogenicity and safety study of a new DTaP-IPV-Hep B-PRP-T combined vaccine compared to a licensed DTaP-IPV-Hep B//PRP-T comparator, both concomitantly administered with a 7-valent pneumococcal conjugate vaccine at 2, 4, and 6 months of age in Thai infants.

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    Kosalaraksa, Pope; Thisyakorn, Usa; Benjaponpitak, Suwat; Chokephaibulkit, Kulkanya; Santos-Lima, Eduardo

    2011-04-01

    To assess a new, fully-liquid, hexavalent DTaP-IPV-Hep B-PRP-T vaccine (diphtheria toxoid (D), tetanus toxoid (T), acellular pertussis (aP), inactivated poliovirus (IPV), hepatitis B (Hep B), and Haemophilus influenzae type b polysaccharide conjugated to tetanus protein (PRP-T) antigens) compared to a licensed DTaP-IPV-Hep B//PRP-T vaccine following primary series co-administration with a 7-valent pneumococcal conjugate vaccine (PCV7). This was a randomized, phase III, observer-blind study in Thai infants (N=412), who received DTaP-IPV-Hep B-PRP-T or DTaP-IPV-Hep B//PRP-T at 2, 4, and 6 months of age, co-administered with PCV7. All received Hep B at birth. Non-inferiority for Hep B ≥ 10 mIU/ml and PRP ≥0.15μg/ml was analyzed (DTaP-IPV-Hep B-PRP-T relative to DTaP-IPV-Hep B//PRP-T) at 1 month post-primary. Seroprotection/seroconversion and geometric mean titers (GMTs) were analyzed descriptively for all hexavalent components. Safety was evaluated from parental reports. Anti-Hep B and anti-PRP antibody seroprotection rates were high for DTaP-IPV-Hep B-PRP-T (n=189) and DTaP-IPV-Hep B//PRP-T (n=190), and non-inferiority was demonstrated. Anti-D and anti-T ≥ 0.01 IU/ml, anti-polio types 1, 2, and 3 ≥ 8 (1/dil), and anti-PT and anti-FHA seroconversion were high and similar in each group. For DTaP-IPV-Hep B-PRP-T and DTaP-IPV-Hep B//PRP-T, anti-Hep B ≥ 100 mIU/ml was 98.4% and 99.5% (GMTs 2477 and 2442 mIU/ml), respectively; anti-PRP ≥ 1.0 μg/ml was 85.2% and 71.1% (GMTs 5.07 and 2.41 μg/ml), respectively. Safety profiles were comparable. There were no vaccine-related serious adverse events. Following co-administration with PCV7 the investigational DTaP-IPV-Hep B-PRP-T vaccine was safe and immunogenic. Non-inferiority to DTaP-IPV-Hep B//PRP-T was shown for Hep B and PRP. Copyright © 2011 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  2. Avaliação da resposta humoral à vacina pneumocócica 7-valente em crianças com Aids Evaluación de la vacuna neumocócica 7-valente en la respuesta humoral de niños con SIDA Evaluation of humoral response to heptavalent pneumococcal conjugate vaccine in HIV-infected children

    Directory of Open Access Journals (Sweden)

    Isabel de Camargo Costa

    2008-10-01

    Paulo (Sureste de Brasil, en 2002-2003. La dosis de anticuerpos IgG contra los polisacáridos de la cápsula neumocócica fue realizada por medio de ensayo inmuno enzimático (ELISA. Los anticuerpos fueron dosificados inmediatamente antes y un mes después de la aplicación de la segunda dosis de la vacuna. Se utilizaron dos criterios para evaluar la respuesta a la vacuna: títulos de anticuerpos ? 1,3 ?g/mL en la serología post-inmunización y aumento ?4 veces en los títulos de la serología post-inmunización con relación a la pre-inmunización. RESULTADOS: Para el primer criterio (?1,3 ?g/mL, 26 (65% niños obtuvieron respuesta serológica con la vacuna, 12 (30% de ellas presentaron títulos de IgG post-inmunización en niveles de por lo menos 1,3 ?g/mL para todos los serotipos. Para el segundo criterio (incremento >4 veces en los títulos para cuatro serotipos o mas, se obtuvo respuesta serológica en 15 (37,5% niños. CONCLUSIONES: La respuesta frente a la vacuna fue considerada satisfactoria, con aumento estadísticamente significativo de los títulos geométricos promedios post-vacunales con relación a los pre-vacunales para todos los serotipos estudiados.OBJECTIVE: Invasive pneumococcal disease is a major cause of death in HIV-infected children. The objective of the study was to assess the quantitative antibody response to the seven pneumococcal serotypes of heptavalent pneumococcal conjugate vaccine in a group of HIV-infected children. METHODS: Study comprising 40 HIV-infected children aged between 2 and 9 years followed up in a specialized outpatient clinic in São Paulo, Brazil, between 2002 and 2003. Enzyme immunoassay (ELISA was used to measure IgG antibody titers against pneumococcus capsule. Antibodies were measured immediately before and 1 month after the second dose of the vaccine. Two response criteria were used: IgG titers >1.3 µg/mL in the post-immunization serology and an increase of at least 4-fold in post- compared to pre

  3. 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

  4. [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.

  5. Molecular epidemiology of pneumococcal colonization in response to pneumococcal conjugate vaccination in children with recurrent acute otitis media.

    NARCIS (Netherlands)

    D. Bogaert (Debby); R.H. Veenhoven (Reinier); M. Sluijter (Marcel); W.J. Wannet; G.T. Rijkers; T.J. Mitchell; S.C. Clarke; W.H.F. Goessens (Wil); A.G. Schilder (Anne); E.A. Sanders (Elisabeth); R. de Groot (Ronald); P.W.M. Hermans (Peter)

    2005-01-01

    textabstractA randomized double-blind trial with a 7-valent pneumococcal conjugate vaccine was conducted in The Netherlands among 383 children, aged 1 to 7 years, with a history of recurrent acute otitis media. No effect of vaccination on the pneumococcal colonization rate was found. However, a shif

  6. Molecular epidemiology of pneumococcal colonization in response to pneumococcal conjugate vaccination in children with recurrent acute otitis media.

    NARCIS (Netherlands)

    Bogaert, D.; Veenhoven, R.H.; Sluijter, M.; Wannet, W.J.B.; Rijkers, G.T.; Mitchell, T.J.; Clarke, S.C.; Goessens, W.H.F.; Schilder, A.G.M.; Sanders, E.A.M.; Groot, R. de; Hermans, P.W.M.

    2005-01-01

    A randomized double-blind trial with a 7-valent pneumococcal conjugate vaccine was conducted in The Netherlands among 383 children, aged 1 to 7 years, with a history of recurrent acute otitis media. No effect of vaccination on the pneumococcal colonization rate was found. However, a shift in serotyp

  7. 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 vacc

  8. Molecular epidemiology of pneumococcal colonization in response to pneumococcal conjugate vaccination in children with recurrent acute otitis media.

    NARCIS (Netherlands)

    D. Bogaert (Debby); R.H. Veenhoven (Reinier); M. Sluijter (Marcel); W.J. Wannet; G.T. Rijkers; T.J. Mitchell; S.C. Clarke; W.H.F. Goessens (Wil); A.G. Schilder (Anne); E.A. Sanders (Elisabeth); R. de Groot (Ronald); P.W.M. Hermans (Peter)

    2005-01-01

    textabstractA randomized double-blind trial with a 7-valent pneumococcal conjugate vaccine was conducted in The Netherlands among 383 children, aged 1 to 7 years, with a history of recurrent acute otitis media. No effect of vaccination on the pneumococcal colonization rate was found. However, a

  9. Changes in fluoroquinolone-resistant Streptococcus pneumoniae after 7-valent conjugate vaccination, Spain.

    Science.gov (United States)

    de la Campa, Adela G; Ardanuy, Carmen; Balsalobre, Luz; Pérez-Trallero, Emilio; Marimón, Jose M; Fenoll, Asunción; Liñares, Josefina

    2009-06-01

    Among 4,215 Streptococcus pneumoniae isolates obtained in Spain during 2006, 98 (2.3%) were ciprofloxacin resistant (3.6% from adults and 0.14% from children). In comparison with findings from a 2002 study, global resistance remained stable. Low-level resistance (30 isolates with MIC 4-8 microg/mL) was caused by a reserpine-sensitive efflux phenotype (n = 4) or single topoisomerase IV (parC [n = 24] or parE [n = 1]) changes. One isolate did not show reserpine-sensitive efflux or mutations. High-level resistance (68 isolates with MIC >or=16 microg/mL) was caused by changes in gyrase (gyrA) and parC or parE. New changes in parC (S80P) and gyrA (S81V, E85G) were shown to be involved in resistance by genetic transformation. Although 49 genotypes were observed, clones Spain9V-ST156 and Sweden15A-ST63 accounted for 34.7% of drug-resistant isolates. In comparison with findings from the 2002 study, clones Spain14-ST17, Spain23F-ST81, and ST8819F decreased and 4 new genotypes (ST9710A, ST57016, ST43322, and ST71733) appeared in 2006.

  10. Efficacy of conjugate vaccines in pneumococcal infection prevention

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    A. L. Perova

    2014-01-01

    Full Text Available The problem of pneumococcal infection is actual for many countries of the world in connection with high incidence and mortality. Vaccination by the 7-valent conjugated pneumococcal vaccine of children till 2 years is available in Russia since 2009, 13-valent – since 2012. Objectives – an assessment of clinical and epidemiological efficacy in pneumococcal infection prevention infection by catamnesis after 7-valent conjugated pneumococcal vaccine application. Observation over incidence of pneumonia and otitis of 50 children imparted against a pneumococcal infection is made. The indicator of density of incidence of pneumonia in group of the imparted made 9,7 on 1000 (95% of CI; 9,1–10,3 in group of comparison – 92,6 on 1000 (95% of CI; 91,3–93,9. Index of efficacy of vaccination concerning pneumonia of any etiology – 9,5, effectiveness ratio – 89,5%. The indicator of density of incidence of otitis at the imparted was 1,8 times less – 155,3 on 1000 (95% of CI; 150,9–155,7 in group of comparison – 263,9 on 1000 (95% of CI; 261,7–266,1. The index and vaccination effectiveness ratio concerning acute otitis media made 1,8 and 44,3%. Thus, vaccination against pneumococcal infection is effective as concerning community acquired pneumonia, and acute otitis media of any etiology.

  11. Meeting the challenge: prevention of pneumococcal disease with conjugate vaccines

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    Echániz-Avilés Irma Gabriela

    2001-01-01

    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.html

  12. Epidemiologic impact and cost-effectiveness of universal infant vaccination with a 7-valent conjugated pneumococcal vaccine in the Netherlands

    NARCIS (Netherlands)

    Bos, JM; Rumke, H; Welte, R; Postma, MJ

    2003-01-01

    Background: Streptococcus pneumoniae is one of the main causes of bacterial meningitis, bacteremia, pneumonia, and otitis media in the Netherlands. These diseases lead to substantial mortality, morbidity, and costs. The societal impact is especially severe because most cases occur in very young infa

  13. 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...

  14. Recommendation for use of the newly introduced pneumococcal protein conjugate vaccines in Korea

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    Eun Hwa Choi

    2011-04-01

    Full Text Available Streptococcus pneumoniae remains a leading cause of invasive infections including bacteremia and meningitis, as well as mucosal infections such as otitis media and pneumonia among children and adults. The 7-valent pneumococcal conjugate vaccine (PCV7 was licensed for use among infants and young children in many countries including Korea. The routine use of PCV7 has resulted in a decreased incidence of invasive pneumococcal disease (IPD by the vaccine serotypes among the vaccinees and substantial declines in IPD among unvaccinated populations such as older children and adults as well. In addition, there are increasing evidences to suggest that routine immunization with PCV7 is changing the epidemiology of pneumococcal diseases such as serotype distribution of IPD, nasopharyngeal colonization, and antibiotic resistance patterns. In contrast, there is an increase in the number of IPDs caused by nonvaccine serotypes, though it is much smaller than overall declines of vaccine serotype diseases. Several vaccines containing additional serotypes have been developed and tested clinically in order to expand the range of serotypes of Streptococcus pneumoniae. Recently two new pneumococcal protein conjugate vaccines, 10-valent pneumococcal conjugate vaccine (PCV10 and 13-valent pneumococcal conjugate vaccine (PCV13, have been approved for use in several countries including Korea. This report summarizes the recommendations approved by the Committee on Infectious Diseases, the Korean Pediatric Society.

  15. Serotype-specific changes in invasive pneumococcal disease after pneumococcal conjugate vaccine introduction

    DEFF Research Database (Denmark)

    Feikin, Daniel R; Kagucia, Eunice W; Loo, Jennifer D;

    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-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...

  16. Risk factors for pneumococcal nasopharyngeal colonization before and after pneumococcal conjugate vaccination in persons with HIV: brief report.

    Science.gov (United States)

    Öbrink-Hansen, Kristina; Søgaard, Ole S; Harboe, Zitta B; Schønheyder, Henrik C

    2012-04-01

    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.

  17. Economic evaluation of pneumococcal conjugate vaccination in The Gambia

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    Kim Sun-Young

    2010-09-01

    Full Text Available Abstract Background Gambia is the second GAVI support-eligible country to introduce the 7-valent pneumococcal conjugate vaccine (PCV7, but a country-specific cost-effectiveness analysis of the vaccine is not available. Our objective was to assess the potential impact of PCVs of different valences in The Gambia. Methods We synthesized the best available epidemiological and cost data using a state-transition model to simulate the natural histories of various pneumococcal diseases. For the base-case, we estimated incremental cost (in 2005 US dollars per disability-adjusted life year (DALY averted under routine vaccination using PCV9 compared to no vaccination. We extended the base-case results for PCV9 to estimate the cost-effectiveness of PCV7, PCV10, and PCV13, each compared to no vaccination. To explore parameter uncertainty, we performed both deterministic and probabilistic sensitivity analyses. We also explored the impact of vaccine efficacy waning, herd immunity, and serotype replacement, as a part of the uncertainty analyses, by assuming alternative scenarios and extrapolating empirical results from different settings. Results Assuming 90% coverage, a program using a 9-valent PCV (PCV9 would prevent approximately 630 hospitalizations, 40 deaths, and 1000 DALYs, over the first 5 years of life of a birth cohort. Under base-case assumptions ($3.5 per vaccine, compared to no intervention, a PCV9 vaccination program would cost $670 per DALY averted in The Gambia. The corresponding values for PCV7, PCV10, and PCV13 were $910, $670, and $570 per DALY averted, respectively. Sensitivity analyses that explored the implications of the uncertain key parameters showed that model outcomes were most sensitive to vaccine price per dose, discount rate, case-fatality rate of primary endpoint pneumonia, and vaccine efficacy against primary endpoint pneumonia. Conclusions Based on the information available now, infant PCV vaccination would be expected to reduce

  18. 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.

  19. [Pneumococcal vaccines. New conjugate vaccines for adults].

    Science.gov (United States)

    Campins Martí, Magda

    2015-11-01

    Pneumococcal infections are a significant cause of morbidity and mortality, and are one of the 10 leading causes of death worldwide. Children under 2 years have a higher incidence rate, followed by adults over 64 years. The main risk group are individuals with immunodeficiency, and those with anatomical or functional asplenia, but can also affect immunocompetent persons with certain chronic diseases. Significant progress has been made in the last 10 years in the prevention of these infections. Until a few years ago, only the 23-valent non-conjugate pneumococcal vaccine was available. Its results were controversial in terms of efficacy and effectiveness, and with serious limitations on the type of immune response induced. The current possibility of using the 13-valent conjugate vaccine in adults has led to greater expectations in improving the prevention of pneumococcal disease in these age groups. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  20. 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

  1. Conjugate Meningococcal Vaccines Development: GSK Biologicals Experience

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    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.

  2. 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

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

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    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

  4. 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

  5. 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.

  6. Meningococcal conjugate vaccines: optimizing global impact

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    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

  7. 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.

  8. How to compare the efficacy of conjugate vaccines to prevent acute otitis media?

    Science.gov (United States)

    De Wals, Philippe; Erickson, Lonny; Poirier, Béatrice; Pépin, Jacques; Pichichero, Michael E

    2009-05-11

    Although the currently available 7-valent pneumococcal conjugate vaccine (PCV7-CRM(197)) has been primarily designed for the prevention of invasive pneumococcal disease, it has also demonstrated the potential to prevent acute otitis media (AOM) and its associated complications. A candidate 11-valent pneumococcal conjugate vaccine (PCV11-HiD), which utilizes Haemophilus influenzae (Hi)-derived protein D as a carrier has demonstrated the ability to prevent AOM caused by not only vaccine serotypes of Streptococcus pneumoniae (Sp), but also those caused by Hi. The methodological, clinical, and epidemiological factors influencing results of vaccine trials for AOM prevention were reviewed and a model-based approach was developed, in order to assess the relative efficacy of different vaccine formulations. Six randomized trials having AOM as a measured outcome were identified. Vaccine efficacy (VE) ranged from -1% to 34% for all-cause AOM and between 56% and 64% for AOM caused by vaccine-type Sp. Using otopathogen-specific VE rates from the FinOM and POET trials and otopathogen distributions observed in three relatively unbiased studies, VE against all-cause AOM episodes under different scenarios was modeled. The most important factor explaining variation in VE estimates was bacterial replacement, which was present in the PCV7-CRM(197) FinOM study but not in the PCV11-HiD POET study. Another contributing factor was increased protection conferred against Hi AOM by protein D. Geographical variation in the distribution of otopathogens was a third factor explaining differences between trials. More studies on the current aetiology of AOM need to be performed to accurately predict the marginal benefit of a switch from PCV7-CRM(197) to the newly licensed PCV10-HiD-DiT or to the future PCV13-CRM(197).

  9. Evolving microbiology and molecular epidemiology of acute otitis media in the pneumococcal conjugate vaccine era.

    Science.gov (United States)

    Pichichero, Michael E; Casey, Janet R

    2007-10-01

    The addition of the 7-valent pneumococcal conjugate vaccine (PCV7) to the routine immunization schedule in the United States for infants has produced a much more favorable impact on the incidence of acute otitis media (AOM) than anticipated. Because the serotypes included in PCV7 were those most frequently expressing antibiotic resistance in 2001, predictions were made that up to 98% of pneumococcal AOM episodes would be caused by penicillin susceptible strains. However, recent studies have shown that the benefits of PCV7 are becoming eroded. Replacement serotypes of pneumococci have emerged, expressing polysaccharide capsules different from those included in PCV7, with increasing frequency. These replacement strains are coming to dominate in the nasopharynx and in AOM isolates (and in invasive disease). Expansion in the isolation of serotypes 3, 7F, 15B/C/F, 19A, 22F, 33F, and 38 has been described in various surveillance systems. Pneumococcal strains expressing non-PCV7 capsular serotypes also appear to be rapidly acquiring resistance to penicillin and other antibiotics. Emergence of strains of pneumococci expressing non-PCV7 capsular serotypes is occurring by multiple mechanisms including capsular switching as suggested by molecular epidemiology studies. Expansion of the number of serotypes included in pneumococcal conjugate vaccines is needed to sustain a long-term benefit from immunization against these bacteria.

  10. Bacteremia in Children 3 to 36 Months Old After Introduction of Conjugated Pneumococcal Vaccines.

    Science.gov (United States)

    Greenhow, Tara L; Hung, Yun-Yi; Herz, Arnd

    2017-04-01

    In June 2010, Kaiser Permanente Northern California replaced all 7-valent pneumococcal conjugate vaccine (PCV7) vaccines with the 13-valent pneumococcal conjugate vaccine (PCV13). Our objectives were to compare the incidence of bacteremia in children 3 to 36 months old by 3 time periods: pre-PCV7, post-PCV7/pre-PCV13, and post-PCV13. We designed a retrospective review of the electronic medical records of all blood cultures collected on children 3 to 36 months old at Kaiser Permanente Northern California from September 1, 1998 to August 31, 2014 in outpatient clinics, in emergency departments, and in the first 24 hours of hospitalization. During the study period, 57 733 blood cultures were collected in the population of children 3 to 36 months old. Implementation of routine immunization with the pneumococcal conjugate vaccine resulted in a 95.3% reduction of Streptococcus pneumoniae bacteremia, decreasing from 74.5 to 10 to 3.5 per 100 000 children per year by the post-PCV13 period. As pneumococcal rates decreased, Escherichia coli, Salmonella spp, and Staphylococcus aureus caused 77% of bacteremia. Seventy-six percent of all bacteremia in the post-PCV13 period occurred with a source. In the United States, routine immunizations have made bacteremia in the previously healthy toddler a rare event. As the incidence of pneumococcal bacteremia has decreased, E coli, Salmonella spp, and S aureus have increased in relative importance. New guidelines are needed to approach the previously healthy febrile toddler in the outpatient setting. Copyright © 2017 by the American Academy of Pediatrics.

  11. The impact of B-cell perturbations on pneumococcal conjugate vaccine response in HIV-infected adults.

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    Thomas G Johannesson

    Full Text Available Untreated HIV infection results in severe perturbations of the B-cell population and hyporesponsiveness to vaccination. We studied associations between circulating B-cell subsets and antibody response to pneumococcal conjugate vaccine in treated and untreated HIV patients.Ninety-five HIV-infected adults were grouped according to antiretroviral therapy (ART and CD4+ cell count as follows: 20 ART-naïve (no prior ART, 62 ART-responders (received ART, and CD4 count >500 cells/µl, and 13 impaired responders (received ART for more than 3 years, and CD4 count <500 cells/µl. All subjects were immunized twice with double-dose 7-valent pneumococcal conjugate vaccine with or without 1 mg CPG 7909 (toll-like receptor 9 agonist at baseline and after three months. Pre-vaccination B-cell subpopulations were assessed by flow cytometry. Serum IgG concentrations for vaccine serotypes were quantified by ELISA at baseline and 3, 4, and 9 months post-vaccination. ART responders had more isotype-switched memory B cells and more marginal-zone (MZ-like B cells compared with impaired responders. Furthermore, ART-naïve patients had higher concentration of transitional B cells and plasmablasts compared with B cells of other patient groups. The concentration of MZ-like, isotype switched memory cells and plasmablasts correlated positively with post-vaccination IgG concentration at 3, 4, and 9 months. Low concentrations of isotype-switched memory B cells was the strongest independent predictor of poor pneumococcal conjugate vaccine responsiveness, emphasizing that B-cell subset disturbances are associated with poor vaccine response among HIV-infected patients.

  12. [Conjugate vaccines against bacterial infections: typhoid fever].

    Science.gov (United States)

    Paniagua, J; García, J A; López, C R; González, C R; Isibasi, A; Kumate, J

    1992-01-01

    Capsular polysaccharides have been studied as possible vaccines against infectious diseases. However, they are capable to induce only short-run protection because of their T-independent properties and they would not be protective against infection in high-risk populations. The alternative to face this problem is to develop methods to join covalently the polysaccharide and proteins to both increase the immunogenicity of and to confer the property of T-dependence to this antigen. In order to obtain a conjugate vaccine against typhoid fever, in our laboratory we have tried to synthesize a conjugate immunogen between the Vi antigen and porins from Salmonella typhi.

  13. 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

  14. Cost-effectiveness of 2 + 1 dosing of 13-valent and 10-valent pneumococcal conjugate vaccines in Canada

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    Earnshaw Stephanie R

    2012-04-01

    Full Text Available Abstract Background Thirteen-valent pneumococcal conjugate vaccine (PCV13 and 10-valent pneumococcal conjugate vaccine (PCV10 are two recently approved vaccines for the active immunization against Streptococcus pneumoniae causing invasive pneumococcal disease in infants and children. PCV13 offers broader protection against Streptococcus pneumoniae; however, PCV10 offers potential protection against non-typeable Haemophilus influenza (NTHi. We examined public health and economic impacts of a PCV10 and PCV13 pediatric national immunization programs (NIPs in Canada. Methods A decision-analytic model was developed to examine the costs and outcomes associated with PCV10 and PCV13 pediatric NIPs. The model followed individuals over the remainder of their lifetime. Recent disease incidence, serotype coverage, population data, percent vaccinated, costs, and utilities were obtained from the published literature. Direct and indirect effects were derived from 7-valent pneumococcal vaccine. Additional direct effect of 4% was attributed to PCV10 for moderate to severe acute otitis media to account for potential NTHi benefit. Annual number of disease cases and costs (2010 Canadian dollars were presented. Results In Canada, PCV13 was estimated to prevent more cases of disease (49,340 when considering both direct and indirect effects and 7,466 when considering direct effects only than PCV10. This translated to population gains of 258 to 13,828 more quality-adjusted life-years when vaccinating with PCV13 versus PCV10. Annual direct medical costs (including the cost of vaccination were estimated to be reduced by $5.7 million to $132.8 million when vaccinating with PCV13. Thus, PCV13 dominated PCV10, and sensitivity analyses showed PCV13 to always be dominant or cost-effective versus PCV10. Conclusions Considering the epidemiology of pneumococcal disease in Canada, PCV13 is shown to be a cost-saving immunization program because it provides substantial public

  15. Carriage of streptococcus pneumoniae 3 years after start of vaccination program, the Netherlands

    NARCIS (Netherlands)

    Spijkerman, J.; van Gils, E.J.M.; Veenhoven, R.H.; Hak, E.; Yzerman, E.P.F.; van der Ende, A.; Wijmenga-Monsuur, A.J.; van den Dobbelsteen, G.P.J.M.; Sanders, E.A.M.

    2011-01-01

    To evaluate the effectiveness of the 7-valent pneumococcal conjugate vaccine (PCV7) program, we conducted a cross-sectional observational study on nasopharyngeal carriage of Streptococcus pneumoniae 3 years after implementation of the program in the Netherlands. We compared pneumococcal serotypes in

  16. 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

  17. Safety and immunogenicity of three doses of an eleven-valent diphtheria toxoid and tetanus protein – conjugated pneumococcal vaccine in Filipino infants

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    Käyhty Helena

    2003-08-01

    Full Text Available Abstract Background An 11-valent pneumococcal conjugate vaccine could provide significantly larger reduction in pneumococcal disease burden than the currently available 7-valent vaccine formulation in many countries. Methods In total, 50 infants were enrolled to this open, uncontrolled study, which evaluated the safety and immunogenicity of an aluminium adjuvanted 11-valent mixed-carrier diphtheria toxoid or tetanus protein-conjugated vaccine (11-PncTD when administered in three doses at 6, 10 and 14 weeks of age simultaneously with DTwP//PRP-T and OPV vaccines in Filipino infants. Results The rates of local reactions between the two injection sites, those associated with the 11-PncTD vaccine and those with the DTwP//PRP-T were almost of equal frequency for all three vaccine doses except for induration, which was significantly more common in the DTP//PRP-T injection site. Fever was present in 39%, 22% and 21% of infants following each of the three doses. Antibody responses were determined by an enzyme immunoassay method before the first vaccination and after the three doses. The vaccine elicited a significant anti-pneumococcal polysaccharide antibody response against all serotypes included in the vaccine, except for type 14, for which the pre-vaccination geometric mean antibody concentration (GMC was high (1.61 μg/ml. The GMCs one month after the vaccination series ranged from 1.1 micrograms/ml for type 6B to 23.4 μg/ml for type 4. Conclusion The 11-PncTD vaccine is safe, well-tolerated and immunogenic. The effectiveness of the non-adjuvanted formulation of the vaccine in preventing pneumonia is currently being evaluated in the Philippines.

  18. Progress towards meningitis prevention in the conjugate vaccines era

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    Cristina Aparecida Borges Laval

    2003-10-01

    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.

  19. Progress towards meningitis prevention in the conjugate vaccines era

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    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.

  20. Dosing Schedules for Pneumococcal Conjugate Vaccine

    Science.gov (United States)

    2014-01-01

    Since second generation pneumococcal conjugate vaccines (PCVs) targeting 10 and 13 serotypes became available in 2010, the number of national policy makers considering these vaccines has steadily increased. An important consideration for a national immunization program is the timing and number of doses—the schedule—that will best prevent disease in the population. Data on disease epidemiology and the efficacy or effectiveness of PCV schedules are typically considered when choosing a schedule. Practical concerns, such as the existing vaccine schedule, and vaccine program performance are also important. In low-income countries, pneumococcal disease and deaths typically peak well before the end of the first year of life, making a schedule that provides PCV doses early in life (eg, a 6-, 10- and 14-week schedule) potentially the best option. In other settings, a schedule including a booster dose may address disease that peaks in the second year of life or may be seen to enhance a schedule already in place. A large and growing body of evidence from immunogenicity studies, as well as clinical trials and observational studies of carriage, pneumonia and invasive disease, has been systematically reviewed; these data indicate that schedules of 3 or 4 doses all work well, and that the differences between these regimens are subtle, especially in a mature program in which coverage is high and indirect (herd) effects help enhance protection provided directly by a vaccine schedule. The recent World Health Organization policy statement on PCVs endorsed a schedule of 3 primary doses without a booster or, as a new alternative, 2 primary doses with a booster dose. While 1 schedule may be preferred in a particular setting based on local epidemiology or practical considerations, achieving high coverage with 3 doses is likely more important than the specific timing of doses. PMID:24336059

  1. Postlicensure surveillance for pre-specified adverse events following the 13-valent pneumococcal conjugate vaccine in children.

    Science.gov (United States)

    Tseng, Hung Fu; Sy, Lina S; Liu, In-Lu Amy; Qian, Lei; Marcy, S Michael; Weintraub, Eric; Yih, Katherine; Baxter, Roger; Glanz, Jason M; Donahue, James; Naleway, Allison; Nordin, James; Jacobsen, Steven J

    2013-05-24

    Although no increased risk was detected for serious adverse events in the prelicensure trials for the 13-valent pneumococcal vaccine, Prevnar 13(®) (PCV13), continued monitoring of rare but serious adverse events is necessary. A surveillance system using cohort study design was set up to monitor safety of PCV13 immediately after it was included in the childhood immunization program in the United States. The exposed population included children of 1 month to 2 years old who received PCV13 from April, 2010 to January, 2012 from the eight managed care organizations participating in the Vaccine Safety Datalink Project in the United States. The historical unexposed population was children of the same age who received the 7-valent pneumococcal conjugate vaccine Prevnar 7(®) (PCV7) in 2007 (or 2005 depending on the outcome of interest) to 2009. The risk of pre-specified adverse events in the risk window following PCV13 was repeatedly compared to that in the historical comparison group. The number of doses included in the study was 599,229. No increased risk was found for febrile seizures, urticaria or angioneurotic edema, asthma, thrombocytopenia, or anaphylaxis. An increased risk for encephalopathy was not confirmed following the medical record review. The relative risk for Kawasaki disease in 0-28 days following vaccination was 1.94 (95% confidence interval: 0.79-4.86), comparing PCV13 to PCV7. Comparing to PCV7 vaccine, we identified no significant increased risk of pre-specified adverse events in the Vaccine Safety Datalink study cohort. The possible association between PCV13 and Kawasaki disease may deserve further investigation.

  2. 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. Partic

  3. 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.

  4. Prophylactic antipyretics for prevention of febrile seizures following vaccination.

    Science.gov (United States)

    Monfries, Nicholas; Goldman, Ran D

    2017-02-01

    Question Parents of a 12-month-old boy are bringing their son in to my family practice clinic for his well-baby visit. As the infant is due for his 12-month vaccine series, the parents are concerned after hearing about the association between certain vaccinations and an increased risk of febrile seizures, and are wondering if they should administer prophylactic antipyretics to decrease the risk of febrile seizure. What vaccinations are associated with increased risk of febrile seizure, and is there evidence supporting prophylactic administration of antipyretics to prevent febrile seizures? Answer Vaccinations associated with increased risk of febrile seizure include the following: the measles-mumps-rubella vaccine; the measles-mumps-rubella-varicella vaccine; the combined diphtheria, tetanus, acellular pertussis, polio, and Haemophilus influenzae type b vaccine; the whole-cell pertussis vaccine; the 7-valent pneumococcal conjugate vaccine; and concomitant administration of the trivalent inactivated influenza vaccine with either the 7-valent pneumococcal conjugate vaccine or the diphtheria, tetanus, and acellular pertussis vaccine. Despite being a higher-risk group, children receiving these vaccinations should not receive prophylactic antipyretics, as no statistically significant reduction in the rate of febrile seizures has been documented, and prophylactic antipyretic use potentially decreases the immune response to certain vaccines. Copyright© the College of Family Physicians of Canada.

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

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    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

  6. Impact of the 13-valent pneumococcal conjugate vaccine on chronic sinusitis associated with Streptococcus pneumoniae in children.

    Science.gov (United States)

    Olarte, Liset; Hulten, Kristina G; Lamberth, Linda; Mason, Edward O; Kaplan, Sheldon L

    2014-10-01

    The widespread use of the 7-valent pneumococcal conjugate vaccine has been associated with epidemiologic changes of mucosal and invasive pneumococcal disease. No study describes the impact of 13-valent pneumococcal conjugate vaccine (PCV13) on chronic sinusitis in children. We describe changes in epidemiology of Streptococcus pneumoniae chronic sinusitis after the introduction of PCV13 at Texas Children's Hospital. We identified patients sinus culture for S. pneumoniae who underwent endoscopic sinus surgery because of chronic sinusitis from August 2008 to December 2013 at Texas Children's Hospital. Isolates were serotyped by the capsular swelling method. Demographic and clinical information was collected retrospectively. The χ test and Fisher's exact test were used to analyze dichotomous variables. We identified 91 cases of chronic sinusitis with positive sinus culture for S. pneumoniae. Sixty-one (67%) isolates were non-PCV13 serotypes. PCV13 cases decreased 31% in the post-PCV13 period (P = 0.003). Serotype 19A decreased 27% in the post-PCV13 period (P = 0.007), but accounted for all the isolates with penicillin minimal inhibitory concentration ≥ 4 μg/mL and ceftriaxone minimal inhibitory concentration ≥ 2 μg/mL. Serotypes 19A (38%) and 15C (17%) were the most common in the pre- and post-PCV13 periods, respectively. The most common organism co-isolated was Haemophilus influenzae (52%). Isolation of Prevotella spp. increased in the post-PCV13 period (P = 0.02). S. pneumoniae continues to represent an important pathogen in chronic sinusitis in children sinusitis at Texas Children's Hospital. We also observed a substantial reduction of PCV13 serotypes, predominantly serotype 19A.

  7. Hypothesis: conjugate vaccines may predispose children to autism spectrum disorders.

    Science.gov (United States)

    Richmand, Brian J

    2011-12-01

    The first conjugate vaccine was approved for use in the US in 1988 to protect infants and young children against the capsular bacteria Haemophilus influenzae type b (Hib). Since its introduction in the US, this vaccine has been approved in most developed countries, including Denmark and Israel where the vaccine was added to their national vaccine programs in 1993 and 1994, respectively. There have been marked increases in the reported prevalence of autism spectrum disorders (ASDs) among children in the US beginning with birth cohorts in the late 1980s and in Denmark and Israel starting approximately 4-5 years later. Although these increases may partly reflect ascertainment biases, an exogenous trigger could explain a significant portion of the reported increases in ASDs. It is hypothesized here that the introduction of the Hib conjugate vaccine in the US in 1988 and its subsequent introduction in Denmark and Israel could explain a substantial portion of the initial increases in ASDs in those countries. The continuation of the trend toward increased rates of ASDs could be further explained by increased usage of the vaccine, a change in 1990 in the recommended age of vaccination in the US from 15 to 2 months, increased immunogenicity of the vaccine through changes in its carrier protein, and the subsequent introduction of the conjugate vaccine for Streptococcus pneumoniae. Although conjugate vaccines have been highly effective in protecting infants and young children from the significant morbidity and mortality caused by Hib and S. pneumoniae, the potential effects of conjugate vaccines on neural development merit close examination. Conjugate vaccines fundamentally change the manner in which the immune systems of infants and young children function by deviating their immune responses to the targeted carbohydrate antigens from a state of hypo-responsiveness to a robust B2 B cell mediated response. This period of hypo-responsiveness to carbohydrate antigens coincides

  8. 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.

  9. Development of Vi conjugate - a new generation of typhoid vaccine.

    Science.gov (United States)

    Szu, Shousun Chen

    2013-11-01

    Typhoid fever remains to be a serious disease burden worldwide with an estimated annual incidence about 20 million. The licensed vaccines showed moderate protections and have multiple deficiencies. Most important of all, none of the licensed typhoid vaccines demonstrated protection for children under 5 years old. These limitations impeded successful implementation of typhoid vaccination programs. To improve immunogenicity Vi was conjugated to rEPA, a recombinant exoprotein A from Pseudomonas aeruginosa. Vi-rEPA showed higher and longer lasting anti-Vi IgG in adults and children than Vi alone in high endemic areas. In school-age children and adults, the immunity persisted more than 8 years. In a double-blind, placebo-controlled and randomized efficacy trial in 2- to 5-year-old children, Vi-rEPA conferred 89% protective efficacy against typhoid fever and the protection lasted at least 4 years. When given concomitantly with infant routine vaccines, Vi-rEPA was safe, immunogenic and showed no interference with the routine vaccines. Vi conjugate vaccine was also attempted and successfully demonstrated by several other laboratories and manufactures. Using either rEPA or different carrier proteins, such as diphtheria or tetanus toxoid, recombinant diphtheria toxin (CRM197), the Vi conjugates synthesized was significantly more immunogenic than Vi alone. Recently, two Vi-tetanus toxoid conjugates were licensed in India for all ages, starts as young as 3 month old. This new generation of typhoid vaccine opens up a new era for typhoid prevention and elimination.

  10. Impact of the pneumococcal conjugate vaccine on serotype distribution and susceptibility trends of pediatric non-invasive Streptococcus pneumoniae isolates in Tokai, Japan over a 5-year period.

    Science.gov (United States)

    Okade, Hayato; Funatsu, Tori; Eto, Maki; Furuya, Yuri; Mizunaga, Shingo; Nomura, Nobuhiko; Mitsuyama, Junichi; Yamagishi, Yuka; Mikamo, Hiroshige

    2014-07-01

    Introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in February 2010 markedly reduced the burden of invasive pneumococcal disease (IPD) and changed serotype distribution in Japan. We investigated the serotype distribution and susceptibility trends of non-invasive Streptococcus pneumoniae isolates collected from pediatric patients. A total of 564 pneumococcal isolates were collected over a 5-year period between 2008 and 2012. The coverage of PCV7 significantly decreased throughout the study period, from 49.3% in period 1 (between June 2008 and April 2009) to 23.4% in period 4 (between October 2011 and March 2012). This change was mainly due to a large decrease in the frequency of 19F (from 20.6% to 9.9%) and 6B (from 10.3% to 2.7%) and an increase in serotype 3 (from 5.1% to 13.5%) and serogroup 15 (from 4.4% to 9.0%). According to serotype replacement, the susceptible ratios of S. pneumoniae to β-lactams increased slightly while macrolide resistance remained high. The high frequency of macrolide-resistant pneumococcal isolates may continue because of the high frequency of erm(B) in replace serotypes such as serotype 3 and serogroup 15. The continuous surveillance study is essential following the introduction of a second generation 13-valent pneumococcal conjugate vaccine (PCV13).

  11. 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 <18years using Nationwide Inpatient Sample and Census data (1997-2013) for four periods based on PCV7 and PCV13 introductions. Relative rates (RR) and 95% confidence intervals (CI) were calculated by age group and sex, comparing PCV7 [early-PCV7 (2001-2005) and late-PCV7 (2006-2009)] and PCV13 (2011-2013) periods with the pre-PCV7 period (1997-1999). Secondary analyses examined changes in pneumococcal, streptococcal, staphylococcal and unspecified empyema. Among children <18years of age, annualized empyema hospitalization rates peaked at 3.6 per 100,000 in the late-PCV7 period compared with 2.1 per 100,000 in the pre-PCV7 period [RR: 1.70 (95% CI: 1.11-2.60)]. However, annualized rates in the post-PCV13 period declined to 2.0 per 100,000, similar to rates in the pre-PCV7 period. Empyema rates among children <2years were lower in the post-PCV13 period compared to the pre-PCV7 period [RR: 0.77 (95% CI: 0.61-0.96)], but rates in the two periods among 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.

  12. 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

  13. 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.

  14. Enhanced decision support for policy makers using a web interface to health-economic models - Illustrated with a cost-effectiveness analysis of nation-wide infant vaccination with the 7-valent pneumococcal conjugate vaccine in the Netherlands

    NARCIS (Netherlands)

    Hubben, G.A.A.; Bos, J.M.; Glynn, D.M.; van der Ende, A.; van Alphen, L.; Postma, M.J.

    2007-01-01

    We have developed a web-based user-interface (web interface) to enhance the usefulness of health-economic evaluations to support decision making (http://pcv.healtheconomics.nl). It allows the user to interact with a health-economic model to evaluate predefined and customized scenarios and perform se

  15. Nasopharyngeal microbial interactions in the era of pneumococcal conjugate vaccination.

    Science.gov (United States)

    Dunne, Eileen M; Smith-Vaughan, Heidi C; Robins-Browne, Roy M; Mulholland, E Kim; Satzke, Catherine

    2013-05-01

    The nasopharynx of children is often colonised by microorganisms such as Streptococcus pneumoniae (the pneumococcus) that can cause infections including pneumonia and otitis media. In this complex environment, bacteria and viruses may impact each other through antagonistic as well as synergistic interactions. Vaccination may alter colonisation dynamics, evidenced by the rise in non-vaccine serotypes following pneumococcal conjugate vaccination. Discovery of an inverse relationship between S. pneumoniae and Staphylococcus aureus carriage generated concern that pneumococcal vaccination could increase S. aureus carriage and disease. Here we review data on co-colonisation of pathogens in the nasopharynx, focusing on S. pneumoniae and the impact of pneumococcal vaccination. Thus far, pneumococcal vaccination has not had a sustained impact on S. aureus carriage but it is associated with an increase in non-typeable Haemophilus influenzae in acute otitis media aetiology. Advances in bacterial and viral detection methodologies have facilitated research in nasopharyngeal microbiology and will aid investigation of potential vaccine-induced changes, particularly when baseline studies can be conducted prior to pneumococcal vaccine introduction.

  16. 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. 

  17. Antipneumococcal vaccination

    Directory of Open Access Journals (Sweden)

    Gian Vincenzo Zuccotti

    2013-06-01

    Full Text Available Streptococcus pneumoniae (SP is a gram-positive bacterium with more than 90 known serotypes causing around 11% of all deaths worldwide in children aged 1-59 months. A new era in prevention of SP-related diseases started in at the beginning of 2000s when a 7-valent pneumococcal conjugate vaccine (PCV7 was recommended as the vaccine of choice in pediatric age. PCV7 dramatically reduced invasive pneumococcal diseases (IPD among children with indirect effects noted among other age groups as well. However, thanks to a strict surveillance network, an increase in non-vaccine serotypes (NVTs causing IPD was noted worldwide and in late 2000s a new second generation vaccine (13-valent pneumococcal conjugate vaccine-PCV13 with an expanded serotype coverage was licensed. Due to the lack of solid effectiveness data, up to know it is difficult to predict how the composition of NVTs will change after the large-scale introduction of PCV13 or whether the characteristics of the serotypes will change. Long-term surveillance of both IPD, pneumonia, acute otitis media and carriage will be crucial to ascertain whether these second generation vaccines are having the desired effect of reducing the incidence of diseases in the long term. Proceedings of the 9th International Workshop on Neonatology · Cagliari (Italy · October 23rd-26th, 2013 · Learned lessons, changing practice and cutting-edge research

  18. Avances en el desarrollo de las vacunas neumocócicas conjugadas Update on Pneumococcal Conjugate Vaccines

    Directory of Open Access Journals (Sweden)

    Wendy Chan-Acón

    2010-07-01

    -valente y los serotipos 3, 6A y 19A. En el caso de la vacuna 13-valente, todos los serotipos están conjugados con el transportador CRM197. Estas nuevas formulaciones pretenden ampliar la cobertura contra el S. pneumoniae, incluyendo serotipos frecuentes en países en vías de desarrollo (serotipo 1 y 5 y serotipos emergentes luego de una década de la vacunación con la vacuna 7-valente, como son: 3, 6A, 17F y 19A.Streptococcus pneumoniae is one of the major pathogens causing invasive and non invasive infections in children younger than 5 years as well as in the elderly. Primary clinical syndromes associated with pneumococcal infections are pneumonia, bacteremia, acute otitis media and meningitis. This microorganism contributes importantly to morbidity and mortality among children under 5 years of age, it is estimated that 1,000, 000 deaths occurs per year in that age range alone, mostly from developing countries, thus becoming a serious public health problem around the globe. In year 2000 the first heptavalent conjugated pneumococcal vaccine was licensed in the United States of America, it differed from the already available polysaccharide pneumococcal vaccine, by its ability to provide an effective immune response for the protection of children under the age of 2. The efficacy of the heptavalent conjugated vaccine reported in initial clinical trials was 97, 4% against invasive pneumococcal disease related to vaccine serotypes (4, 9V, 14, 19F, 23F, 18C and 6B. Different health authorities worldwide, including the European Medicines Agency (EMEA had approved the introduction of a 10-valent formulation which includes all 7 PCV7 serotypes plus serotypes 1, 5 and 7F; 8 serotypes are conjugated with protein D as a novel carrier, an element found in the outer core of the non-typeable Haemophilus influenzae. Another new conjugated vaccine is being assessed by several regulatory entities such as the Food and Drug Administration (FDA and EMEA and in Chile is already approved

  19. 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.

  20. 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

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

    Directory of Open Access Journals (Sweden)

    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

  2. 76 FR 53480 - Prospective Grant of Exclusive License: Conjugate Vaccines Against B. anthracis

    Science.gov (United States)

    2011-08-26

    ... HUMAN SERVICES National Institutes of Health Prospective Grant of Exclusive License: Conjugate Vaccines... factor'' (EF). Although production of an efficient anthrax vaccine is an ultimate goal, the benefits of... therapy of B. anthracis (anthrax) infection by immunization with conjugate vaccines against anthrax...

  3. Effect of the different 13-valent pneumococcal conjugate vaccination uptakes on the invasive pneumococcal disease in children: Analysis of a hospital-based and population-based surveillance study in Madrid, Spain, 2007-2015

    Science.gov (United States)

    Picazo, Juan; Ruiz-Contreras, Jesús; Casado-Flores, Juan; Negreira, Sagrario; Baquero, Fernando; Hernández-Sampelayo, Teresa; Otheo, Enrique; Méndez, Cristina

    2017-01-01

    In the Community of Madrid, the 13-valent pneumococcal conjugate vaccine (PCV13) replaced the 7-valent (PCV7) in the fully government-funded Regional Immunization Program (RIP) in May, 2010, but was later excluded in May, 2012, and included again in January, 2015. These unique changes allowed us to assess the impact of the different pneumococcal vaccination policies on PCV13 uptake in infants and on the incidence rate (IR) of invasive pneumococcal disease (IPD) in children <15 years old. In this prospective, active, surveillance study, we estimated PCV13 uptakes, IR and incidence rate ratios (IRR) for total IPD and for IPD caused by PCV13- and non-PCV13 serotypes in children <15 years, stratified by age, in four periods with different vaccination policies: fully government-funded PCV7 vaccination, fully government-funded PCV13, mixed public/private funding and only private funding. Vaccine uptakes reached 95% in periods with public-funded pneumococcal vaccination, but fell to 67% in the private funding period. Overall, IR of IPD decreased by 68% (p<0.001) in 2014–15, due to 93% reduction in the IR of PCV13-type IPD (p<0.001) without significant changes in non-PCV13-type IPD. A fully government-funded PCV13 vaccination program lead to high vaccine uptake and dramatic reductions in both overall and PCV13-type IPD IR. When this program was switched to private PCV13 vaccination, there was a fall in vaccine coverage and stagnation in the decline of PCV13-type IPD with data suggesting a weakening of herd immunity. PMID:28207888

  4. 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 influenzae and S. pneumoniae meningitis also decreased from 0.66 to 0.08 (p < 0.001), and 0.30 to 0.06 (p < 0.001), respectively. Only 0-2 cases with Neisseria meningitidis were reported each year throughout 2001-2012. The median patient age was 10-12 months in 2001-2011, and became lower in 2012 (2 month old) (p < 0.001). The fatality rate for S. agalactiae is the highest (5.9% (11/187)) throughout 2001-2012 among the four organisms. Risk factors for death and sequelae were convulsions at onset, low CSF glucose, S. agalactiae etiology, and persistent positive CSF culture. Hib vaccine and PCV7 decreased the rate of bacterial meningitis. Earlier introduction of these vaccines may have prevented bacterial meningitis among Japanese children.

  5. Impacts of the 13-Valent Pneumococcal Conjugate Vaccine in Children.

    Science.gov (United States)

    Esposito, Susanna; Principi, Nicola

    2015-01-01

    Applications of the heptavalent pneumococcal conjugate vaccine (PCV7) in the pediatric immunization schedule have dramatically reduced the incidence of pneumococcal diseases in both vaccinated children and unvaccinated individuals of all ages. However, increased infections caused by non-PCV7 serotypes have been reported by several groups. To overcome this problem, new vaccines covering more serotypes including the emerging serotypes have been developed. The 13-valent pneumococcal conjugate vaccine (PCV13) currently covers the 7 PCV7 serotypes (4, 6B, 9V, 14, 18C, 19F, and 23F) and 6 additional serotypes 1, 3, 5, 6A, 7F, and 19A. After the first year of PCV13 applications in the immunization schedule in young children, global evaluation studies demonstrated that PCV13 provided a wider coverage and more effective prevention than PCV7 against invasive pneumococcal diseases (IPDs), mucosal pneumococcal diseases, and pneumococcal carriage. We reviewed the effects of PCV13 in the control of pneumococcal diseases in children based on previous studies.

  6. Invasive pneumococci before the introduction of pneumococcal conjugate vaccine in Turkey: antimicrobial susceptibility, serotype distribution, and molecular identification of macrolide resistance.

    Science.gov (United States)

    Altun, Hatice Uludag; Hascelik, Gülsen; Gür, Deniz; Eser, Özgen Köseoglu

    2015-02-01

    This study evaluates the antimicrobial susceptibilities and serotype distributions of invasive Streptococcus pneumoniae (SP) isolates identified in a Turkish hospital before the introduction of the 7-valent pneumococcal conjugate vaccine (PCV7). The susceptibilities of all isolates were determined by evaluating six antibiotics: penicillin (PEN), ceftriaxone (CRO), levofloxacin (LEV), erythromycin (ERY), clindamycin (CD), and vancomycin (VAN). Serotyping and amplification of macrolide resistance genes were performed. Sixteen (50%) and four (2%) isolates were resistant to PEN and LEV, respectively. No isolates demonstrated VAN resistance. Intermediate resistance to CRO was found in 4% of all invasive isolates. Twenty-three (12.6%) isolates were resistant to ERY. Four (2%) invasive SP isolates demonstrated multidrug resistance. Serogroups 3, 5, 6, 8, 9, and 23 were the most common in both age groups. The potential coverage rates of PCV7 and PCV13 were 44.1 and 66.1% in children and 39.8 and 71.5% in adults, respectively. Continuous surveillance of antimicrobial resistance is required.

  7. 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

  8. Safety experience with heptavalent pneumococcal CRM197-conjugate vaccine (Prevenar) since vaccine introduction.

    Science.gov (United States)

    Center, Kimberly J; Strauss, Ann

    2009-05-26

    Documentation of the safety of any vaccine is of paramount importance given the nature and scale of vaccination as a public health intervention. Prevenar was first approved for use in 2000, and includes seven pneumococcal serotypes conjugated to CRM(197), a carrier protein that has been used safely in multiple conjugate vaccines for more than 20 years. The safety profile of Prevenar was established prior to licensure in 5 clinical trials involving more than 18,000 infants and children. The largest postmarketing study of the safety of Prevenar given concomitantly with other recommended vaccines was conducted in the United States, and included more than 162,000 subjects. This analysis did not suggest any new safety consideration that would alter the risk-benefit balance of the vaccine, and demonstrated the favorable safety profile of Prevenar. To date, global surveillance of spontaneously reported adverse events to the manufacturer after more than 198 million doses distributed has confirmed these findings. The WHO has recommended the priority inclusion of this vaccine in national childhood immunization programs based on both its documented efficacy and safety. We will discuss the importance of monitoring vaccine safety and the methodologies by which this may be done, using Prevenar as an illustrative example.

  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. 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.

  11. 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...

  12. 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

  13. Serotype 3 remains the leading cause of invasive pneumococcal disease in adults in Portugal (2012-2014 despite continued reductions in other 13-valent conjugate vaccine serotypes.

    Directory of Open Access Journals (Sweden)

    Andreia N Horácio

    2016-10-01

    Full Text Available Since 2010 the 13-valent pneumococcal conjugate vaccine (PCV13 replaced the 7-valent vaccine (PCV7 as the leading pneumococcal vaccine used in children through the private sector. Although neither of the PCVs were used significantly in adults, changes in adult invasive pneumococcal disease (IPD were expected due to herd protection. We characterized n=1163 isolates recovered from IPD in adults in 2012-2014 with the goal of documenting possible changes in serotype prevalence and antimicrobial resistance. Among the 54 different serotypes detected, the most frequent, accounting for half of all IPD, were serotypes: 3 (14%, 8 (11%, 19A (7%, 22F (7%, 14 (6% and 7F (5%. The proportion of IPD caused by PCV7 serotypes remained stable during the study period (14%, but was smaller than in the previous period (19% in 2009-2011, p=0.003. The proportion of IPD caused by PCV13 serotypes decreased from 51% in 2012 to 38% in 2014 (p<0.001, mainly due to decreases in serotypes 7F and 19A. However, PCV13 serotype 3 remained relatively stable and the most frequent cause of adult IPD. Non-PCV13 serotypes continued the increase initiated in the late post-PCV7 period, with serotypes 8 and 22F being the most important emerging serotypes. Serotype 15A increased in 2012-2014 (0.7% to 3.5%, p=0.011 and was strongly associated with antimicrobial resistance. However, the decreases in resistant isolates among serotypes 14 and 19A led to an overall decrease in penicillin non-susceptibility (from 17% to 13%, p=0.174 and erythromycin resistance (from 19% to 13%, p=0.034. Introduction of PCV13 in the NIP for children, as well as its availability for adults may further alter the serotypes causing IPD in adults in Portugal and lead to changes in the proportion of resistant isolates.

  14. Pneumococcal conjugate vaccine: a newer vaccine available in India.

    Science.gov (United States)

    Verma, Ramesh; Khanna, Pardeep

    2012-09-01

    Streptococcus pneumoniae, or "pneumococcus," causes pneumonia and infections of the brain and blood that are responsible for significant mortality in children under five years as well as in the elderly. Pneumococcal diseases are a major public health problem worldwide. S. pneumoniae is responsible for 15-50% of all episodes of community-acquired pneumonia, 30-50% of all cases of acute otitis media, and a significant proportion of bacterial meningitis and bacteremia. S. pneumoniae kills at least one million children under the age of five every year, which is more than malaria, AIDS and measles combined. More than 70% of the deaths are in developing countries. In 2007, pneumococcal pneumonia was the leading infectious killer of children worldwide. Perhaps more importantly, pneumonia remains the leading killer of children in India. A recent UNICEF publication estimated that 410,000 children under age 5 y die of pneumonia each year in India, and recent data shows that an estimated 25% of all child deaths in India are due to pneumonia. The fact that this high burden of pneumonia has remained undiminished in India in spite of economic growth and decline in child mortality due to other diseases is a reminder of the importance of tackling pneumonia head-on with dedicated resources. The burden of pneumococcal meningitis, which constitutes about half of all childhood meningitis cases in most settings and a greater proportion of meningitis deaths, makes it difficult to avoid the conclusion that the pneumococcus is responsible for 1 million child deaths each year. Global Alliance for Vaccine and Immunization (GAVI) has offered to supply PCV at a cost of 0.15-0.30 USD/dose to India for inclusion in the national immunization schedule and commits to extending this support until the year 2015. Pneumococcal vaccination in not recommended in children aged 5 and above.

  15. Lessons learned during the development and transfer of technology related to a new Hib conjugate vaccine to emerging vaccine manufacturers.

    Science.gov (United States)

    Hamidi, A; Boog, C; Jadhav, S; Kreeftenberg, H

    2014-07-16

    The incidence of Haemophilus Influenzae type b (Hib) disease in developed countries has decreased since the introduction of Hib conjugate vaccines in their National Immunization Programs (NIP). In countries where Hib vaccination is not applied routinely, due to limited availability and high cost of the vaccines, invasive Hib disease is still a cause of mortality. Through the development of a production process for a Hib conjugate vaccine and related quality control tests and the transfer of this technology to emerging vaccine manufacturers in developing countries, a substantial contribution was made to the availability and affordability of Hib conjugate vaccines in these countries. Technology transfer is considered to be one of the fastest ways to get access to the technology needed for the production of vaccines. The first Hib conjugate vaccine based on the transferred technology was licensed in 2007, since then more Hib vaccines based on this technology were licensed. This paper describes the successful development and transfer of Hib conjugate vaccine technology to vaccine manufacturers in India, China and Indonesia. By describing the lessons learned in this process, it is hoped that other technology transfer projects can benefit from the knowledge and experience gained.

  16. Developing Novel Conjugate HIV-1 Subunit Therapeutic Vaccines.

    Science.gov (United States)

    1996-06-01

    received United States Food and Drug Administration (FDA) approval for use in adults and infants (i.e., Haemophilus influenzae type B, group B...glycoprotein (gp120) conjugate-based vaccine to induce high, long-lasting anti- HLV -1 envelope antibody titers with group specific neutralizing activity...and HLV -1 gpl20 are mixed at a 2.5:1 ratio in a solution of glutaraldehyde in sodium phosphate, pH 6.0, for 2 hours at room temperature. Excess

  17. [Impact of vaccination on acute otitis media].

    Science.gov (United States)

    Blanchard-Rohner, Geraldine; Gervaix, Alain

    2016-02-17

    Acute otitis media (AOM) is an important reason for medical visits and antibiotic use in children, with possible complications. Pneumococcal conjugate vaccines (PCV) have been developed from 2000, with first the apparition of the 7-valent PCV (PCV7), and from 2013, of the 13-valent PCV (PCV13). First developed to prevent invasive pneumococcal infections, they have been shown to reduce the number of AOM as well. PC13 has allowed to reduce the nasopharyngeal carriage of the majority of pneumococcal serotypes found in AOM, with a reduction of 77% of pneumococcal AOM, according to one study.

  18. Meningococcal vaccine A,C,W135,Y: conjugated to tetanus toxoid.

    Science.gov (United States)

    2013-12-01

    A meningococcal vaccine conjugated to protein CRM 197 (Menveo) is the standard vaccine for immunisation against invasive meningococcal infections caused by serogroups A, C, W135 andY, beginning at age 2 years. Nimenrix, another vaccine against meningococcal groups A, C,W135 and Y, conjugated to tetanus toxoid, was authorised for use in the European Union, starting at age 1 year. The two tetravalent meningococcal conjugate vaccines have not been compared in head-to-head trials. Four immunogenicity studies compared the tetravalent conjugate vaccine Nimenrix with an unconjugated tetravalent meningococcal vaccine in children and adults aged 2 to 55 years. The results showed that Nimenrix was more immunogenic than the unconjugated vaccine. Two immunogenicity studies showed that Nimenrix was at least as immunogenic as monovalent (group C) meningococcal conjugate vaccines in children aged from 1 to 2 years and from 2 to 10 years. In one study, prior vaccination with an unconjugated tetravalent meningococcal vaccine had little impact on the immunogenicity of a booster dose of the conjugate vaccine Nimenrix. Concomitant administration with other vaccines does not affect the immunogenicity of Nimenrix. Nimenrix causes more frequent local and systemic adverse reactions than the unconjugated tetravalent meningococcal vaccine and monovalent group C meningococcal conjugate vaccines. In children over 2 years of age, Nimenrix has no advantages over Menveo for vaccination against meningococcal serogroups A, C, W135 andY. In contrast, between the ages of 1 and 2 years, Nimenrix is the only vaccine with established immunogenicity. In addition, it has an acceptable harm-benefit balance.

  19. Meningococcal conjugate vaccines policy update: booster dose recommendations.

    Science.gov (United States)

    2011-12-01

    The Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention and the American Academy of Pediatrics approved updated recommendations for the use of quadravalent (serogroups A, C, W-135, and Y) meningococcal conjugate vaccines (Menactra [Sanofi Pasteur, Swiftwater, PA] and Menveo [Novartis, Basel, Switzerland]) in adolescents and in people at persistent high risk of meningococcal disease. The recommendations supplement previous Advisory Committee on Immunization Practices and American Academy of Pediatrics recommendations for meningococcal vaccinations. Data were reviewed pertaining to immunogenicity in high-risk groups, bactericidal antibody persistence after immunization, current epidemiology of meningococcal disease, meningococcal conjugate vaccine effectiveness, and cost-effectiveness of different strategies for vaccination of adolescents. This review prompted the following recommendations: (1) adolescents should be routinely immunized at 11 through 12 years of age and given a booster dose at 16 years of age; (2) adolescents who received their first dose at age 13 through 15 years should receive a booster at age 16 through 18 years or up to 5 years after their first dose; (3) adolescents who receive their first dose of meningococcal conjugate vaccine at or after 16 years of age do not need a booster dose; (4) a 2-dose primary series should be administered 2 months apart for those who are at increased risk of invasive meningococcal disease because of persistent complement component (eg, C5-C9, properdin, factor H, or factor D) deficiency (9 months through 54 years of age) or functional or anatomic asplenia (2-54 years of age) and for adolescents with HIV infection; and (5) a booster dose should be given 3 years after the primary series if the primary 2-dose series was given from 2 through 6 years of age and every 5 years for persons whose 2-dose primary series or booster dose was given at 7 years of age or older who are at

  20. INTERNATIONAL EXPERIENCE OF ADMINISTRATION OF PNEUMOCOCCAL CONJUGATED VACCINES: PROBLEMS, PROGRESS, PERSPECTIVES

    OpenAIRE

    M.V. Fedoseenko; L. S. Namazova-Baranova

    2009-01-01

    This article presents the review of results of International conference on pneumococcal conjugated vaccines. Main results of international experience in the field of control of pneumococcal infection spreading are analyzed. Authors present modern data of clinical and economic effectiveness and safety of pneumococcal conjugated vaccine RCV-7, and describe experience of administration of vaccines of next generation – PCV-10 and PCV-13.Key words: children, pneumococcal infections, prophylaxis, v...

  1. Development and technology transfer of Haemophilus influenzae type b conjugate vaccines for developing countries.

    Science.gov (United States)

    Beurret, Michel; Hamidi, Ahd; Kreeftenberg, Hans

    2012-07-13

    This paper describes the development of a Haemophilus influenzae type b (Hib) conjugate vaccine at the National Institute for Public Health and the Environment/Netherlands Vaccine Institute (RIVM/NVI, Bilthoven, The Netherlands), and the subsequent transfer of its production process to manufacturers in developing countries. In 1998, at the outset of the project, the majority of the world's children were not immunized against Hib because of the high price and limited supply of the conjugate vaccines, due partly to the fact that local manufacturers in developing countries did not master the Hib conjugate production technology. To address this problem, the RIVM/NVI has developed a robust Hib conjugate vaccine production process based on a proven model, and transferred this technology to several partners in India, Indonesia, Korea and China. As a result, emerging manufacturers in developing countries acquired modern technologies previously unavailable to them. This has in turn facilitated their approach to producing other conjugate vaccines. As an additional spin-off from the project, a World Health Organization (WHO) Hib quality control (QC) course was designed and conducted at the RIVM/NVI, resulting in an increased regulatory capacity for conjugate vaccines in developing countries at the National Regulatory Authority (NRA) level. For the local populations, this has translated into an increased and sustainable supply of affordable Hib conjugate-containing combination vaccines. During the course of this project, developing countries have demonstrated their ability to produce large quantities of high-quality modern vaccines after a successful transfer of the technology.

  2. Forecasting invasive pneumococcal disease trends after the introduction of 13-valent pneumococcal conjugate vaccine in the United States, 2010-2020.

    Science.gov (United States)

    Link-Gelles, Ruth; Taylor, Thomas; Moore, Matthew R

    2013-05-24

    Pneumococcal vaccines are highly effective at preventing invasive pneumococcal disease (IPD), a leading cause of global morbidity. Because pneumococcal vaccines can be expensive, it is useful to estimate what impact might be expected from their introduction. Our objective was to develop a statistical model that could predict rates of IPD following introduction of 13-valent pneumococcal conjugate vaccine (PCV13) in the U.S. We used active surveillance data to design and validate a Poisson model forecasting the reductions in IPD observed after U.S. introduction of 7-valent pneumococcal conjugate vaccine (PCV7) in 2000. We used this model to forecast rates of IPD from 2010 to 2020 in the presence of PCV13. Because increases in non-PCV7-type IPD were evident following PCV7 introduction, we evaluated varying levels of increase in non-PCV13-type IPD ("serotype replacement") by sensitivity analyses. A total of 43,507 cases of IPD were identified during 1998-2009; cases from this period were used to develop the model, which accurately predicted indirect effects of PCV7 in adults, as well as serotype replacement. Assuming that PCV13 provides similar protection against PCV13 serotypes as PCV7 did against PCV7 serotypes, the base-case model predicted approximately 168,000 cases of IPD prevented from 2011 to 2020. When serotype replacement was varied in sensitivity analyses from 0 to levels comparable to that seen with serotype 19A (the most common replacement serotype since PCV7 was introduced), the model predicted 167,000-170,000 cases prevented. The base-case model predicted rates of IPD in children under five years of age decreasing from 21.9 to 9.3 cases per 100,000 population. This model provides a "benchmark" for assessing progress in the prevention of IPD in the years after PCV13 introduction. The amount of serotype replacement is unlikely to greatly affect the overall number of cases prevented by PCV13. Published by Elsevier Ltd.

  3. Cost-effectiveness models of pneumococcal conjugate vaccines : Variability and impact of modeling assumptions

    NARCIS (Netherlands)

    Farkouh, Raymond A; Klok, Rogier M; Postma, Maarten J; Roberts, Craig S; Strutton, David R

    2012-01-01

    Currently, 13-valent pneumococcal conjugate vaccine (PCV); and ten-valent PCV vaccine are marketed. Neither vaccine obtained regulatory approval based on efficacy trials, but instead were approved based on a surrogate end point: immunogenicity data measuring effective antibody levels. Therefore, dir

  4. Nasopharyngeal Pneumococcal Colonization among Children after Pneumococcal Conjugate Vaccine Introduction

    Directory of Open Access Journals (Sweden)

    Manoochehr Karami

    2017-08-01

    Full Text Available World Health Organization has recommended all countries to introduction of Pneumococcal Conjugate Vaccine (PCV in routine immunization schedule, especially those countries with higher rate of mortality in children. However, Islamic Republic of Iran and more than 50 other countries including Algeria, Antigua and Barbuda, Belarus, Belize, Bhutan, Bosnia and Herzegovina, Brunei Darussalam, Cabo Verde, Chad, China, Comoros, Cook Islands, Croatia, Cuba, Czech Republic, Democratic People's Republic of Korea, Dominica, Egypt, Equatorial Guinea, Estonia, Gabon, Grenada, Guinea, Haiti, India, Jamaica, Jordan, Malaysia, Maldives, Malta, Montenegro, Nauru, Poland, Romania, Saint Kitts and Nevis, Saint Lucia, Saint Vincent and the Grenadines, Samoa, San Marino, Serbia, Seychelles, Slovenia, Somalia, South Sudan, Sri Lanka, Syrian Arab Republic, Tajikistan, Thailand, The former Yugoslav Republic of Macedonia, Timor-Leste, Tonga, Tunisia, Turkmenistan, Tuvalu, Ukraine, Vanuatu, and Viet Namhave not introduced PCV till April 2016.

  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. Vaccination with 10-valent pneumococcal conjugate vaccine in infants according to HIV status

    Science.gov (United States)

    Madhi, Shabir A.; Koen, Anthonet; Jose, Lisa; van Niekerk, Nadia; Adrian, Peter V.; Cutland, Clare; François, Nancy; Ruiz-Guiñazú, Javier; Yarzabal, Juan-Pablo; Moreira, Marta; Borys, Dorota; Schuerman, Lode

    2017-01-01

    Abstract Background: Phase III, open-label, single-center, controlled study in South Africa (ClinicalTrials.gov: NCT00829010) to evaluate immunogenicity, reactogenicity, and safety of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in human immunodeficiency virus (HIV)-infected (HIV+), HIV-exposed-uninfected (HEU), and HIV-unexposed-uninfected (HUU) children. Methods: Children stratified by HIV status received PHiD-CV primary vaccination (age 6/10/14 weeks; coadministered with routine childhood vaccines) and booster dose (age 9–10 months). Immune responses, assessed using enzyme-linked immunosorbent and functional assays, and safety were evaluated up to 14 months post-booster. Results: Of 83, 101, and 100 children enrolled in HIV+, HEU, and HUU groups, 70, 91, and 93 were included in according-to-protocol immunogenicity cohort. For each vaccine-serotype, percentages of children with antibody concentrations ≥0.2 μg/mL were ≥97% 1 month post-primary vaccination and ≥98.5% 1 month post-booster (except for 6B and 23F at both timepoints). Post-primary vaccination, functional antibody responses were lower in HIV+ children: for each vaccine-serotype, percentages of children with opsonophagocytic activity (OPA) titres ≥8 were ≥72%, ≥81%, and ≥79% for HIV+, HEU, and HUU children. Post-booster, ≥87% of children in each group had OPA titres ≥8. Reactogenicity was similar across groups. Thirty one (37%) HIV+, 25 (25%) HEU, and 20 (20%) HUU children reported ≥1 serious adverse event. Five HIV+ and 4 HEU children died. One death (sudden infant death syndrome; HEU group; 3 days post-dose 1) was considered potentially vaccine-related. Conclusion: PHiD-CV was immunogenic and well-tolerated in HIV+, HEU, and HUU children, and has the potential to provide substantial benefit irrespective of HIV infection status. PMID:28079828

  7. Vaccination with 10-valent pneumococcal conjugate vaccine in infants according to HIV status.

    Science.gov (United States)

    Madhi, Shabir A; Koen, Anthonet; Jose, Lisa; van Niekerk, Nadia; Adrian, Peter V; Cutland, Clare; François, Nancy; Ruiz-Guiñazú, Javier; Yarzabal, Juan-Pablo; Moreira, Marta; Borys, Dorota; Schuerman, Lode

    2017-01-01

    Phase III, open-label, single-center, controlled study in South Africa (ClinicalTrials.gov: NCT00829010) to evaluate immunogenicity, reactogenicity, and safety of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in human immunodeficiency virus (HIV)-infected (HIV+), HIV-exposed-uninfected (HEU), and HIV-unexposed-uninfected (HUU) children. Children stratified by HIV status received PHiD-CV primary vaccination (age 6/10/14 weeks; coadministered with routine childhood vaccines) and booster dose (age 9-10 months). Immune responses, assessed using enzyme-linked immunosorbent and functional assays, and safety were evaluated up to 14 months post-booster. Of 83, 101, and 100 children enrolled in HIV+, HEU, and HUU groups, 70, 91, and 93 were included in according-to-protocol immunogenicity cohort. For each vaccine-serotype, percentages of children with antibody concentrations ≥0.2 μg/mL were ≥97% 1 month post-primary vaccination and ≥98.5% 1 month post-booster (except for 6B and 23F at both timepoints). Post-primary vaccination, functional antibody responses were lower in HIV+ children: for each vaccine-serotype, percentages of children with opsonophagocytic activity (OPA) titres ≥8 were ≥72%, ≥81%, and ≥79% for HIV+, HEU, and HUU children. Post-booster, ≥87% of children in each group had OPA titres ≥8. Reactogenicity was similar across groups. Thirty one (37%) HIV+, 25 (25%) HEU, and 20 (20%) HUU children reported ≥1 serious adverse event. Five HIV+ and 4 HEU children died. One death (sudden infant death syndrome; HEU group; 3 days post-dose 1) was considered potentially vaccine-related. PHiD-CV was immunogenic and well-tolerated in HIV+, HEU, and HUU children, and has the potential to provide substantial benefit irrespective of HIV infection status.

  8. Sinusitis and pneumonia hospitalization after introduction of pneumococcal conjugate vaccine.

    Science.gov (United States)

    Lindstrand, Ann; Bennet, Rutger; Galanis, Ilias; Blennow, Margareta; Ask, Lina Schollin; Dennison, Sofia Hultman; Rinder, Malin Ryd; Eriksson, Margareta; Henriques-Normark, Birgitta; Ortqvist, Ake; Alfvén, Tobias

    2014-12-01

    Streptococcus pneumoniae is a major cause of pneumonia and sinusitis. Pneumonia kills >1 million children annually, and sinusitis is a potentially serious pediatric disease that increases the risk of orbital and intracranial complications. Although pneumococcal conjugate vaccine (PCV) is effective against invasive pneumococcal disease, its effectiveness against pneumonia is less consistent, and its effect on sinusitis is not known. We compared hospitalization rates due to sinusitis, pneumonia, and empyema before and after sequential introduction of PCV7 and PCV13. All children 0 to sinusitis, pneumonia, or empyema in Stockholm County, Sweden, from 2003 to 2012 were included in a population-based study of hospital registry data on hospitalizations due to sinusitis, pneumonia, or empyema. Trend analysis, incidence rates, and rate ratios (RRs) were calculated comparing July 2003 to June 2007 with July 2008 to June 2012, excluding the year of PCV7 introduction. Hospitalizations for sinusitis decreased significantly in children aged 0 to sinusitis and pneumonia in children aged 0 to sinusitis and 19% lower risk of hospitalization for pneumonia in children aged 0 to <2 years, in a comparison of 4 years before and 4 years after vaccine introduction. Copyright © 2014 by the American Academy of Pediatrics.

  9. Antibiotic resistance and serotype distribution of invasive pneumococcal diseases before and after introduction of pneumococcal conjugate vaccine in the Kingdom of Saudi Arabia (KSA).

    Science.gov (United States)

    Shibl, Atef M; Memish, Ziad A; Al-Kattan, Khaled M

    2012-12-31

    Streptococcus pneumoniae is one of the most common bacterial causes of morbidity and mortality worldwide, causing life threatening infections such as meningitis, pneumonia and febrile bacteremia, particular among young children. The severity and frequency of S. pneumoniae infection and emergence of drug-resistant isolates have highlighted the need for prevention of invasive pneumococcal disease (IPD) as the best method for controlling disease; to better achieve this, more information is needed about serotype distribution and patterns of antibiotic resistance in children in the Kingdom of Saudi Arabia (KSA). Cases of pneumococcal infections in children aged antibiotic susceptibility. This covers the time period just before limited introduction of 7-valent pneumococcal conjugate vaccine (PCV7) in 2006, to its introduction into the national immunization program in 2008, until right after a switch to PCV13 in 2010. Case definition required isolation of S. pneumoniae from blood, cerebrospinal fluid, or any sterile biological fluid. Isolates from 311 eligible cases were collected from different regions across KSA, 250 from blood and 61 from cerebrospinal fluid. The most frequently isolated IPD serotypes were 23F, 19F, 6B, 5 and 1. Over the course of the study, there was significant rise of serotype 19A (covered by PCV13 but not PCV7), which accounted for 20% of isolates of IPD in Western and 5% in Central regions in the last 2 years in KSA. There was a notable decrease in serotype 18C over this period, one of the PCV7 serotypes. Serotype coverage for PCV7, PCV10, PCV13 in children resistant, and 62% were erythromycin-resistant. Continued surveillance is critical to measure the emerging of new serotypes and antibiotic resistance strain, and the potential impact of new PCVs. PCV13, recently introduced into the national immunization schedule in place of PCV7, provides the widest coverage among all IPD serotypes across KSA.

  10. 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

  11. Mycobacterial cell-wall skeleton as a universal vaccine vehicle for antigen conjugation.

    Science.gov (United States)

    Paik, Tae-Hyun; Lee, Ji-Sook; Kim, Ki-Hye; Yang, Chul-Su; Jo, Eun-Kyeong; Song, Chang-Hwa

    2010-11-23

    Mycobacterial cell-wall skeleton (CWS) is an immunoactive and biodegradable particulate adjuvant and has been used for immunotherapy in patients with cancer. The CWS of Mycobacterium bovis bacillus Calmette-Guérin (BCG-CWS) was studied as a universal vaccine vehicle for antigen conjugation, to develop potentially effective and safe vaccines. Here, we describe experiments in which protein antigens, such as keyhole limpet haemocyanin (KLH), ovalbumin (OVA) and bovine serum albumin (BSA) were highly efficiently coupled to 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide (EDC/NHS)-activated carboxyl groups of BCG-CWS, and tested the immunogenicity of OVA-conjugated BCG-CWS vaccine. We found that a strong immune response was induced in mice immunised with OVA-conjugated BCG-CWS, which was similar to the enhancement of the immune responses in mice immunised with OVA and complete Freund's adjuvant. Covalent conjugation of OVA to BCG-CWS was essential for Th1-skewed immune responses, with prominent expression of IFN-γ. Furthermore, antigen-conjugated BCG-CWS vaccine is simple to manufacture, safe, and easy to use. Our results suggest that mycobacterial CWS as a universal vaccine vehicle for conjugation of a wide variety of antigens constitutes a breakthrough for development of the most promising vaccines for infections, allergic diseases, and cancer.

  12. 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 OBJECTIVE: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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

  13. Meningococcal Serogroup A, C, W-135 and Y Conjugated Vaccine : A Cost-Effectiveness Analysis in the Netherlands

    NARCIS (Netherlands)

    Hepkema, Hiltsje; Pouwels, Koen B.; 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,W-135, Y meningococcal conjugate vaccine (MenACWY) was licens

  14. 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.

  15. 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.

  16. 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 polysaccharid

  17. Preparation and testing of a Haemophilus influenzae Type b/Hepatitis B surface antigen conjugate vaccine.

    Science.gov (United States)

    An, So Jung; Woo, Joo Sung; Chae, Myung Hwa; Kothari, Sudeep; Carbis, Rodney

    2015-03-24

    The majority of conjugate vaccines focus on inducing an antibody response to the polysaccharide antigen and the carrier protein is present primarily to induce a T-cell dependent response. In this study conjugates consisting of poly(ribosylribitolphosphate) (PRP) purified from Haemophilus influenzae Type b bound to Hepatitis B virus surface antigen (HBsAg) virus like particles were prepared with the aim of inducing an antibody response to not only the PRP but also the HBsAg. A conjugate consisting of PRP bound to HBsAg via an adipic acid dihydrazide (ADH) spacer induced strong IgG antibodies to both the PRP and HBsAg. When conjugation was performed without the ADH spacer the induction of an anti-PRP response was equivalent to that seen by conjugate with the ADH spacer, however, a negligible anti-HBsAg response was induced. For comparison, PRP was conjugated to diphtheria toxoid (DT) and Vi polysaccharide purified from Salmonella Typhi conjugated to HBsAg both using an ADH spacer. The PRPAH-DT conjugate induced strong anti-PRP and anti-DT responses, the Vi-AHHBsAg conjugate induced a good anti-HBsAg response but not as strong as that induced by the PRPAH-HBsAg conjugate. This study demonstrated that in mice it was possible to induce robust antibody responses to both polysaccharide and carrier protein provided the conjugate has certain physico-chemical properties. A PRPAH-HBsAg conjugate with the capacity to induce anti-PRP and anti-HBsAg responses could be incorporated into a multivalent pediatric vaccine and simplify formulation of such a vaccine.

  18. [Subunit vaccines--antigens, carriers, conjugation methods and the role of adjuvants].

    Science.gov (United States)

    Jarząb, Anna; Skowicki, Michał; Witkowska, Danuta

    2013-11-27

    Vaccines are effective tools protecting against the development of infectious diseases caused by pathogenic microorganisms. Currently, we have vaccines protecting against many infections, where standard therapy is not only difficult but often impossible due to the ever-progressive increase in bacterial resistance to many available antibiotics. Among vaccines which have been used in the prevention of infection are the traditional vaccines containing live, killed or attenuated strains of microorganisms. However, it should be noted that such vaccines are not always effective, especially when the expected immune response is directed against specific antigens. Subunit vaccines belong to new generation vaccines and have gained more and more interest in recent years. These vaccines contain fragments of pathogenic microorganisms, which are highly purified and immunogenic antigens. Using these purified antigens excludes the risk of post-vaccination infection. In addition, subunit vaccines minimize side-effects associated with the use of whole bacterial cells. The paper discusses the most promising and the most tested antigens, vaccine carriers, conjugation methods and vaccine delivery systems which are being used in the design of subunit vaccines. This paper also highlights the advantages and disadvantages of adjuvants, which are substances to support the immune response in humans, and the relationship between adjuvants' efficacy and their mechanism of action.

  19. 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...

  20. Comparative assessment of immunization coverage of migrant children between national immunization program vaccines and non-national immunization program vaccines in East China.

    Science.gov (United States)

    Hu, Yu; Luo, Shuying; Tang, Xuewen; Lou, Linqiao; Chen, Yaping; Guo, Jing

    2015-01-01

    This study aimed to describe the disparities in immunization coverage between National Immunization Program (NIP) vaccines and non-NIP vaccines in Yiwu and to identify potential determinants. A face-to-face interview-based questionnaire survey among 423 migrant children born from 1 June 2010 to 31 May 2013 was conducted. Immunization coverage was estimated according to the vaccines scheduled at different age, the birth cohorts, and socio- demographic characteristics. Single-level logistic regression analysis was applied to identify the determinants of coverage of non-NIP vaccines. We found that NIP vaccines recorded higher immunization coverage compared with non-NIP vaccines (87.9100%- vs 0%-74.8%). Among the non-NIP vaccines, varicella vaccine (VarV) recorded the highest coverage of 85.4%, which was introduced in 1998; while 7-valent pneumococcal conjugate vaccine(PCV7) recorded the lowest coverage of 0% for primary series, which was introduced recently. Lower coverage rate of non-NIP vaccines was significantly associated with more siblings in household, shorter duration of living in the surveyed areas, lower family income, mother with a job, mother with poor awareness of vaccination, and mother with lower education level. We found the immunization coverage rate of non-NIP vaccines was significant lower than that of NIP vaccines. Expansion of NIP to include non-NIP vaccines can provide better protection against the vaccine preventable diseases through increased immunization coverage.

  1. Chemical conjugate TMV-peptide bivalent fusion vaccines improve cellular immunity and tumor protection.

    Science.gov (United States)

    McCormick, Alison A; Corbo, Tina A; Wykoff-Clary, Sherri; Palmer, Kenneth E; Pogue, Gregory P

    2006-01-01

    Chemical conjugation of CTL peptides to tobacco mosaic virus (TMV) has shown promise as a molecular adjuvant scaffold for augmentation of cellular immune responses to peptide vaccines. This study demonstrates the ease of generating complex multipeptide vaccine formulations using chemical conjugation to TMV for improved vaccine efficacy. We have tested a model foreign antigen target-the chicken ovalbumin-derived CTL peptide (Ova peptide), as well as mouse melanoma-associated CTL epitopes p15e and tyrosinase-related protein 2 (Trp2) peptides that are self-antigen targets. Ova peptide fusions to TMV, as bivalent formulations with peptides encoding additional T-help or cellular uptake via the integrin-receptor binding RGD peptide, showed improved vaccine potency evidenced by significantly enhanced numbers of antigen-reactive T cells measured by in vitro IFNgamma cellular analysis. We measured the biologically relevant outcome of vaccination in protection of mice from EG.7-Ova tumor challenge, which was achieved with only two doses of vaccine ( approximately 600 ng peptide) given without adjuvant. The p15e peptide alone or Trp2 peptide alone, or as a bivalent formulation with T-help or RGD uptake epitopes, was unable to stimulate effective tumor protection. However, a vaccine with both CTL peptides fused together onto TMV generated significantly improved survival. Interestingly, different bivalent vaccine formulations were required to improve vaccine efficacy for Ova or melanoma tumor model systems.

  2. Cost-effectiveness of adult pneumococcal conjugate vaccination in the Netherlands.

    Science.gov (United States)

    Mangen, Marie-Josée J; Rozenbaum, Mark H; Huijts, Susanne M; van Werkhoven, Cornelis H; Postma, Douwe F; Atwood, Mark; van Deursen, Anna M M; van der Ende, Arie; Grobbee, Diederick E; Sanders, Elisabeth A M; Sato, Reiko; Verheij, Theo J M; Vissink, Conrad E; Bonten, Marc J M; de Wit, G Ardine

    2015-11-01

    The Community-Acquired Pneumonia Immunization Trial in Adults (CAPiTA) demonstrated the efficacy of 13-valent pneumococcal conjugate vaccine (PCV13) in preventing vaccine-type community-acquired pneumonia and vaccine-type invasive pneumococcal disease in elderly subjects. We examined the cost-effectiveness of PCV13 vaccination in the Netherlands. Using a Markov-type model, incremental cost-effectiveness ratios (ICER) of PCV13 vaccination in different age- and risk-groups for pneumococcal disease were evaluated using a societal perspective. Estimates of quality-adjusted life-years (QALYs), costs, vaccine efficacy and epidemiological data were based on the CAPiTA study and other prospective studies. The base-case was PCV13 vaccination of adults aged 65-74 years compared to no vaccination, assuming no net indirect effects in base-case due to paediatric 10-valent pneumococcal conjugate vaccine use. Analyses for age- and risk-group specific vaccination strategies and for different levels of hypothetical herd effects from a paediatric PCV programme were also conducted. The ICER for base-case was €8650 per QALY (95% CI 5750-17,100). Vaccination of high-risk individuals aged 65-74 years was cost-saving and extension to medium-risk individuals aged 65-74 years yielded an ICER of €2900. Further extension to include medium- and high-risk individuals aged ≥18 years yielded an ICER of €3100.PCV13 vaccination is highly cost-effective in the Netherlands. The transferability of our results to other countries depends upon vaccination strategies already implemented in those countries.

  3. 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.

  4. 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.

  5. Safety of Quadrivalent Meningococcal Conjugate Vaccine in 11- to 21-Year-Olds.

    Science.gov (United States)

    Tseng, Hung-Fu; Sy, Lina S; Ackerson, Bradley K; Hechter, Rulin C; Tartof, Sara Y; Haag, Mendel; Slezak, Jeffrey M; Luo, Yi; Fischetti, Christine A; Takhar, Harp S; Miao, Yan; Cunnington, Marianne; Solano, Zendi; Jacobsen, Steven J

    2017-01-01

    Meningococcal conjugate vaccination is recommended in the United States. This study evaluates the safety of quadrivalent meningococcal conjugate vaccine in a cohort aged 11 to 21 years. This cohort study with self-controlled case-series analysis was conducted at Kaiser Permanente Southern California. Individuals receiving MenACWY-CRM, a quadrivalent meningococcal conjugate vaccine, during September 30, 2011 to June 30, 2013, were included. Twenty-six prespecified events of interest (EOIs), including neurologic, rheumatologic, hematologic, endocrine, renal, pediatric, and pediatric infectious disease EOIs, were identified through electronic health records 1 year after vaccination. Of these, 16 were reviewed by case review committees. Specific risk and comparison windows after vaccination were predefined for each EOI. The relative incidence (RI) and 95% confidence intervals (CIs) were estimated through conditional Poisson regression models, adjusted for seasonality. This study included 48 899 vaccinated individuals. No cases were observed in the risk window for 14 of 26 EOIs. The RI for Bell's palsy, a case review committee-reviewed EOI, was statistically significant (adjusted RI: 2.9, 95% CI: 1.1-7.5). Stratified analyses demonstrated an increased risk for Bell's palsy in subjects receiving concomitant vaccines (RI = 5.0, 95% CI = 1.4-17.8), and no increased risk for those without concomitant vaccine (RI = 1.1, 95% CI = 0.2-5.5). We observed a temporal association between occurrence of Bell's palsy and receipt of MenACWY-CRM concomitantly with other vaccines. The association needs further investigation as it could be due to chance, concomitant vaccination, or underlying medical history predisposing to Bell's palsy. Copyright © 2017 by the American Academy of Pediatrics.

  6. Preparation and Evaluation of a New Lipopolysaccharide-based Conjugate as a Vaccine Candidate for Brucellosis.

    Science.gov (United States)

    Siadat, Seyed Davar; Vaziri, Farzam; Eftekhary, Mamak; Karbasian, Maryam; Moshiri, Arfa; Aghasadeghi, Mohammad R; Ardestani, Mehdi S; Alitappeh, Meghdad Abdollahpour; Arsang, Amin; Fateh, Abolfazl; Peerayeh, Shahin Najar; Bahrmand, Ahmad R

    2015-02-01

    Development of an efficacious vaccine against brucellosis has been a challenge for scientists for many years. At present, there is no licensed vaccine against human brucellosis. To overcome this problem, currently, antigenic determinants of Brucella cell wall such as Lipopolysaccharide (LPS) are considered as potential candidates to develop subunit vaccines. In this study, Brucella abortus LPS was used for conjugation to Neisseria meningitidis serogroup B outer membrane vesicle (OMV) as carrier protein using carbodiimide and adipic acid-mediated coupling and linking, respectively. Groups of eight BALB/c mice were injected subcutaneously with 10 μg LPS alone, combined LPS + OMV and conjugated LPS-OMV on 0 days, 14 days, 28 days and 42 days. Anti-LPS IgG was measured in serum. The yield of LPS to OMV in LPS-OMV conjugate was 46.55%, on the basis of carbohydrate content. The ratio for LPS to OMV was 4.07. The LPS-OMV conjugate was the most immunogenic compound that stimulated following the first injection with increased IgG titer of ∼5-fold and ∼1.3-fold higher than that produced against LPS and LPS in noncovalent complex to OMV (LPS + OMV), respectively. The highest anti-LPS IgG titer was detected 2 weeks after the third injection (Day 42) of LPS-OMV conjugate. The conjugated compound elicited higher titers of IgG than LPS + OMV, that showed a 100-120-fold rise of anti-LPS IgG in mice. These results indicate that our conjugated LPS-OMV can be used as a brucellosis vaccine, but further investigation is required.

  7. Effect of vaccination with carrier protein on response to meningococcal C conjugate vaccines and value of different immunoassays as predictors of protection.

    Science.gov (United States)

    Burrage, Moya; Robinson, Andrew; Borrow, Ray; Andrews, Nick; Southern, Joanna; Findlow, Jamie; Martin, Sarah; Thornton, Carol; Goldblatt, David; Corbel, Michael; Sesardic, Dorothea; Cartwight, Keith; Richmond, Peter; Miller, Elizabeth

    2002-09-01

    In order to plan for the wide-scale introduction of meningococcal C conjugate (MCC) vaccine for United Kingdom children up to 18 years old, phase II trials were undertaken to investigate whether there was any interaction between MCC vaccines conjugated to tetanus toxoid (TT) or a derivative of diphtheria toxin (CRM(197)) and diphtheria-tetanus vaccines given for boosting at school entry or leaving. Children (n = 1,766) received a diphtheria-tetanus booster either 1 month before, 1 month after, or concurrently with one of three MCC vaccines conjugated to CRM(197) or TT. All of the MCC vaccines induced high antibody responses to the serogroup C polysaccharide that were indicative of protection. The immune response to the MCC-TT vaccine was reduced as a result of prior immunization with a tetanus-containing vaccine, but antibody levels were still well above the lower threshold for protection. Prior or simultaneous administration of a diphtheria-containing vaccine did not affect the response to MCC-CRM(197) vaccines. The immune responses to the carrier proteins were similar to those induced by a comparable dose of diphtheria or tetanus vaccine. The results also demonstrate that, for these conjugate vaccines in these age groups, both standard enzyme-linked immunosorbent assays and those that measure high-avidity antibodies to meningococcal C polysaccharide correlated equally well with assays that measure serum bactericidal antibodies, the established serological correlate of protection for MCC vaccines.

  8. 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.

  9. Pneumonia Prevention during a Humanitarian Emergency: Cost-effectiveness of Haemophilus Influenzae Type B Conjugate Vaccine and Pneumococcal Conjugate Vaccine in Somalia.

    Science.gov (United States)

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

    2015-08-01

    Pneumonia is a leading cause of death among children less than five years old during humanitarian emergencies. Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae are the leading causes of bacterial pneumonia. Vaccines for both of these pathogens are available to prevent pneumonia. Problem This study describes an economic analysis from a publicly funded health care system perspective performed on a birth cohort in Somalia, a country that has experienced a protracted humanitarian emergency. An impact and cost-effectiveness analysis was performed comparing: no vaccine, Hib vaccine only, pneumococcal conjugate vaccine 10 (PCV10) only, and both together administered through supplemental immunization activities (SIAs). The main summary measure was the incremental cost per disability-adjusted life-years (DALYs) averted. One-way sensitivity analysis was conducted for uncertainty in parameter values. Each SIA would avert a substantial number of cases and deaths. Compared with no vaccine, the DALYs averted by two SIAs for two doses of Hib vaccine was US $202.93 (lower and upper limits: $121.80-$623.52), two doses of PCV10 was US $161.51 ($107.24-$227.21), and two doses of both vaccines was US $152.42 ($101.20-$214.42). Variables that influenced the cost-effectiveness for each strategy most substantially were vaccine effectiveness, case fatality rates (CFRs), and disease burden. The World Health Organization (WHO) defines a cost-effective intervention as costing one to three times the per capita gross domestic product (GDP; in 2011, for Somalia=US $112). Based on the presented model, Hib vaccine alone, PCV10 alone, or Hib vaccine and PCV10 given together in SIAs are cost-effective interventions in Somalia. The WHO/Strategic Advisory Group of Experts decision-making factors for vaccine deployment appear to have all been met: the disease burden is large, the vaccine-related risk is low, prevention in this setting is more feasible than treatment, the vaccine

  10. Immunological evaluation of an alginate-based conjugate as a vaccine candidate against Pseudomonas aeruginosa.

    Science.gov (United States)

    Farjah, Ali; Owlia, Parviz; Siadat, Seyed Davar; Mousavi, Seyed Fazlollah; Ardestani, Mehdi Shafiee; Mohammadpour, Hashem Khorsand

    2015-02-01

    Pseudomonas aeruginosa is an opportunistic pathogen that causes serious infections, is usually resistant to antimicrobial agents, and is the leading cause of morbidity and premature mortality in patients with cystic fibrosis (CF). Mucoid strains of P. aeruginosa produce a virulence factor known as alginate. Developing a strategy to raise opsonic antibodies against alginate could be promising for the treatment of P. aeruginosa infection in CF patients. Conjugation of alginate to a carrier protein is a good method for increasing the immunogenicity of alginate. We conjugated alginate to the outer membrane vesicle (OMV) of Neisseria meningitidis serogroup B, which is a safe carrier protein, and evaluated its efficacy in mice. To evaluate the immune response, total IgG, IgG1, IgG2a, and IgG2b titers were analyzed. Immunization of mice with the alginate-OMV conjugate raised the levels of opsonic antibodies, and the vaccinated mice were protected when challenged intranasally with P. aeruginosa. Further studies showed that the conjugated vaccine could eliminate P. aeruginosa from the lungs of infected mice. This study supports the proposal that immunization of mice with an alginate-OMV conjugate vaccine could be safe and protective against P. aeruginosa infection.

  11. 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...

  12. Preparation and immunogenicity-evaluation of typhoid O-specific polysaccharides bio-conjugate vaccines.

    Science.gov (United States)

    Zhehui, Peng; Chao, Pan; Peng, Sun; Erling, Feng; Jun, Wu; Li, Zhu; Qingzhong, Peng; Hengliang, Wang

    2015-05-01

    Typhoid fever caused by Salmonella Typhi is still a major public health problem in developing countries. In this study, we constructed a genetically modified Salmonella Typhi strain expressing O-specific polysaccharides (OPS) antigen conjugated to a carrier, recombinant Pseudomonas aeruginosa exotoxin A(rEPA N29). The conjugates (OPS-rEPA N29) were further purified and evaluated for their immunogenicity. The results of ELISA showed that the conjugates evoked higher titers of IgG than OPS, suggesting that rEPAN29 increased immunogenicity of OPS significantly as a carrier. Moreover, three injections with 3-week interval evoked slightly higher titers of IgG than three injections with 2-week interval. However, injection of excess conjugates could not evoke higher titers of IgG against lipid polysaccharide (LPS). In summary, our study provides a new strategy for preparing polysaccharides-protein conjugate vaccines as well as similar bio-conjugate vaccines of other Gram-negative pathogens.

  13. Impact of 13-Valent Pneumococcal Conjugate Vaccination in Invasive Pneumococcal Disease Incidence and Mortality

    DEFF Research Database (Denmark)

    Harboe, Zitta Barrella; Dalby, Tine; Weinberger, Daniel M

    2014-01-01

    or expected as a part of natural, cyclical variations. METHODS: This was a Danish nationwide population-based cohort study based on the linkage of laboratory surveillance data and the Danish Civil Registration System. Changes in IPD incidence and mortality during baseline (2000-2007), 7-valent pneumococcal...

  14. What do we know about the cost-effectiveness of pneumococcal conjugate vaccination in older adults?

    Science.gov (United States)

    Newall, A T

    2016-10-02

    The cost-effectiveness of 13-type pneumococcal conjugate vaccine (PCV13) use in older adults, and the relative merits when compared to the 23-type polysaccharide pneumococcal vaccine (PPV23), has been a topic of much debate. Although a number of economics evaluations have been conducted many of these were completed before the availability of critical data on PCV13 efficacy in older adults. Recent studies using this data have found conflicting results. This may in part reflect differences in the level of herd protection from infant pneumococcal vaccination programs in different countries. The costs and benefits of pneumococcal vaccination in adults are likely to rest on several critical parameters: the magnitude pneumococcal disease in older adults and the serotypes responsible for it, the efficacy of each vaccine against invasive and non-invasive pneumonia, the duration of vaccine protection, and differences in vaccine price. The ongoing changes in pneumococcal disease patterns highlight the need for economic evaluations to use recent serotype-specific disease estimates from the setting under consideration. In countries that do recommend PCV13 use in adults, post-implementation economic evaluation (using data from after a program is implemented) may be useful to help inform potential future changes to vaccine recommendations as well as the maximum price that should be paid for the vaccines in future negotiations.

  15. 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.

  16. 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-specific a......The human B-lymphocyte response to protein-conjugated polysaccharide antigens has not previously been studied at the cellular level. In order to do so, we developed and evaluated haemolytic plaque-forming cell assays detecting Haemophilus influenzae type b (Hib) capsular polysaccharide...... 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...

  17. Preclinical immunogenicity and functional activity studies of an A+W meningococcal outer membrane vesicle (OMV) vaccine and comparisons with existing meningococcal conjugate- and polysaccharide vaccines.

    Science.gov (United States)

    Tunheim, G; Arnemo, M; Næss, L M; Fjeldheim, Å K; Nome, L; Bolstad, K; Aase, A; Mandiarote, A; González, H; González, D; García, L; Cardoso, D; Norheim, G; Rosenqvist, E

    2013-12-09

    Meningococci of serogroups A and W (MenA and MenW) are the main causes of epidemic bacterial meningitis outbreaks in sub-Saharan Africa. In this study we prepared a detergent extracted outer membrane vesicle (dOMV) vaccine from representative African MenA and MenW strains, and compared the immunogenicity of this vaccine with existing meningococcal conjugate and polysaccharide (PS) vaccines in mice. NMRI mice were immunized with preclinical batches of the A+W dOMV vaccine, or with commercially available vaccines; a MenA conjugate vaccine (MenAfriVac(®), Serum Institute of India), ACYW conjugate vaccine (Menveo(®), Novartis) or ACYW PS vaccine (Mencevax(®), GlaxoSmithKline). The mice received 2 doses of 1/10 or 1/50 of a human dose with a three week interval. Immune responses were tested in ELISA, serum bactericidal activity (SBA) and opsonophagocytic activity (OPA) assays. High levels of IgG antibodies against both A and W dOMV were detected in mice receiving the A+W dOMV vaccine. High SBA titers against both MenA and MenW vaccine strains were detected after only one dose of the A+W dOMV vaccine, and the titers were further increased after the second dose. The SBA and OPA titers in mice immunized with dOMV vaccine were significantly higher than in mice immunized with the ACYW-conjugate vaccine or the PS vaccine. Furthermore, the A+W dOMV vaccine was shown to induce SBA and OPA titers against MenA of the same magnitude as the titers induced by the A-conjugate vaccine. In conclusion, the A+W dOMV vaccine induced high levels of functional antibodies to both MenA and MenW strains, levels that were shown to be higher or equal to the levels induced by licensed meningococcal vaccines. Thus, an A+W dOMV vaccine could potentially serve as an alternative or a supplement to existing conjugate and PS vaccines in the African meningitis belt. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. 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.

  19. Pediatricians' perspectives on pneumococcal conjugate vaccines: An exploratory study in the private sector.

    Science.gov (United States)

    Zodpey, Sanjay; Farooqui, Habib Hasan; Chokshi, Maulik; Kumar, Balu Ravi; Thacker, Naveen

    2015-01-01

    There is a lack of information on supply-side determinants, their utilization, and the access to pneumococcal vaccination in India. The objective of this exploratory study was to document the perceptions and perspectives of practicing pediatricians with regard to pneumococcal conjugate vaccines (PCVs) in selected metropolitan areas of India. A qualitative study was conducted to generate evidence on the perspective of pediatricians practicing in the private sector regarding pneumococcal vaccination. The pediatricians were identified from 11 metropolitan areas on the basis of PCV vaccine sales in India through multilevel stratified sampling method. Relevant information was collected through in-depth personal interviews. Finally, qualitative data analysis was carried out through standard techniques such as the identification of key domains, words, phrases, and concepts from the respondents. We observed that the majority (67.7%) of the pediatricians recommended pneumococcal vaccination to their clients, whereas 32.2% recommended it to only those who could afford it. More than half (62.9%) of the pediatricians had no preference for any brand and recommended both a 10-valent pneumococcal conjugate vaccine (PCV10) and a 13-valent PCV (PCV13), whereas 8.0% recommended none. An overwhelming majority (97.3%) of the pediatricians reported that the main reason for a patient not following the pediatrician's advice for pneumococcal vaccination was the price of PCV. To reduce childhood pneumonia-related burden and mortality, pediatricians should use every opportunity to increase awareness about vaccine-preventable diseases, especially vaccine-preventable childhood pneumonia among their patients.

  20. Pediatricians′ perspectives on pneumococcal conjugate vaccines: An exploratory study in the private sector

    Directory of Open Access Journals (Sweden)

    Sanjay Zodpey

    2015-01-01

    Full Text Available There is a lack of information on supply-side determinants, their utilization, and the access to pneumococcal vaccination in India. The objective of this exploratory study was to document the perceptions and perspectives of practicing pediatricians with regard to pneumococcal conjugate vaccines (PCVs in selected metropolitan areas of India. A qualitative study was conducted to generate evidence on the perspective of pediatricians practicing in the private sector regarding pneumococcal vaccination. The pediatricians were identified from 11 metropolitan areas on the basis of PCV vaccine sales in India through multilevel stratified sampling method. Relevant information was collected through in-depth personal interviews. Finally, qualitative data analysis was carried out through standard techniques such as the identification of key domains, words, phrases, and concepts from the respondents. We observed that the majority (67.7% of the pediatricians recommended pneumococcal vaccination to their clients, whereas 32.2% recommended it to only those who could afford it. More than half (62.9% of the pediatricians had no preference for any brand and recommended both a 10-valent pneumococcal conjugate vaccine (PCV10 and a 13-valent PCV (PCV13, whereas 8.0% recommended none. An overwhelming majority (97.3% of the pediatricians reported that the main reason for a patient not following the pediatrician′s advice for pneumococcal vaccination was the price of PCV. To reduce childhood pneumonia-related burden and mortality, pediatricians should use every opportunity to increase awareness about vaccine-preventable diseases, especially vaccine-preventable childhood pneumonia among their patients.

  1. Evidence that pneumococcal serotype replacement in Massachusetts following conjugate vaccination is now complete

    Science.gov (United States)

    Hanage, William P.; Finkelstein, Jonathan A.; Huang, Susan S.; Pelton, Stephen I.; Stevenson, Abbie E.; Kleinman, Ken; Hinrichsen, Virginia L.; Fraser, Christophe

    2010-01-01

    Invasive pneumococcal disease (IPD) has been reduced in the US following conjugate vaccination (PCV7) targeting seven pneumococcal serotypes in 2000. However, increases in IPD due to other serotypes have been observed, in particular 19A. How much this “serotype replacement” will erode the benefits of vaccination and over what timescale is unknown. We used a population genetic approach to test first whether the selective impact of vaccination could be detected in a longitudinal carriage sample, and secondly how long it persisted for following introduction of vaccine in 2000. To detect the selective impact of the vaccine we compared the serotype diversity of samples from pneumococcal carriage in Massachusetts children collected in 2001, 2004 and 2007 with others collected in the pre-vaccine era in Massachusetts, the UK and Finland. The 2004 sample was significantly (p >0.0001) more diverse than pre-vaccine samples, indicating the selective pressure of vaccination. The 2007 sample showed no significant difference in diversity from the pre-vaccine period, and exhibited similar population structure, but with different serotypes. In 2007 the carriage frequency of 19A was similar to that of the most common serotype in pre-vaccine samples. We suggest that serotype replacement involving 19A may be complete in Massachusetts due to similarities in population structure to pre-vaccine samples. These results suggest that the replacement phenomenon occurs rapidly with high vaccine coverage, and may allay concerns about future increases in disease due to 19A. For other serotypes, the future course of replacement disease remains to be determined. PMID:21031138

  2. [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.

  3. Serogroup quantitation of multivalent polysaccharide and polysaccharide-conjugate meningococcal vaccines from China.

    Science.gov (United States)

    Cook, Matthew C; Gibeault, Sabrina; Filippenko, Vasilisa; Ye, Qiang; Wang, Junzhi; Kunkel, Jeremy P

    2013-07-01

    The active components of most meningococcal vaccines are four antigenic serogroup capsular polysaccharides (A, C, Y, W135). The vaccines, monovalent or multivalent mixtures of either free polysaccharides or polysaccharides conjugated to antigenic carrier proteins, may be in liquid or lyophilised formulations, with or without excipients. Acid hydrolysis and chromatographic methods for serogroup quantitation, which were previously optimised and qualified using polysaccharide-based standards and a narrow range of real vaccines, are here challenged with multiple lots of a broad assortment of additional multivalent polysaccharide-based meningococcal vaccine products. Centrifugal filtration successfully removed all interfering lactose excipient without loss of polysaccharides to allow for the determination of Y and W135 serogroups. Replicate operations by three different analysts indicated high method reproducibility. Results indicated some lot-to-lot and product-to-product variations. However, all vaccines were within general specifications for each serogroup polysaccharide, with the exception of all lots of one polysaccharide vaccine - which by these methods were found to be deficient in the serogroup A component only. These robust techniques are very useful for the evaluation of antigen content and consistency of manufacture. The deformulation, hydrolysis and chromatographic methods may be adaptable for the evaluation of other types of polysaccharide-based vaccines.

  4. Persistence of serogroup C antibody responses following quadrivalent meningococcal conjugate vaccination in United States military personnel.

    Science.gov (United States)

    Patel, Manisha; Romero-Steiner, Sandra; Broderick, Michael P; Thomas, Cynthia G; Plikaytis, Brian D; Schmidt, Daniel S; Johnson, Scott E; Milton, Andrea S; Carlone, George M; Clark, Thomas A; Messonnier, Nancy E; Cohn, Amanda C; Faix, Dennis J

    2014-06-24

    Serogroup C meningococcal (MenC) disease accounts for one-third of all meningococcal cases and causes meningococcal outbreaks in the U.S. Quadrivalent meningococcal vaccine conjugated to diphtheria toxoid (MenACYWD) was recommended in 2005 for adolescents and high risk groups such as military recruits. We evaluated anti-MenC antibody persistence in U.S. military personnel vaccinated with either MenACYWD or meningococcal polysaccharide vaccine (MPSV4). Twelve hundred subjects vaccinated with MenACYWD from 2006 to 2008 or MPSV4 from 2002 to 2004 were randomly selected from the Defense Medical Surveillance System. Baseline serologic responses to MenC were assessed in all subjects; 100 subjects per vaccine group were tested during one of the following six post-vaccination time-points: 5-7, 11-13, 17-19, 23-25, 29-31, or 35-37 months. Anti-MenC geometric mean titers (GMT) were measured by rabbit complement serum bactericidal assay (rSBA) and geometric mean concentrations (GMC) by enzyme-linked immunosorbent assay (ELISA). Continuous variables were compared using the Wilcoxon rank sum test and the proportion of subjects with an rSBA titer ≥ 8 by chi-square. Pre-vaccination rSBA GMT was antibody.

  5. Meningococcal quadrivalent (serogroups A, C, W135 and Y) tetanus toxoid conjugate vaccine (Nimenrix™).

    Science.gov (United States)

    Croxtall, Jamie D; Dhillon, Sohita

    2012-12-24

    Nimenrix™ (MenACWY-TT) is a quadrivalent meningococcal conjugate vaccine, comprising the polysaccharide serogroups A, C, W135 and Y, and tetanus toxoid (TT) as carrier protein. It is the first quadrivalent vaccine (administered as a single dose) to be approved in Europe for active immunization of individuals aged ≥ 12 months against invasive meningococcal disease caused by Neisseria meningitidis serogroups A, C, W135 and Y. Administration of a single dose of Nimenrix™ elicited a strong immune response against all four vaccine serogroups in healthy toddlers aged 12-23 months, children and adolescents aged 2-17 years and adults aged 18-55 years in randomized, multicentre, phase III trials. In toddlers, Nimenrix™ was noninferior to Meningitec® in terms of seroresponse rates against meningococcal serogroup C 42 days post-vaccination. In children, adolescents and adults, Nimenrix™ was noninferior to Mencevax™ in terms of vaccination response rates against all four serogroups 1 month post-vaccination. Furthermore, several phase II studies and a phase III trial showed that the immune response elicited by Nimenrix™ in all age groups persisted for 7-42 months after the primary vaccination (when evaluated by rabbit serum bactericidal activity), with the vaccine also inducing immune memory in toddlers. In addition, several randomized, multicentre, phase III, noninferiority trials showed that when coadministered with other childhood vaccines or a seasonal flu vaccine, the immunogenicity of Nimenrix™ or that of the coadministered vaccine was generally not altered. Nimenrix® was generally well tolerated in all age groups whether administered as a single vaccine or coadministered with other routine vaccines. The incidence of grade 3 local or systemic solicited adverse events during the first 4 days following vaccination and of serious adverse events over an extended follow-up period of up to 6 months was low (<4.5%). Although protective effectiveness and longer

  6. 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

  7. 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

  8. A bicomponent Plasmodium falciparum investigational vaccine composed of protein-peptide conjugates.

    Science.gov (United States)

    Kubler-Kielb, Joanna; Majadly, Fathy; Biesova, Zuzana; Mocca, Christopher P; Guo, Chunyan; Nussenzweig, Ruth; Nussenzweig, Victor; Mishra, Satish; Wu, Yimin; Miller, Louis H; Keith, Jerry M; Liu, Teh-Yung; Robbins, John B; Schneerson, Rachel

    2010-01-19

    There is yet no licensed vaccine against malaria, a serious human disease affecting mostly children, with an annual death rate of about one million. Plasmodia, the malaria-causing parasites, have two obligatory hosts: mammals or birds, in which they multiply asexually, and mosquitoes with sexual multiplication. The most common and serious type of malaria is caused by Plasmodium falciparum. The circumsporozoite protein (CSP), a major surface antigen of sporozoites, is a protective antigen. A unique feature of P. falciparum CSP is its large central domain composed of over 30 tetrapeptide repeats of Asn-Ala-Asn-Pro (NANP). Several NANP peptide-protein conjugates were tested clinically but elicited a low level of CSP antibodies for a short duration. To provide a CSP-based candidate vaccine, we investigated recombinant CSP and NANP conjugates of various peptide lengths, with different N-terminal amino acids, bound at different ratios to various carrier proteins. Injected into mice, CSP alone and CSP or NANP conjugates induced antibodies with booster responses and were positive by the sporozoite immunofluorescent assay. The use of the mosquito stage P. falciparum ookinete surface protein, Pfs25, cross-linked onto itself as a carrier for NANP, induced in mice high levels of uniquely long-lasting antibodies to both vaccine components with secondary biological activities, that will provide immunity to liver infection by sporozoites and block transmission by mosquitoes.

  9. The adjuvant effect of TLR7 agonist conjugated to a meningococcal serogroup C glycoconjugate vaccine.

    Science.gov (United States)

    Donadei, Agnese; Balocchi, Cristiana; Mancini, Francesca; Proietti, Daniela; Gallorini, Simona; O'Hagan, Derek T; D'Oro, Ugo; Berti, Francesco; Baudner, Barbara C; Adamo, Roberto

    2016-10-01

    Conjugation of a small molecule immunopotentiator to antigens has been proposed to deliver the ligand to the receptor, localize its action and minimize systemic inflammation. However, the effect of conjugation of Toll like receptor 7 agonists (TLR7a) on the immunogenicity of carbohydrate-based vaccines is unknown. In this study we synthesized an anti-Neisseria meningitidis serogroup C (MenC) glycoconjugate vaccine composed of MenC oligosaccharide antigens covalently linked to the carrier protein CRM197, to which a TLR7a was in turn conjugated. This vaccine was able to activate in vitro the TLR7 comparably to the unconjugated ligand. The magnitude and the quality of the immune response against MenC capsular polysaccharide were evaluated in mice, comparing the MenC-CRM-TLR7a construct to a MenC-CRM197 vaccine, prepared through the same conjugation chemistry and co-administered with the unconjugated TLR7a. A commercially licensed anti-MenC glycoconjugate was used as further control to determine the influence of the coupling approach and the level of carbohydrate incorporation on the anti-MenC immune response. The possible additive effect of co-administration with Alum hydroxide (AlumOH) was also examined. The bactericidal titers against N. meningitidis were in agreement with the elicited anti-carbohydrate IgGs, and unequivocally showed that TLR7a conjugation to CRM197 enhanced the anti-MenC immune response. TLR7a conjugation induced a shift to a Th1 type response, as assessed by the increased IgG2a subclass production, both in the absence and in the presence of AlumOH. The increased immune response was clearly present only in the absence of AlumOH and was less pronounced than the co-administration of a licensed glycoconjugate with a standard dose of TLR7a-phosphonate adsorbed on the inorganic salt. The amount of MenC saccharide that was covalently linked to CRM197 after previous CRM197-TLR7a conjugation resulted in lower responses than achieved with conventional Men

  10. Effect of Vaccination with Carrier Protein on Response to Meningococcal C Conjugate Vaccines and Value of Different Immunoassays as Predictors of Protection

    OpenAIRE

    Burrage, Moya; Robinson, Andrew; Borrow, Ray; Andrews, Nick; Southern, Joanna; Findlow, Jamie; Martin, Sarah; Thornton, Carol; Goldblatt, David; Corbel, Michael; Sesardic, Dorothea; Cartwight, Keith; Richmond, Peter; Miller, Elizabeth

    2002-01-01

    In order to plan for the wide-scale introduction of meningococcal C conjugate (MCC) vaccine for United Kingdom children up to 18 years old, phase II trials were undertaken to investigate whether there was any interaction between MCC vaccines conjugated to tetanus toxoid (TT) or a derivative of diphtheria toxin (CRM197) and diphtheria-tetanus vaccines given for boosting at school entry or leaving. Children (n = 1,766) received a diphtheria-tetanus booster either 1 month before, 1 month after, ...

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

    Science.gov (United States)

    Tartof, Sara Y; 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

    2017-07-14

    Quadrivalent meningococcal conjugate vaccine is recommended for children, adolescents, and adults at increased risk of meningococcal disease. In 2011, MenACWY-CRM (Menveo, GSK) was approved for children aged 2-10 years in the U.S. 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 pre-specified events of interest (EOIs) and serious medically attended events (SMAEs) from inpatient or emergency settings up to one year following MenACWY-CRM vaccination. SMAEs were categorized by ICD-9 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 one myasthenia gravis case underwent chart review which confirmed one incident asthma case occurring 237 days after concomitant vaccination with MenACWY-CRM and typhoid vaccine. Thirty-one children experienced SMAEs, most commonly due to 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.

  12. 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

  13. 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......) and 8 pigs were vaccinated with Ap5bCP-TT and adjuvant (group 0). Pigs vaccinated with Ap5bCP-TT developed antibody responses to the capsular polysaccharide from A. pleuropneumoniae serotype 5b (Ap5bCP). After challenge, all pigs in groups A and B had severe clinical signs of disease and were euthanized...... and pulmonary lesions caused by experimental infection with A. pleuropneumoniae serotype 5b....

  14. 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.

  15. 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...... children and adults. Despite its potential importance, the possible influence of preexisting immunity to the components of such conjugates on the vaccination response in humans has been addressed by few studies. To study this issue, we randomized 82 healthy adult volunteers into six groups and vaccinated...... and the anti-HibCP immunoglobulin G1 (IgG1) and IgG2 levels were measured before and 4 weeks after the immunizations. For some of the vaccinees, the number of circulating antibody-secreting cells was evaluated 7 days after immunization. Surprisingly, preimmunization with the relevant carrier protein reduced...

  16. 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.

  17. Experimental design to optimize an Haemophilus influenzae type b conjugate vaccine made with hydrazide-derivatized tetanus toxoid.

    Science.gov (United States)

    Laferriere, Craig; Ravenscroft, Neil; Wilson, Seanette; Combrink, Jill; Gordon, Lizelle; Petre, Jean

    2011-10-01

    The introduction of type b Haemophilus influenzae conjugate vaccines into routine vaccination schedules has significantly reduced the burden of this disease; however, widespread use in developing countries is constrained by vaccine costs, and there is a need for a simple and high-yielding manufacturing process. The vaccine is composed of purified capsular polysaccharide conjugated to an immunogenic carrier protein. To improve the yield and rate of the reductive amination conjugation reaction used to make this vaccine, some of the carboxyl groups of the carrier protein, tetanus toxoid, were modified to hydrazides, which are more reactive than the ε -amine of lysine. Other reaction parameters, including the ratio of the reactants, the size of the polysaccharide, the temperature and the salt concentration, were also investigated. Experimental design was used to minimize the number of experiments required to optimize all these parameters to obtain conjugate in high yield with target characteristics. It was found that increasing the reactant ratio and decreasing the size of the polysaccharide increased the polysaccharide:protein mass ratio in the product. Temperature and salt concentration did not improve this ratio. These results are consistent with a diffusion controlled rate limiting step in the conjugation reaction. Excessive modification of tetanus toxoid with hydrazide was correlated with reduced yield and lower free polysaccharide. This was attributed to a greater tendency for precipitation, possibly due to changes in the isoelectric point. Experimental design and multiple regression helped identify key parameters to control and thereby optimize this conjugation reaction.

  18. 75 FR 48707 - Proposed Vaccine Information Materials for Pneumococcal Conjugate Vaccine and Human...

    Science.gov (United States)

    2010-08-11

    ... substitute for cervical cancer screening. Women should still get regular Pap tests. The vaccine you are... Vaccine: What You Need to Know 1. Pneumococcal Disease Infection with Streptococcus pneumoniae bacteria can make children very sick. It causes blood infections, pneumonia, and meningitis, mostly in young...

  19. 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

    2005-10-01

    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.

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

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    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.

  1. Comparative evaluation of a newly developed 13-valent pneumococcal conjugate vaccine in a mouse model.

    Science.gov (United States)

    Park, Chulmin; Kwon, Eun-Young; Choi, Su-Mi; Cho, Sung-Yeon; Byun, Ji-Hyun; Park, Jung Yeon; Lee, Dong-Gun; Kang, Jin Han; Shin, Jinhwan; Kim, Hun

    2016-12-14

    Animal models facilitate evaluation of vaccine efficacy at relatively low cost. This study was a comparative evaluation of the immunogenicity and protective efficacy of a new 13-valent pneumococcal conjugate vaccine (PCV13) with a control vaccine in a mouse model. After vaccination, anti-capsular antibody levels were evaluated by pneumococcal polysaccharide (PnP) enzyme-linked immunosorbent assay (ELISA) and opsonophagocytic killing assay (OPA). Also, mice were challenged intraperitoneally with 100-fold of the 50% lethal dose of Streptococcus pneumoniae. The anti-capsular IgG levels against serotypes 1, 4, 7F, 14, 18C, 19A, and 19F were high (quartile 2 >1,600), while those against the other serotypes were low (Q2 ≤ 800). Also, the OPA titres were similar to those determined by PnP ELISA. Comparative analysis between new PCV13 and control vaccination group in a mouse model exhibited significant differences in serological immunity of a few serotypes and the range of anti-capsular IgG in the population. Challenge of wild-type or neutropenic mice with serotypes 3, 5, 6A, 6B, and 9V showed protective immunity despite of induced relatively low levels of anti-capsular antibodies. With comparison analysis, a mouse model should be adequate for evaluating serological efficacy and difference in the population level as preclinical trial.

  2. 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

  3. Brazilian meningococcal C conjugate vaccine: physicochemical, immunological, and thermal stability characteristics.

    Science.gov (United States)

    Bastos, Renata Chagas; Corrêa, Marilza Batista; de Souza, Iaralice Medeiros; da Silva, Milton Neto; da Silva Gomes Pereira, Denise; Martins, Fernanda Otaviano; da Silva Faria, Camila; Ano Bom, Ana Paula Dinis; de Lourdes Leal, Maria; Jessouroun, Ellen; da Silva, José Godinho; de Andrade Medronho, Ricardo; da Silveira, Ivna Alana Freitas Brasileiro

    2017-09-19

    High temperature is known to cause some instability in polysaccharide-protein conjugated vaccines and studies under stress conditions may be useful in determining whether short-term accidental exposure to undesired conditions can compromise product quality. In this study, we examined the structural stability of three industrial batches of Brazilian Meningococcal C conjugate bulk (MPCT) incubated at 4, 37, and 55 °C for 5 weeks. The effect of exposure to the storage temperatures was monitored by HPLC-SEC, CZE, CD and NMR techniques. The immunological significance of any physicochemical changes observed in MPCT was determined by SBA and ELISA assays of serum from immunized mice. Fluorescence emission spectra at 4 and 37 °C were similar among all samples and compatible with the native fold of the carrier protein. Fluorescence spectra of MPCT stored at 55 °C decreased in intensity and had a significant red-shift, indicating conformational changes. Far-UV CD spectra revealed a trend toward loss of structural conformation as storage temperature was increased to 55 °C. The NMR data showed modified signal intensity of the aromatic and aliphatic residues, mainly for samples incubated at 55 °C, suggesting a partial loss of tertiary structure. About 50% free saccharide content was found in bulks stored at 55 °C, but no difference was observed in the IgG or SBA titers. The present study showed physicochemical methods alone are insufficient to predict the biological activity of a MPCT conjugate vaccine without extensive validation against immunological data. However, they provide a sensitive means of detecting changes induced in a vaccine exposed to adverse environmental condition.

  4. 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.

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

    Science.gov (United States)

    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.

  6. 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.

  7. Impact of Pneumococcal Conjugate Vaccine on Pediatric Tympanostomy Tube Insertion in Partial Immunized Population

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    Mao-Che Wang

    2015-01-01

    Full Text Available Objective. To investigate the impact of seven-valent pneumococcal conjugate vaccine on tube insertions in a partial immunized pediatric population. Study Design. Retrospective ecological study. Methods. This study used Taiwan National Health Insurance Research Database for the period 2000–2009. Every child under 17 years old who received tubes during this 10-year period was identified and analyzed. The tube insertion rates in different age groups and the risk to receive tubes in different birth cohorts before and after the release of the vaccine in 2005 were compared. Results. The tube insertion rates for children under 17 years of age ranged from 21.6 to 31.9 for 100,000 persons/year. The tube insertion rate of children under 2 years old decreased significantly after 2005 in period effect analysis (β = −0.074, P < 0.05, and the negative β value means a downward trend and increased in children 2 to 9 years old throughout the study period (positive β values which mean upward trends, P < 0.05. The rate of tube insertion was lower in 2004-2005 and 2006-2007 birth cohorts than that of 2002-2003 birth cohort (RR = 0.90 and 0.21, 95% CI 0.83–0.97 and 0.19–0.23, resp.. Conclusion. The seven-valent pneumococcal conjugate vaccine may reduce the risk of tube insertion for children of later birth cohorts. The vaccine may have the protective effect on tube insertions in a partial immunized pediatric population.

  8. Long-term thermal stability of group C meningococcal polysaccharide-tetanus toxoid conjugate vaccine.

    Science.gov (United States)

    Lee, Shwu-Maan; Petermann, Robert; Porte, Quallyna; Berezuk, Greg; Crowe, Brian; Shirtz, John

    2007-01-01

    The stability of vaccines during storage and handling is a prerequisite for optimal potency at the time of immunization. Meningococcal group C conjugate vaccines have been successfully incorporated in mass immunization programs, however, thus far no long-term real-time stability studies of these vaccines have been reported. Stability of de-O-acetylated group C meningococcal polysaccharide coupled to tetanus toxoid (GCMP-TT) was evaluated in real time on the basis of immunogenicity and physiochemical properties. The vaccine is formulated as a 0.5 mL suspension containing 10 mug GCMP conjugated to 10-20 mug of TT adsorbed on 0.5 mg aluminum in saline. The single dose syringes were stored under refrigeration (5 +/- 3 degrees C) and at room temperature (25 +/- 2 degrees C) for up to 42 months and at elevated temperature (40 +/- 2 degrees C) for up to 6 months. At both refrigerated and room temperatures, no time-dependent change in animal potency was detectable through 42 months. After the nine months maximum recommended storage period at room temperature, 96% of the baseline serum bactericidal antibody (SBA) titer was maintained. Time-dependent decreases in SBA level and anti-GCMP-TT IgG level were observed at 40 +/- 2 degrees C. No changes in GCMP-TT adsorption and pH occurred in all the studies. Loss of integrity increased over six months at 40 +/- 2 degrees C (p = 0.004). Free sugar content did not change over 36 months under refrigeration. GCMP-TT retained immunogenicity and physicochemical properties under refrigeration and at room temperature (25 +/- 2 degrees C) for up to 42 months.

  9. Comparison of immunogenicity and safety of an influenza vaccine administered concomitantly with a 13-valent pneumococcal conjugate vaccine or 23-valent polysaccharide pneumococcal vaccine in the elderly

    Science.gov (United States)

    2017-01-01

    Purpose Previous studies have demonstrated the immunogenicity and safety of the co-administration of the trivalent inactivated influenza vaccine (IIV3) with the polysaccharide pneumococcal vaccine (PPV) or pneumococcal conjugate vaccine (PCV). However, there is no direct comparison study that evaluates the immunogenicity and safety of IIV3 given concomitantly with PCV13 or PPV23 in the elderly. Materials and Methods During the 2012-2013 influenza vaccination period, 224 healthy elderly volunteers aged 65 years and older randomly received IIV3 given concomitantly with either PCV13 (PCV13+IIV3) or PPV23 (PPV23+IIV3) in a 1:1 ratio. Serum hemagglutination-inhibiting antibodies for IIV3 were measured at the time of vaccination and 1 month after vaccination. Adverse events were recorded prospectively in a clinical diary during a 7-day period. Results A total of 220 participants blood samples for analysis of immunogenicity and kept a clinical diary for safety analysis (PCV13+IIV3, n=110; PPV23+IIV3, n=110). One month after vaccination, both groups satisfied the Committee for Medical Products for Human Use criteria for A/H1N1, A/H3N2 and B strains, showing comparable seroprotection rates, seroconversion rates and geometric mean titer fold. The assessments of immunogenicity were similar in both groups. The most common local and systemic reactions were pain at the injection site and generalized myalgia. They were generally mild or moderate in intensity. The adverse events were not statistically different between the two groups. Conclusion PCV13+IIV3 and PPV23+IIV3 demonstrated similar immunogenicity and safety in the elderly.

  10. Long-term impact of pneumococcal polysaccharide vaccination on nasopharyngeal carriage in children previously vaccinated with various pneumococcal conjugate vaccine regimes.

    Science.gov (United States)

    Boelsen, Laura K; Dunne, Eileen M; Lamb, Karen E; Bright, Kathryn; Cheung, Yin Bun; Tikoduadua, Lisi; Russell, Fiona M; Mulholland, E Kim; Licciardi, Paul V; Satzke, Catherine

    2015-10-13

    Previously, the Fiji Pneumococcal Project (FiPP) evaluated reduced dose immunization schedules that incorporated pneumococcal protein conjugate and/or polysaccharide vaccine (PCV7 and 23vPPV, respectively). Immune hyporesponsiveness was observed in children vaccinated with 23vPPV at 12 months of age compared with children who did not receive 23vPPV. Here we assess the long-term impact of 23vPPV vaccination on nasopharyngeal carriage rates and densities of Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus and Moraxella catarrhalis. Nasopharyngeal swabs (n=194) were obtained from healthy children who participated in FiPP (now aged 5-7 years). S. pneumoniae were isolated and identified by standard culture-based methods, and serotyped using latex agglutination and the Quellung reaction. Carriage rates and densities of S. pneumoniae, H. influenzae, S. aureus and M. catarrhalis were determined using real-time quantitative PCR. There were no differences in the rate or density of S. pneumoniae, H. influenzae or M. catarrhalis carriage by PCV7 dose or 23vPPV vaccination in the vaccinated participants overall. However, differences were observed between the two main ethnic groups: Fijian children of Indian descent (Indo-Fijian) were less likely to carry S. pneumoniae, H. influenzae and M. catarrhalis, and there was evidence of a higher carriage rate of S. aureus compared with indigenous Fijian (iTaukei) children. Polysaccharide vaccination appeared to have effects that varied between ethnic groups, with 23vPPV vaccination associated with a higher carriage rate of S. aureus in iTaukei children, while there was a lower carriage rate of S. pneumoniae associated with 23vPPV vaccination in Indo-Fijian children. Overall, polysaccharide vaccination had no long-term impact on pneumococcal carriage, but may have impacted on S. aureus carriage and have varying effects in ethnic groups, suggesting current WHO vaccine schedule recommendations against the use of 23v

  11. TLR9-adjuvanted pneumococcal conjugate vaccine induces antibody-independent memory responses in HIV-infected adults.

    Science.gov (United States)

    Offersen, Rasmus; Melchjorsen, Jesper; Paludan, Søren R; Østergaard, Lars; Tolstrup, Martin; Søgaard, Ole S

    2012-08-01

    HIV-patients have excess of pneumococcal infection. We immunized 40 HIV-patients twice with pneumococcal conjugate vaccine (Prevnar, Pfizer) +/- a TLR9 agonist (CPG 7909). Peripheral blood mononuclear cells were stimulated with pneumococcal polysaccharides and cytokine concentrations measured. The CPG 7909 adjuvant group had significantly higher relative cytokine responses than the placebo group for IL-1β, IL-2R, IL-6, IFN-γ and MIP-β, which, did not correlate with IgG antibody responses. These findings suggests that CPG 7909 as adjuvant to pneumococcal conjugate vaccine induces cellular memory to pneumococcal polysaccharides in HIV-patients, independently of the humoral response.

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

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    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.

  13. Pneumococcal conjugate vaccine (Prevnar; PNCRM7): a review of its use in the prevention of Streptococcus pneumoniae infection.

    Science.gov (United States)

    Darkes, Malcolm J M; Plosker, Greg L

    2002-01-01

    PNCRM7 (Prevnar) is a pneumococcal vaccine containing seven capsular polysaccharide antigens from the bacterium Streptococcus pneumoniae, each of which is conjugated to diphtheria protein [cross-reactive material (CRM(197))]. CRM(197) is an inert but immunogenic variant of diphtheria toxoid that is also used as a carrier molecule in one Haemophilus influenzae type b conjugate vaccine. Unlike the 23-valent unconjugated pneumococcal vaccines, PNCRM7 elicits a T cell-dependent response and thus protects young children against pneumococcal disease. The immunogenicity of PNCRM7 has been demonstrated in both healthy children aged or =38 degrees C) that usually resolved without treatment. The limited available pharmacoeconomic data suggest that PNCRM7 could be cost effective depending, in part, on the manufacturer's list price of the vaccine. Results of the base case analysis in a US study showed a cost-effectiveness ratio for PNCRM7 of US dollars 80,000 per life-year saved from a societal perspective compared with US dollars 176,000 from a healthcare payer perspective, assuming a nondiscounted list price of US dollars 58 per dose (1997 costs). Concomitant administration of PNCRM7 vaccine with hepatitis B, oral polio, meningococcal oligosaccharide protein conjugate or H. influenzae type b vaccines did not affect the immunogenicity of these pediatric vaccines to a clinically relevant extent. PNCRM7 vaccine will be of great benefit to those societies that have active immunization programs implemented. In infants and vulnerable children throughout the world, PNCRM7 vaccine has the potential to reduce the mortality and morbidity rates associated with S. pneumoniae infections. In developed countries, the vaccine will be of particular benefit in preventing disabling infections but its impact in developing countries will be more pronounced with the potential to greatly reduce mortality.

  14. 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

    BACKGROUND: Patients with Crohn's disease (CD) have a higher risk of infectious diseases including pneumococcal infections, and the risk increases with immunotherapy. The primary endpoint of this study was to investigate the specific antibody response to two pneumococcal vaccines in CD patients...... with and without immunosuppressive treatment four weeks post vaccination. METHODS: In a randomized trial of the 23-valent pneumococcal polysaccharide vaccine (PPV23) and the 13-valent pneumococcal conjugated vaccine (PCV13), a group of CD patients treated with immunosuppressive drugs (IS) alone or in combination...... with TNF-α antagonists were compared to a group of CD patients not treated with any of these drugs (untreated). Specific pneumococcal antibody concentrations were measured against 12 serotypes common to the two vaccines before and 4 week after vaccination. RESULTS: PCV13 induced a significantly higher...

  15. 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.

  16. [Advice of the French Superior Council on Public Health (section on transmissible diseases) relative to vaccination by heptavalent pneumococcal conjugate vaccine (Prevanar). Meeting of March 8, 2002].

    Science.gov (United States)

    2002-08-01

    This article is the full-length text (including arguments and recommendations) written by the Conseil Supérieur d'Hygiène Publique de France, in its session of march 8th 2002, expressing its opinion on the immunization policy with the heptavalent pneumococcal conjugate vaccine (Prevenar).

  17. 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

  18. Efficacy and safety of seven-valent conjugate pneumococcal vaccine in American Indian children: group randomised trial.

    Science.gov (United States)

    O'Brien, Katherine L; Moulton, Lawrence H; Reid, Raymond; Weatherholtz, Robert; Oski, Jane; Brown, Laura; Kumar, Gaurav; Parkinson, Alan; Hu, Diana; Hackell, Jill; Chang, Ih; Kohberger, Robert; Siber, George; Santosham, Mathuram

    2003-08-02

    Streptococcus pneumoniae is the main cause of invasive bacterial disease in children aged younger than 2 years. Navajo and White Mountain Apache children have some of the highest rates of invasive pneumococcal disease documented in the world. We aimed to assess the safety and efficacy of a seven-valent polysaccharide protein conjugate pneumococcal vaccine (PnCRM7) against such disease. In a group-randomised study, we gave this vaccine to children younger than 2 years from the Navajo and White Mountain Apache Indian reservations; meningococcal type C conjugate vaccine (MnCC) served as the control vaccine. Vaccine schedules were determined by age at enrollment. We recorded episodes of invasive pneumococcal disease and serotyped isolates. Analyses were by intention to treat and per protocol. 8292 children enrolled in the trial. In the per protocol analysis of the primary efficacy group (children enrolled by 7 months of age) there were eight cases of vaccine serotype disease in the controls and two in the PnCRM7 group; in the intention-to-treat analysis we noted 11 cases of vaccine serotype disease in the MnCC control group and two in the PnCRM7 group. After group randomisation had been controlled for, the per protocol primary efficacy of PnCRM7 was 76.8% (95% CI -9.4% to 95.1%) and the intention-to-treat total primary efficacy was 82.6% (21.4% to 96.1%). PnCRM7 vaccine prevents vaccine serotype invasive pneumococcal disease even in a high risk population. Other regions with similar disease burden should consider including this vaccine in the routine childhood vaccine schedule.

  19. 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...

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

    Directory of Open Access Journals (Sweden)

    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. 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.

  2. Immunogenicity of three Haemophilus influenzae type b protein conjugate vaccines in HIV seropositive adults and analysis of predictors of vaccine response.

    Science.gov (United States)

    Dockrell, D H; Poland, G A; Steckelberg, J M; Wollan, P C; Strickland, S R; Pomeroy, C

    1999-07-16

    HIV-seropositive adults may be at increased risk of infection due to Haemophilus influenzae type b (Hib) as compared with HIV-seronegative adults. Protein conjugate vaccines have been demonstrated to induce protective levels of antibodies against Hib in immunocompetent infants and also in HIV-seropositive infants. In this study we determined the immunogenicity of three protein conjugate Hib vaccines (PRP-D, HbOC, HbNOMP) in 135 HIV-seropositive adults who received one dose of Hib vaccine. Anti-polyribosylribitol phosphate (PRP) antibodies were measured at 0, 1, 3 and 12 months postimmunization by the Farr method. We demonstrate that all three vaccines are highly immunogenic and result in protective (> 1.0 microg/ml) levels of antibody. Overall the anti-PRP antibody level was > 1.0 microg/ml in 26% of patients preimmunization, 91% at both 1 and 3 months, and 79% at 12 months postvaccination. Comparison of responses to the three vaccines over time demonstrated differences in the mean geometric anti-PRP antibody level at 1 month (p=0.03) and the 12 month time points (p=0.03) with lower geometric mean levels in the HbNOMP group, though baseline differences in groups limit the interpretation of these findings. In a univariate analysis of baseline characteristics which predicted poor vaccine response, low total IgG2 levels preimmunization predicted a poor antibody response at 1 month (p < 0.01) and at 12 months (p=0.05), while low CD4 T-cell count predicted poor response at 12 months (p < 0.01). We conclude that all three US licensed protein conjugate Hib vaccines are immunogenic in HIV-seropositive adults, and that baseline CD4 T-cell count and IgG2 levels predict the likelihood of antibody response to vaccine.

  3. 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

    2008-01-01

    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 simulta

  4. 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

  5. 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.

  6. Direct Comparison of Immunogenicity Induced by 10- or 13-Valent Pneumococcal Conjugate Vaccine around the 11-Month Booster in Dutch Infants

    NARCIS (Netherlands)

    Wijmenga-Monsuur, Alienke J; van Westen, Els; Knol, Mirjam J; Jongerius, Riet M C; Zancolli, Marta; Goldblatt, David; van Gageldonk, Pieter G M; Tcherniaeva, Irina; Berbers, Guy A M; Rots, Nynke Y

    2015-01-01

    BACKGROUND & AIMS: 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

  7. Clinical Safety and Immunogenicity of Tumor-Targeted, Plant-Made Id-KLH Conjugate Vaccines for Follicular Lymphoma

    Directory of Open Access Journals (Sweden)

    Daniel Tusé

    2015-01-01

    Full Text Available We report the first evaluation of plant-made conjugate vaccines for targeted treatment of B-cell follicular lymphoma (FL in a Phase I safety and immunogenicity clinical study. Each recombinant personalized immunogen consisted of a tumor-derived, plant-produced idiotypic antibody (Ab hybrid comprising the hypervariable regions of the tumor-associated light and heavy Ab chains, genetically grafted onto a common human IgG1 scaffold. Each immunogen was produced in Nicotiana benthamiana plants using twin magnICON vectors expressing the light and heavy chains of the idiotypic Ab. Each purified Ab was chemically linked to the carrier protein keyhole limpet hemocyanin (KLH to form a conjugate vaccine. The vaccines were administered to FL patients over a series of ≥6 subcutaneous injections in conjunction with the adjuvant Leukine (GM-CSF. The 27 patients enrolled in the study had previously received non-anti-CD20 cytoreductive therapy followed by ≥4 months of immune recovery prior to first vaccination. Of 11 patients who became evaluable at study conclusion, 82% (9/11 displayed a vaccine-induced, idiotype-specific cellular and/or humoral immune response. No patients showed serious adverse events (SAE related to vaccination. The fully scalable plant-based manufacturing process yields safe and immunogenic personalized FL vaccines that can be produced within weeks of obtaining patient biopsies.

  8. Antibody responses of three Haemophilus influenzae type b conjugate vaccines after one, two and three doses in Filipino children.

    Science.gov (United States)

    Capeding, M R; Nohynek, H; Käyhty, H; Pascual, L G; Sunico, E S; Tamundong, A A; Ruutu, P

    1998-01-01

    Differences in the magnitude of antibody response after one, two or three doses of Haemophilus influenzae type b conjugate vaccines have been reported which may influence decision-making regarding which vaccine should be used. This is of particular importance in developing countries where children may not receive a full immunization series and the vaccination schedule may be delayed. Serum antibody responses to three Hib capsular polysaccharide protein conjugate vaccines (PRP-OMP, HbOC and PRP-T) were evaluated in 102 Filipino infants. Vaccination was carried out at 6, 10 and 14 weeks of age based on the national Expanded Programme on Immunization (EPI) schedule together with diphtheria-tetanus-pertussis, hepatitis B and oral poliomyelitis vaccines. Sera were collected at 6 weeks and 1 month after each vaccination. Anti-Hib polysaccharide antibody concentrations were determined by Farrtype radioimmunoassay (RIA) and enzymeimmunoassay (EIA), Following the first dose, the geometric mean concentrations (GMC, micrograms ml-1) for PRP-OMP, HbOC and PRP-T were 0.69, 0.27 and 0.38, respectively. After two doses, there was a significant response (P antibody responses were noted. The anti-Hib antibody concentrations determined by RIA and EIA were also compared in order to validate the latter for use in laboratories where it is feasible. There was a good correlation (r2 = 76%; P = 0.0001) in the Hib antibody titres obtained by both assays.

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

    Science.gov (United States)

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

    2014-01-01

    Background: 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). Results: 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. Conclusion: 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. Methods: 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. PMID:24220326

  10. 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

  11. [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.

  12. Impact of pneumococcal conjugate vaccine in children morbidity and mortality in Peru: Time series analyses.

    Science.gov (United States)

    Suarez, Victor; Michel, Fabiana; Toscano, Cristiana M; Bierrenbach, Ana Luiza; Gonzales, Marco; Alencar, Airlane Pereira; Ruiz Matus, Cuauhtemoc; Andrus, Jon K; de Oliveira, Lucia H

    2016-09-01

    Streptococcus pneumoniae is the leading cause of bacterial pneumonia, meningitis and sepsis in children worldwide. Despite available evidence on pneumococcal conjugate vaccine (PCV) impact on pneumonia hospitalizations in children, studies demonstrating PCV impact in morbidity and mortality in middle-income countries are still scarce. Given the disease burden, PCV7 was introduced in Peru in 2009, and then switched to PCV10 in late 2011. National public healthcare system provides care for 60% of the population, and national hospitalization, outpatient and mortality data are available. We thus aimed to assess the effects of routine PCV vaccination on pneumonia hospitalization and mortality, and acute otitis media (AOM) and all cause pneumonia outpatient visits in children under one year of age in Peru. We conducted a segmented time-series analysis using outcome-specific regression models. Study period was from January 2006 to December 2012. Data sources included the National information systems for hospitalization, mortality, outpatient visits, and RENACE, the national database of aggregated weekly notifications of pneumonia and other acute respiratory diseases (both hospitalized and non-hospitalized). Study outcomes included community acquired pneumonia outpatient visits, hospitalizations and deaths (ICD10 codes J12-J18); and AOM outpatient visits (H65-H67). Monthly age- and sex-specific admission, outpatient visit, and mortality rates per 100,000 children aged impact in morbidity and mortality in children aged <1year. Vaccine effectiveness was 26.2% (95% CI 16.9-34.4) for AOM visits, 35% (95% CI 8.6-53.8) for mortality due to pneumonia, and 20.6% (95% CI 10.6-29.5) for weekly cases of pneumonia hospitalization and outpatient visits notified to RENACE. We used secondary data sources which are usually developed for other non-epidemiologic purposes. Despite some data limitations, our results clearly demonstrate the overall benefit of PCV vaccination in Peru.

  13. Continued Impact of Pneumococcal Conjugate Vaccine on Carriage in Young Children

    Science.gov (United States)

    Huang, Susan S.; Hinrichsen, Virginia L.; Stevenson, Abbie E.; Rifas-Shiman, Sheryl L.; Kleinman, Ken; Pelton, Stephen I.; Lipsitch, Marc; Hanage, William P.; Lee, Grace M.; Finkelstein, Jonathan A.

    2009-01-01

    OBJECTIVES The goals were to assess serial changes in Streptococcus pneumoniae serotypes and antibiotic resistance in young children and to evaluate whether risk factors for carriage have been altered by heptavalent pneumococcal conjugate vaccine (PCV7). METHODS Nasopharyngeal specimens and questionnaire/medical record data were obtained from children 3 months to <7 years of age in primary care practices in 16 Massachusetts communities during the winter seasons of 2000–2001 and 2003–2004 and in 8 communities in 2006–2007. Antimicrobial susceptibility testing and serotyping were performed with S pneumoniae isolates. RESULTS We collected 678, 988, and 972 specimens during the sampling periods in 2000–2001, 2003–2004, and 2006–2007, respectively. Carriage of non-PCV7 serotypes increased from 15% to 19% and 29% (P < .001), with vaccine serotypes decreasing to 3% of carried serotypes in 2006–2007. The relative contribution of several non-PCV7 serotypes, including 19A, 35B, and 23A, increased across sampling periods. By 2007, commonly carried serotypes included 19A (16%), 6A (12%), 15B/C (11%), 35B (9%), and 11A (8%), and high-prevalence serotypes seemed to have greater proportions of penicillin nonsusceptibility. In multivariate models, common predictors of pneumococcal carriage, such as child care attendance, upper respiratory tract infection, and the presence of young siblings, persisted. CONCLUSIONS The virtual disappearance of vaccine serotypes in S pneumoniae carriage has occurred in young children, with rapid replacement with penicillin-nonsusceptible nonvaccine serotypes, particularly 19A and 35B. Except for the age group at highest risk, previous predictors of carriage, such as child care attendance and the presence of young siblings, have not been changed by the vaccine. PMID:19564254

  14. 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.

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

    Science.gov (United States)

    Leite, Carolina Regis; Azevedo, Jailton; Galvão, Vivian Santos; Moreno-Carvalho, Otávio; Reis, Joice Neves; Nascimento-Carvalho, Cristiana

    2016-01-01

    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%), 18C (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.

  16. Childhood meningitis in the conjugate vaccine era: a prospective cohort study.

    Science.gov (United States)

    Sadarangani, Manish; Willis, Louise; Kadambari, Seilesh; Gormley, Stuart; Young, Zoe; Beckley, Rebecca; Gantlett, Katherine; Orf, Katharine; Blakey, Sarah; Martin, Natalie G; Kelly, Dominic F; Heath, Paul T; Nadel, Simon; Pollard, Andrew J

    2015-03-01

    Bacterial conjugate vaccines have dramatically changed the epidemiology of childhood meningitis; viral causes are increasingly predominant, but the current UK epidemiology is unknown. This prospective study recruited children under 16 years of age admitted to 3 UK hospitals with suspected meningitis. 70/388 children had meningitis-13 bacterial, 26 viral and 29 with no pathogen identified. Group B Streptococcus was the most common bacterial pathogen. Infants under 3 months of age with bacterial meningitis were more likely to have a reduced Glasgow Coma Score and respiratory distress than those with viral meningitis or other infections. There were no discriminatory clinical features in older children. Cerebrospinal fluid (CSF) white blood cell count and plasma C-reactive protein at all ages, and CSF protein in infants meningitis and viral meningitis or other infections. Improved diagnosis of non-bacterial meningitis is urgently needed to reduce antibiotic use and hospital stay.

  17. An innovative method for quality control of conjugated Haemophilus influenzae vaccines: A short review of two-dimensional nanoparticle electrophoresis.

    Science.gov (United States)

    Tietz, Dietmar

    2009-12-25

    This article provides an overview of a 2D agarose electrophoretic procedure for the characterization of semi-synthetic Haemophilus influenzae type b meningitis vaccines that were prepared for the immunization of small children. The analysis of such vaccines has been particularly challenging because the vaccine particles (i) are highly negatively charged, (ii) are as large as or even larger than intact viruses, and (iii) have a continuous (polydisperse) size distribution because of randomizing steps in the vaccine production (sonification and crosslinking). As a result of these characteristics, 1D electrophoresis of the vaccines produced smears without discernable peaks, but with a second dimension of separation a characteristic vaccine fingerprint was obtained. Whereas O'Farrell gels can accomplish a 2D separation according to size and charge for samples with protein-sized particles, nondenaturing 2D agarose electrophoresis achieves a similar result for much larger virus-sized particles. The separation principle, however, is different. Even though the 2D electrophoretic method was developed from 1983 to 1995, it remains a promising tool for vaccine quality control and for predicting vaccine effectiveness. Modern technology makes the analysis significantly more practical and affordable than it was more than 10 years ago, and the method is applicable to a variety of conjugated vaccines and complex mixtures of virus-sized particles.

  18. Pneumococcal Carriage and Antibiotic Resistance in Young Children before 13-Valent Conjugate Vaccine

    Science.gov (United States)

    WROE, PETER C.; LEE, GRACE M.; FINKELSTEIN, JONATHAN A.; PELTON, STEPHEN I.; HANAGE, WILLIAM P.; LIPSITCH, MARC; STEVENSON, ABBIE E.; RIFAS-SHIMAN, SHERYL L.; KLEINMAN, KEN; DUTTA-LINN, M. MAYA; HINRICHSEN, VIRGINIA L.; LAKOMA, MATTHEW; HUANG, SUSAN S.

    2012-01-01

    Background We sought to measure trends in Streptococcus pneumoniae (SP) carriage and antibiotic resistance in young children in Massachusetts communities after widespread adoption of heptavalent pneumococcal conjugate vaccine (PCV7) and before the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13). Methods We conducted a cross-sectional study including collection of questionnaire data and nasopharyngeal specimens among children <7 years in primary care practices from 8 Massachusetts communities during the winter season of 2008–9 and compared with to similar studies performed in 2001, 2003–4, and 2006–7. Antimicrobial susceptibility testing and serotyping were performed on pneumococcal isolates, and risk factors for colonization in recent seasons (2006–07 and 2008–09) were evaluated. Results We collected nasopharyngeal specimens from 1,011 children, 290 (29%) of whom were colonized with pneumococcus. Non-PCV7 serotypes accounted for 98% of pneumococcal isolates, most commonly 19A (14%), 6C (11%), and 15B/C (11%). In 2008–09, newly-targeted PCV13 serotypes accounted for 20% of carriage isolates and 41% of penicillin non-susceptible S. pneumoniae (PNSP). In multivariate models, younger age, child care, young siblings, and upper respiratory illness remained predictors of pneumococcal carriage, despite near-complete serotype replacement. Only young age and child care were significantly associated with PNSP carriage. Conclusions Serotype replacement post-PCV7 is essentially complete and has been sustained in young children, with the relatively virulent 19A being the most common serotype. Predictors of carriage remained similar despite serotype replacement. PCV13 may reduce 19A and decrease antibiotic-resistant strains, but monitoring for new serotype replacement is warranted. PMID:22173142

  19. Humoral and cell-mediated immunity following vaccination with synthetic Candida cell wall mannan derived heptamannoside-protein conjugate: immunomodulatory properties of heptamannoside-BSA conjugate.

    Science.gov (United States)

    Paulovičová, Lucia; Paulovičová, Ema; Karelin, Alexander A; Tsvetkov, Yury E; Nifantiev, Nikolay E; Bystrický, Slavomír

    2012-10-01

    Chemically defined glycoprotein conjugate composed of synthetically prepared mannan-derived heptamannoside with terminal β-1,2-linked mannose residue attached to the α-1,3-linked mannose residues and BSA as carrier protein (M7-BSA conjugate) was analysed for the capacity to induce protective humoral immunity and appropriate alteration cellular immunity. To identify protective antigenic structure of Candida cell wall mannan M7-BSA conjugate was used for BALB/c mice immunization. The obtained results were compared with placebo group and with heat-inactivated C. albicans whole cells immunization. The administration route of M7-BSA conjugate secondary booster injection significantly affected the intensity of humoral immune response and the specificity of produced antibodies. All prepared sera were able to elevate candidacidal activity of polymorphonuclear leukocytes (PMN) in cooperation with complement. Moreover, polyclonal sera obtained after secondary subcutaneous (s.c.) booster injection of M7-BSA conjugate were able to induce candidacidal activity of PMN also in complement independent manner. M7-BSA conjugate immunization induced increases of phagocytic activity and respiratory burst of granulocytes, caused a raise of the proportion of CD3(+) T lymphocytes and increased the CD4(+)/CD8(+) T lymphocyte ratio. We observed also an increasing proportion of CD4(+)CD25(+) T cells compared to immunization with heat inactivated whole C. albicans cells, which in turn promoted an increase of the CD8(+)CD25(+) cell proportion. Immunization with M7-BSA conjugate induced Th1, Th2 and Th17 immune responses as indicated by the elevation of relevant cytokines levels. These data provide some insights on the immunomodulatory properties of oligomannosides and contribute to the development of synthetic oligosaccharide vaccines against fungal diseases.

  20. Meningococcal serogroup A, C, W₁₃₅ and Y conjugated vaccine: a cost-effectiveness analysis in the Netherlands.

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    Hiltsje Hepkema

    Full Text Available BACKGROUND: In 2002, vaccination with a serogroup C meningococcal conjugate vaccine (MenC was introduced in the Netherlands for all children aged 14 months. Despite its success, herd immunity may wane over time. Recently, a serogroup A,C,W135,Y meningococcal conjugate vaccine (MenACWY was licensed for use in subjects of 12 months of age and above. OBJECTIVES: To evaluate the cost-effectiveness of meningococcal vaccination at 14 months and an additional vaccination at the age of 12 years, both with the MenACWY vaccine. METHODS: A decision analysis cohort model, with 185,000 Dutch newborns, was used to evaluate the cost-effectiveness of different immunization strategies. For strategies including a vaccination at 12 years of age, an additional cohort with adolescents aged 12 years was followed. The incremental cost-effectiveness ratio (ICER was estimated for the current disease incidence and for a scenario when herd immunity is lost. RESULTS: Vaccination with MenACWY at 14 months is cost-saving. Vaccinating with MenACWY at 14 months and at 12 years would prevent 7 additional cases of meningococcal serogroup A,C,W135,Y disease in the birth cohort and adolescent cohort followed for 99 years compared to the current vaccine schedule of a single vaccination with MenC at 14 months. With the current incidence, this strategy resulted in an ICER of €635,334 per quality adjusted life year. When serogroup C disease incidence returns to pre-vaccination levels due to a loss of vaccine-induced herd-immunity, vaccination with MenACWY at 14 months and at 12 years would be cost-saving. CONCLUSIONS: Routine vaccination with MenACWY is cost-saving. With the current epidemiology, a booster-dose with MenACWY is not likely cost-effective. When herd immunity is lost, a booster-dose has the potential of being cost-effective. A dynamic model should be developed for more precise estimation of the cost-effectiveness of the prevention of disappearance of herd immunity.

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

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    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.

  2. High nasopharyngeal carriage of non-vaccine serotypes in Western Australian aboriginal people following 10 years of pneumococcal conjugate vaccination.

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    Deirdre A Collins

    Full Text Available BACKGROUND: Invasive pneumococcal disease (IPD continues to occur at high rates among Australian Aboriginal people. The seven-valent pneumococcal conjugate vaccine (7vPCV was given in a 2-4-6-month schedule from 2001, with a 23-valent pneumococcal polysaccharide vaccine (23vPPV booster at 18 months, and replaced with 13vPCV in July 2011. Since carriage surveillance can supplement IPD surveillance, we have monitored pneumococcal carriage in western Australia (WA since 2008 to assess the impact of the 10-year 7vPCV program. METHODS: We collected 1,500 nasopharyngeal specimens from Aboriginal people living in varied regions of WA from August 2008 until June 2011. Specimens were cultured on selective media. Pneumococcal isolates were serotyped by the quellung reaction. RESULTS: Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis were carried by 71.9%, 63.2% and 63.3% respectively of children <5 years of age, and 34.6%, 22.4% and 27.2% of people ≥5 years. Of 43 pneumococcal serotypes identified, the most common were 19A, 16F and 6C in children <5 years, and 15B, 34 and 22F in older people. 7vPCV serotypes accounted for 14.5% of all serotypeable isolates, 13vPCV for 32.4% and 23vPPV for 49.9%, with little variation across all age groups. Serotypes 1 and 12F were rarely identified, despite causing recent IPD outbreaks in WA. Complete penicillin resistance (MIC ≥2µg/ml was found in 1.6% of serotype 19A (5.2%, 19F (4.9% and 16F (3.2% isolates and reduced penicillin susceptibility (MIC ≥0.125µg/ml in 24.9% of isolates, particularly 19F (92.7%, 19A (41.3%, 16F (29.0%. Multi-resistance to cotrimoxazole, tetracycline and erythromycin was found in 83.0% of 23F isolates. Among non-serotypeable isolates 76.0% had reduced susceptibility and 4.0% showed complete resistance to penicillin. CONCLUSIONS: Ten years after introduction of 7vPCV for Aboriginal Australian children, 7vPCV serotypes account for a small proportion of carried

  3. Impact of 13-Valent Pneumococcal Conjugate Vaccination on Streptococcus pneumoniae Carriage in Young Children in Massachusetts

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    Lee, Grace M.; Kleinman, Ken; Pelton, Stephen I.; Hanage, William; Huang, Susan S.; Lakoma, Matthew; Dutta-Linn, Maya; Croucher, Nicholas J.; Stevenson, Abbie; Finkelstein, Jonathan A.

    2014-01-01

    Background In April 2010, a 13-valent pneumococcal conjugate vaccine (PCV13) replaced PCV7 for use in the United States. We evaluated rates of pneumococcal colonization, by serotype and antibiotic resistance, in Massachusetts communities where serial cross-sectional surveillance has been conducted for the past decade. Methods Nasopharyngeal swabs were obtained from children 0 to <7 years of age and seen by primary care providers for well child or acute illness visits in 2001, 2004, 2007, 2009, and 2011. Pneumococcal isolates were serotyped by Quellung reaction and classified as PCV7 serotypes (4, 6B, 9V, 14, 18C, 19F, 23F), additional PCV13 serotypes (1, 3, 5, 6A, 7F, 19A), or non-PCV13 serotypes. Changes in colonization and impact of PCV13 were assessed using generalized linear mixed models, adjusting for known risk factors and accounting for clustering by community. Results Introduction of PCV13 did not affect the rate of overall pneumococcal colonization (31% in 2011). Colonization with non-PCV13 serotypes increased between 2001 and 2011 for all children (odds ratio [OR] per year, 1.12; 95% confidence interval [CI], 1.10, 1.15; P < .0001). 19A remained the second most common serotype in 2011, although a decline from 2009 was observed. Penicillin (7%), erythromycin (28%), ceftriaxone (10%), and clindamycin (10%) nonsusceptibility were commonly identified, concentrated among a small number of serotypes (including 19A, 35B, 15B/C, and 15A). Among healthy children 6–23 months old, colonization with PCV13 serotypes was lower among recipients of PCV13 vaccine (adjusted OR, 0.30; 95% CI, 0.11, 0.78). This effect was not observed in 6- to 23-month-old children with a concomitant respiratory tract infection (adjusted OR 1.36; 95% CI, 0.66, 2.77) or children 2 to <7 years old (adjusted OR, 1.17; 95% CI, 0.58, 2.34). Conclusions 13-Valent pneumococcal conjugate vaccine reduced the prevalence of colonization with PCV13 serotypes among children 6–23 months old, but its

  4. Moderate PEGylation of the carrier protein improves the polysaccharide-specific immunogenicity of meningococcal group A polysaccharide conjugate vaccine.

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    Zhang, Tingting; Yu, Weili; Wang, Yanfei; Hu, Tao

    2015-06-22

    Neisseria meningitidis can cause severe and fulminant diseases such as meningitis. Meningococcal capsular polysaccharide (PS) is a key virulence determinant that is not able to induce immunological memory. Conjugation of PS to a carrier protein can significantly increase the immunogenicity of PS and induce immunological memory. Due to the classically described carrier-induced epitopic suppression (CIES) mechanisms, a strong immune response against the carrier protein could suppress the immune response to PS after coadministration of free carrier protein with the conjugate vaccine. However, it was not clear whether suppressing or enhancing the protein-specific immunogenicity could improve the PS-specific immunogenicity of the conjugate vaccine. Thus, moderate PEGylation, extensive PEGylation and oligomerization were used to regulate the immunogenicity of tetanus toxoid (TT) in the conjugate vaccine (PS-TT). Moderate PEGylation led to a 2.7-fold increase in the PS-specific IgG titers elicited by PS-TT. In contrast, extensive PEGylation and oligomerization of TT led to 1.4-fold and 1.6-fold decrease in the PS-specific IgG titers elicited by PS-TT, respectively. The PS-specific immunogenicity of PS-TT can be increased by moderate PEGylation through mild suppression of the TT-specific immunogenicity. The PS-specific immunogenicity of PS-TT was decreased through significant suppression or enhancement of the TT-specific immunogenicity. Thus, our study contributes to understand the CIES mechanisms and improve the PS-specific immunogenicity of a meningococcal PS conjugate vaccine.

  5. Effects of an oxycodone conjugate vaccine on oxycodone self-administration and oxycodone-induced brain gene expression in rats.

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    Marco Pravetoni

    Full Text Available Prescription opioid abuse is an increasing public health concern in the USA. A vaccine comprising a hapten (OXY conjugated to the carrier protein keyhole limpet hemocyanin (OXY-KLH has been shown to attenuate the antinociceptive effects of oxycodone. Here, the vaccine's ability to prevent acquisition of intravenous (i.v. oxycodone self-administration was studied in rats. Effects of vaccination on oxycodone-induced changes in the expression of several genes within the mesolimbic system, which are regulated by chronic opiate use, were also examined. Vaccination with OXY-KLH reduced the proportion of rats acquiring i.v. self-administration of oxycodone under a fixed ratio (FR 3 schedule of reinforcement compared to control rats immunized with the unconjugated KLH carrier protein. Vaccination significantly reduced the mean number of infusions at FR3, total number of infusions, and total oxycodone intake during the entire protocol. Compared to oxycodone self-administering control rats immunized with the carrier alone, rats vaccinated with the OXY-KLH immunogen showed increased levels of adenylate cyclase 5 (Adcy5 and decreased levels of early growth response protein 2 (Egr2 and the early immediate gene c-Fos in the striatum. These data suggest that vaccination with OXY-KLH can attenuate the reinforcing effects of oxycodone at a clinically-relevant exposure level. Analysis of mRNA expression identified some addiction-relevant markers that may be of interest in understanding oxycodone effects or the protection provided by vaccination.

  6. Characterization and optimization of heroin hapten-BSA conjugates: method development for the synthesis of reproducible hapten-based vaccines.

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    Torres, Oscar B; Jalah, Rashmi; Rice, Kenner C; Li, Fuying; Antoline, Joshua F G; Iyer, Malliga R; Jacobson, Arthur E; Boutaghou, Mohamed Nazim; Alving, Carl R; Matyas, Gary R

    2014-09-01

    A potential new treatment for drug addiction is immunization with vaccines that induce antibodies that can abrogate the addictive effects of the drug of abuse. One of the challenges in the development of a vaccine against drugs of abuse is the availability of an optimum procedure that gives reproducible and high yielding hapten-protein conjugates. In this study, a heroin/morphine surrogate hapten (MorHap) was coupled to bovine serum albumin (BSA) using maleimide-thiol chemistry. MorHap-BSA conjugates with 3, 5, 10, 15, 22, 28, and 34 haptens were obtained using different linker and hapten ratios. Using this optimized procedure, MorHap-BSA conjugates were synthesized with highly reproducible results and in high yields. The number of haptens attached to BSA was compared by 2,4,6-trinitrobenzenesulfonic acid (TNBS) assay, modified Ellman's test and matrix assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). Among the three methods, MALDI-TOF MS discriminated subtle differences in hapten density. The effect of hapten density on enzyme-linked immunosorbent assay (ELISA) performance was evaluated with seven MorHap-BSA conjugates of varying hapten densities, which were used as coating antigens. The highest antibody binding was obtained with MorHap-BSA conjugates containing 3-5 haptens. This is the first report that rigorously analyzes, optimizes and characterizes the conjugation of haptens to proteins that can be used for vaccines against drugs of abuse. The effect of hapten density on the ELISA detection of antibodies against haptens demonstrates the importance of careful characterization of the hapten density by the analytical techniques described.

  7. 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......, 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....... The administration of PCV7 was followed by a marked decline in the incidence of IPD in both vaccinated and non-vaccinated individuals....

  8. The impact of B-cell perturbations on pneumococcal conjugate vaccine response in HIV-infected adults.

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    Johannesson, Thomas G; Søgaard, Ole S; Tolstrup, Martin; Petersen, Mikkel S; Bernth-Jensen, Jens M; Østergaard, Lars; Erikstrup, Christian

    2012-01-01

    Untreated HIV infection results in severe perturbations of the B-cell population and hyporesponsiveness to vaccination. We studied associations between circulating B-cell subsets and antibody response to pneumococcal conjugate vaccine in treated and untreated HIV patients.Ninety-five HIV-infected adults were grouped according to antiretroviral therapy (ART) and CD4+ cell count as follows: 20 ART-naïve (no prior ART), 62 ART-responders (received ART, and CD4 count >500 cells/µl), and 13 impaired responders (received ART for more than 3 years, and CD4 count CPG 7909 (toll-like receptor 9 agonist) at baseline and after three months. Pre-vaccination B-cell subpopulations were assessed by flow cytometry. Serum IgG concentrations for vaccine serotypes were quantified by ELISA at baseline and 3, 4, and 9 months post-vaccination. ART responders had more isotype-switched memory B cells and more marginal-zone (MZ)-like B cells compared with impaired responders. Furthermore, ART-naïve patients had higher concentration of transitional B cells and plasmablasts compared with B cells of other patient groups. The concentration of MZ-like, isotype switched memory cells and plasmablasts correlated positively with post-vaccination IgG concentration at 3, 4, and 9 months. Low concentrations of isotype-switched memory B cells was the strongest independent predictor of poor pneumococcal conjugate vaccine responsiveness, emphasizing that B-cell subset disturbances are associated with poor vaccine response among HIV-infected patients.

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

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    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 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 (pmedia 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.

  10. Safety and preliminary immunogenicity of Cuban pneumococcal conjugate vaccine candidate in healthy children: a randomized phase I clinical trial.

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    Dotres, Carlos P; Puga, Rinaldo; Ricardo, Yariset; Broño, Carmen R; Paredes, Beatriz; Echemendía, Vladimir; Rosell, Sandra; González, Nadezhda; García-Rivera, Dagmar; Valdés, Yury; Goldblatt, David; Vérez-Bencomo, Vicente

    2014-09-15

    A new heptavalent conjugate vaccine (PCV7-TT) is under development in Cuba. PCV7-TT contains 2 μg of serotypes 1, 5, 14, 18C, 19F, 23F and 4 μg of 6B, each one conjugated to tetanus toxoid (TT). This vaccine was designed with the serotypes that cause most invasive pneumococcal diseases (IPD) worldwide. In the present study, we investigated the safety and explored the immunogenicity of PCV7-TT during a controlled, randomized and double blind clinical trial phase I in 4-5-year-old children. PCV7-TT was well tolerated and as safe as Synflorix used as control vaccine. Following a single-dose vaccination, all individual serotypes included in PCV7-TT induced statistically significant increase of IgG GMC and OPA GMT. These are the first clinical results of PCV7-TT in children and they pave the way toward next clinical trials in children and infants. This clinical trial was published in the Cuban Public Register of Clinical Trials with code RPCEC00000173.

  11. 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?

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    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.

  12. PspA family distribution, unlike capsular serotype, remains unaltered following introduction of the heptavalent pneumococcal conjugate vaccine.

    Science.gov (United States)

    Croney, Christina M; Coats, Mamie T; Nahm, Moon H; Briles, David E; Crain, Marilyn J

    2012-06-01

    Pneumococcal conjugate vaccines (PCVs) are recommended for the prevention of invasive pneumococcal disease (IPD) in young children. Since the introduction of the heptavalent pneumococcal vaccine (PCV7) in 2000, IPD caused by serotypes in the vaccine has almost been eliminated, and previously uncommon capsular serotypes now cause most cases of pediatric IPD in the United States. One way to protect against these strains would be to add cross-reactive protein antigens to new vaccines. One such protein is pneumococcal surface protein A (PspA). Prior to 2000, PspA families 1 and 2 were expressed by 94% of isolates. Because PCV7 vaccine pressure has resulted in IPD caused by capsular serotypes that were previously uncommon and unstudied for PspA expression, it was possible that many of the new strains expressed different PspA antigens or even lacked PspA. Of 157 pediatric invasive pneumococcal isolates collected at a large pediatric hospital in Alabama between 2002 and 2010, only 60.5% had capsular serotypes included in PCV13, which came into general use in Alabama after our strains were collected. These isolates included 17 serotypes that were not covered by PCV13. Nonetheless, pneumococcal capsular serotype replacement was not associated with changes in PspA expression; 96% of strains in this collection expressed PspA family 1 or 2. Continued surveillance will be critical to vaccine strategies to further reduce IPD.

  13. 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...

  14. Effectiveness and cost-effectiveness of general immunisation of infants and young children with the heptavalent conjugated pneumococcal vaccine

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    Stürzlinger, Heidi

    2005-11-01

    Full Text Available Background: The European Agency for the Evaluation of Medicinal Products (EMEA granted market authorisation to the heptavalent pneumococcal vaccine Prevenar (Wyeth in the year 2001. The indication of Prevenar is the active immunisation of infants and young children under the age of two against invasive disease caused by Streptococcus pneumonia serotypes 4, 6B, 9V, 14, 18C, 19F and 23F. At the time of this study the German vaccination scheme advises the immunisation with Prevenar only for children at high risk. Objectives: The objective of the study is first to determine the efficacy and effectiveness of the immunisation of all children with the heptavalent conjugated pneumococcal vaccine in Germany and second, whether a general recommendation for vaccination of all children would be cost-effective. Methods: A systematic literature search was performed in 29 relevant databases for the period of January 1999 to June 2004. Thus 1,884 articles were identified which were then assessed according to predefined selection criteria. Results: There is evidence for the medical effectiveness of Prevenar against invasive pneumococcal disease caused by the covered serotypes from a major double-blinded RCT undertaken in California. The vaccine shows lower values of effectiveness against otitis media and pneumonia. The values for effectiveness of the vaccine in Germany are below the data for California because of the different incidence of Serotypes. The cost-effectiveness rates for an immunisation of all children with Prevenar vary across different countries. One reason - besides different Health Systems - can be seen in the uncertainty about the duration of protection, another in the assumption on regional serotype coverage of the vaccine. From the healthcare payers' perspective a general vaccination of all children in Germany is not cost-effective, from a societal perspective the benefits from vaccination could prevail the cost. The actual price of the

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

    Science.gov (United States)

    Alam, Mohammad Murshid; Bufano, Megan Kelly; Xu, Peng; Kalsy, Anuj; Yu, Y; Freeman, Y Wu; Sultana, Tania; Rashu, Md Rasheduzzaman; Desai, Ishaan; Eckhoff, Grace; Leung, Daniel T; Charles, Richelle C; LaRocque, Regina C; Harris, Jason B; Clements, John D; Calderwood, Stephen B; Qadri, Firdausi; Vann, W F; Kováč, Pavol; Ryan, Edward T

    2014-02-01

    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.

  16. Impact of pneumococcal vaccination in Denmark during the first 3 years after PCV introduction in the childhood immunization programme

    DEFF Research Database (Denmark)

    Ingels, Helene; Rasmussen, Jeppe; Andersen, Peter Henrik

    2012-01-01

    BACKGROUND AND AIMS: The 7-valent pneumococcal conjugate vaccine (PCV7) was introduced in Denmark in October 2007 in a 2+1 schedule with a catch-up programme for children up to 17 months of age. To assess the impact of PCV we evaluated on the whole population: (1) direct and indirect effects...... and of IPD caused by vaccine serotypes declined significantly from 19.5 to 17.7 and from 7.7 to 3.8 cases per 100,000 persons comparing the two periods. The incidence of IPD due to non-vaccine serotypes (NVT-IPD) increased significantly from 11.8 to 13.9 cases per 100,000 in the whole population (incidence...... rate ratio 1.18; 95% CI [1.12-1.24]) with predominance of the serotypes 1.7F and 19A. CONCLUSIONS: We report a marked decline in incidence in IPD in both vaccinated and non-vaccinated age groups and a minor but statistically significant increase in incidence of IPD due to NVTs in both vaccinated...

  17. August 2013 pulmonary journal club: pneumococcal vaccine déjà vu

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    Robbins RA

    2013-08-01

    Full Text Available No abstract available. Article truncated at 150 words. Griffin MR, Zhu Y, Moore MR, Whitney CG, Grijalva CG. U.S. hospitalizations for pneumonia after a decade of pneumococcal vaccination. N Engl J Med. 2013;369(2:155-63. [CrossRef] [PubMed] The introduction of the 7-valent pneumococcal conjugate vaccine (PCV7 into the U.S. childhood immunization schedule in 2000 has substantially reduced the incidence of vaccine-serotype invasive pneumococcal disease in young children and in unvaccinated older children and adults. By preventing the acquisition and carriage of pneumococcus in the nasopharynx of vaccinated children, PCV7 reduced the transmission of vaccine serotypes to the unvaccinated. The authors estimated the annual rates of hospitalization for pneumonia from any cause using the Nationwide Inpatient Sample database. Average annual rates of pneumonia-related hospitalizations from 1997 through 1999 (before the introduction of PCV7 and from 2007 through 2009 (well after its introduction were used to estimate annual declines in hospitalizations due to pneumonia. The annual rate of hospitalization for pneumonia among …

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

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    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.

  19. Immunogenicity and Safety of the 13-Valent Pneumococcal Conjugate Vaccine versus the 23-Valent Polysaccharide Vaccine in Unvaccinated HIV-Infected Adults: A Pilot, Prospective Controlled Study.

    Directory of Open Access Journals (Sweden)

    Francesca Lombardi

    Full Text Available Definition of the optimal pneumococcal vaccine strategy in HIV-infected adults is still under evaluation. We aimed to compare immunogenicity and safety of the 13-valent pneumococcal conjugate vaccine (PCV13 versus the 23-valent polysaccharide vaccine (PPSV23 in HIV-infected adults.We performed a pilot, prospective controlled study enrolling HIV-infected pneumococcal vaccine-naïve outpatients, aged 18-65 years with CD4 counts ≥200 cells/μL. Eligible subjects were recruited into two parallel groups: group 1 (n = 50 received two doses of PCV13 eight weeks apart, and group 2 (n = 50 received one dose of PPSV23, as part of their standard of care. Anti-pneumococcal capsular polysaccharide immunoglobulin G concentrations were quantified by ELISA at baseline, 8, 24 and 48 weeks. Clinical and viro-immunological follow-up was performed at the same time points. Unvaccinated, age-matched HIV-negative adults (n = 100 were also enrolled as baseline controls.Pre-vaccination specific IgG titers for each pneumococcal antigen did not differ between study groups but they were constantly lower than those from the HIV-negative controls. After immunization, significant increases in IgG titers were observed in both study groups at each time point compared to baseline, but response to serotype 3 was blunted in group 1. Antibody titers for each antigen did not differ between study groups at week 48. Overall, the proportion of subjects achieving seroprotection and seroconversion to all serotypes was comparable between groups. A marked decrease in IgG levels over time was observed with both vaccines. No relevant adverse reactions were reported in either group.In this population with favorable immune profile, no relevant differences were observed in immunogenicity between PCV13 and PPSV23. Both vaccines were safe and well tolerated.ClinicalTrials.gov NCT02123433.

  20. 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.

  1. 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.

  2. 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

    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......SC peaked early (day 7) had higher prevaccination anti-DT levels than those who peaked later (P less than 0.05). In contrast, the prevaccination levels of anti-PRP did not correlate significantly with the magnitude of the antibody or AbSC response and did not affect the kinetics of the AbSC. Following...

  3. Streptococcus pneumoniae serotype distribution in Vojvodina before the introduction of pneumococcal conjugate vaccines into the national immunization program

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    Petrović Vladimir

    2016-01-01

    Full Text Available Introduction. Streptococcus pneumoniae is the most common causative agent of bacterial pneumonia and meningitis. Mandatory childhood immunization against pneumococcal diseases is introduced in the new Law on Protection of Population against Communicable Diseases in Serbia. Objective. The objective of this study was to determine the prevalence of pneumococcal serotype distribution in Vojvodina region before routine use of pneumococcal conjugate vaccine in Serbia. Methods. A total of 105 isolates of Streptococcus pneumoniae were collected in the period from January 2009 to April 2016. Based on the results of serotyping in the National Reference Laboratory, we analyzed distribution of circulating serotypes and coverage of conjugate and 23-valent polysaccharide pneumococcal vaccines in different age groups. Results. Among 105 isolates, a total of 21 different serotypes of Streptococcus pneumoniae were determined. The most frequent serotypes were 3 (21.9%, 19F (20.0%, and 14 (10.5%. The serotype coverage of pneumococcal conjugate vaccines (PCV7, PCV10, and PCV13 was 48.6%, 54.3%, and 84.8%, respectively, while pneumococcal polysaccharide vaccine (PPV23 covered 89.5% of the total number of isolates in all age groups. Serotypes included in PCV7, PCV10, and PCV13 represented 72.0%, 76.0%, and 88.0% of the total number of isolates in children ≤5 years, respectively. Vaccine serotype coverage of PCV13 and PPV23 ranged from 87.1% to 90.3% in adults 50-64 years of age, and 77.8% to 85.2% in adults ≥65 years old. Conclusion. Serotype distribution of Streptococcus pneumoniae in the population fairly overlaps with the serotypes contained in pneumococcal vaccines, so that implementation of childhood immunization is justified. The study was done in the Province of Vojvodina but the findings may be applied to Serbia as a whole. [Projekat Ministarstva nauke Republike Srbije, br. ON 175039] This article has been corrected. Link to the correction 10.2298/SARH

  4. Synthesis and evaluation of a conjugate vaccine composed of Staphylococcus aureus poly-N-acetyl-glucosamine and clumping factor A.

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    Tomás Maira-Litrán

    Full Text Available The increasing frequency, severity and antimicrobial resistance of Staphylococcus aureus infections has made the development of immunotherapies against this pathogen more urgent than ever. Previous immunization attempts using monovalent antigens resulted in at best partial levels of protection against S. aureus infection. We therefore reasoned that synthesizing a bivalent conjugate vaccine composed of two widely expressed antigens of S. aureus would result in additive/synergetic activities by antibodies to each vaccine component and/or in increased strain coverage. For this we used reductive amination, to covalently link the S. aureus antigens clumping factor A (ClfA and deacetylated poly-N-β-(1-6-acetyl-glucosamine (dPNAG. Mice immunized with 1, 5 or 10 µg of the dPNAG-ClfA conjugate responded in a dose-dependent manner with IgG to dPNAG and ClfA, whereas mice immunized with a mixture of ClfA and dPNAG developed significantly lower antibody titers to ClfA and no antibodies to PNAG. The dPNAG-ClfA vaccine was also highly immunogenic in rabbits, rhesus monkeys and a goat. Moreover, affinity-purified, antibodies to ClfA from dPNAG-ClfA immune serum blocked the binding of three S. aureus strains to immobilized fibrinogen. In an opsonophagocytic assay (OPKA goat antibodies to dPNAG-ClfA vaccine, in the presence of complement and polymorphonuclear cells, killed S. aureus Newman and, to a lower extent, S. aureus Newman ΔclfA. A PNAG-negative isogenic mutant was not killed. Moreover, PNAG antigen fully inhibited the killing of S. aureus Newman by antisera to dPNAG-ClfA vaccine. Finally, mice passively vaccinated with goat antisera to dPNAG-ClfA or dPNAG-diphtheria toxoid conjugate had comparable levels of reductions of bacteria in the blood 2 h after infection with three different S. aureus strains as compared to mice given normal goat serum. In conclusion, ClfA is an immunogenic carrier protein that elicited anti-adhesive antibodies that fail to

  5. Prevention of pneumococcal diseases in the post-seven valent vaccine era: A European perspective

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    Weil-Olivier Catherine

    2012-09-01

    Full Text Available Abstract Background The burden of invasive pneumococcal disease in young children decreased dramatically following introduction of the 7-valent pneumococcal conjugate vaccine (PCV7. The epidemiology of S. pneumoniae now reflects infections caused by serotypes not included in PCV7. Recently introduced higher valency pneumococcal vaccines target the residual burden of invasive and non-invasive infections, including those caused by serotypes not included in PCV7. This review is based on presentations made at the European Society of Pediatric Infectious Diseases in June 2011. Discussion Surveillance data show increased circulation of the non-PCV7 vaccine serotypes 1, 3, 6A, 6C, 7 F and 19A in countries with routine vaccination. Preliminary evidence suggests that broadened serotype coverage offered by higher valency vaccines may be having an effect on invasive disease caused by some of those serotypes, including 19A, 7 F and 6C. Aetiology of community acquired pneumonia remains a difficult clinical diagnosis. However, recent reports indicate that pneumococcal vaccination has reduced hospitalisations of children for vaccine serotype pneumonia. Variations in serotype circulation and occurrence of complicated and non-complicated pneumonia caused by non-PCV7 serotypes highlight the potential of higher valency vaccines to decrease the remaining burden. PCVs reduce nasopharyngeal carriage and acute otitis media (AOM caused by vaccine serotypes. Recent investigations of the interaction between S. pneumoniae and non-typeable H. influenzae suggest that considerable reduction in severe, complicated AOM infections may be achieved by prevention of early pneumococcal carriage and AOM infections. Extension of the vaccine serotype spectrum beyond PCV7 may provide additional benefit in preventing the evolution of AOM. The direct and indirect costs associated with pneumococcal disease are high, thus herd protection and infections caused by non-vaccine serotypes

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

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    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.

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

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    Miguel Tregnaghi

    2014-09-01

    Conclusions: 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.

  8. Effects of early vaccination with a gonadotropin releasing factor analog-diphtheria toxoid conjugate on boar taint and growth performance of male pigs.

    Science.gov (United States)

    Kantas, D; Papatsiros, V; Tassis, P; Tzika, E; Pearce, M C; Wilson, S

    2014-05-01

    The aim of this study was to evaluate safety (in terms of detecting possible adverse clinical effects attributable to vaccination), efficacy, and effects on growth performance of a gonadotropin releasing factor analog-diphtheria toxoid conjugate (commercially distributed as Improvac; Zoetis, Zaventem, Belgium) in male pigs raised in a commercial Greek farm. A total of 1,230 male pigs was enrolled in 16 weekly batches and allocated to 3 groups: barrows (castrated on the next day after birth [study Day 0]), pigs vaccinated with the above-mentioned product, and intact boars. Vaccinated pigs were injected subcutaneously with 2 mL of the anti-gonadotropin releasing factor (GnRF) vaccine at 9 to 11 wk of age (60-78 d) and 15 to 17 wk of age (102-120 d) and slaughtered at 22 to 25 wk of age (152-176 d). No clinical abnormalities or adverse events attributable to vaccination occurred. Mean BW of vaccinated pigs was 6% greater compared with barrows at slaughter (P vaccinated pigs had greater ADG than barrows from castration to slaughter (8%). In detail, a lower ADG from first to second vaccination (-12%; P vaccination to slaughter (P vaccinated pigs and intact boars was not significantly different throughout the study, except from first to second vaccination (boars greater; P = 0.0059) and second vaccination to slaughter (vaccinates greater; P = 0.0390). Feed conversion ratio of barrows was 11 and 8% greater compared with vaccinated pigs (P = 0.0005) and boars (P = 0.0062) from first to second vaccination but was 23 to 26% lower compared with vaccinated pigs (P vaccination to slaughter and 7 to 9.5% lower from the second vaccination to slaughter (P = 0.0029 and P = 0.0003 for vaccinates and intact boars, respectively). At slaughter, the belly fat androstenone concentration of all vaccinated pigs and 64% of intact boars was below 200 ng/g. Belly fat skatole concentration was below 20 ng/g in samples from all groups. In conclusion, vaccination against GnRF using the Gn

  9. Anti-IgE Qb-VLP Conjugate Vaccine Self-Adjuvants through Activation of TLR7

    Science.gov (United States)

    Akache, Bassel; Weeratna, Risini D.; Deora, Aparna; Thorn, Jennifer M.; Champion, Brian; Merson, James R.; Davis, Heather L.; McCluskie, Michael J.

    2016-01-01

    Qb bacteriophage virus-like particles (Qb-VLP) are utilized as carriers to enhance immune responses to weakly or non-immunogenic antigens such as peptides and haptens. Qb-VLPs are formed through the self-assembly of multiple Qb capsid protein monomers, a process which traps a large amount of bacterial RNA in the core of the VLP. Bacterial RNA is known to activate the innate immune system via TLR 7 and 8 found within the endosomes of certain immune cells and has been shown to contribute to the immunogenicity of Qb-VLP vaccines. Herein, we evaluated an anti-IgE vaccine comprised of two IgE peptides (Y and P) conjugated to Qb-VLP (Qb-Y and Qb-P, respectively) for in vitro stimulation of human PBMCs and in vivo immunogenicity in mice. The in vitro secretion of IFN-α from human PBMCs exposed to Qb-Y is consistent with TLR7 activation. Immunization of mice with the IgE peptide Qb-VLP conjugates induced high titers of anti-IgE antibodies in wild-type mice, but significantly lower titers in TLR7 knockout mice, supporting the self-adjuvanting role of the RNA. Inclusion of alum and alum/CpG as adjuvants partially or completely compensated for the lack of TLR7 activation in TLR7-deficient mice. Our study demonstrates the key role that TLR7 plays in the immunogenicity of the IgE peptide Qb-VLP conjugate vaccine. PMID:26805897

  10. Anti-IgE Qb-VLP Conjugate Vaccine Self-Adjuvants through Activation of TLR7.

    Science.gov (United States)

    Akache, Bassel; Weeratna, Risini D; Deora, Aparna; Thorn, Jennifer M; Champion, Brian; Merson, James R; Davis, Heather L; McCluskie, Michael J

    2016-01-21

    Qb bacteriophage virus-like particles (Qb-VLP) are utilized as carriers to enhance immune responses to weakly or non-immunogenic antigens such as peptides and haptens. Qb-VLPs are formed through the self-assembly of multiple Qb capsid protein monomers, a process which traps a large amount of bacterial RNA in the core of the VLP. Bacterial RNA is known to activate the innate immune system via TLR 7 and 8 found within the endosomes of certain immune cells and has been shown to contribute to the immunogenicity of Qb-VLP vaccines. Herein, we evaluated an anti-IgE vaccine comprised of two IgE peptides (Y and P) conjugated to Qb-VLP (Qb-Y and Qb-P, respectively) for in vitro stimulation of human PBMCs and in vivo immunogenicity in mice. The in vitro secretion of IFN-α from human PBMCs exposed to Qb-Y is consistent with TLR7 activation. Immunization of mice with the IgE peptide Qb-VLP conjugates induced high titers of anti-IgE antibodies in wild-type mice, but significantly lower titers in TLR7 knockout mice, supporting the self-adjuvanting role of the RNA. Inclusion of alum and alum/CpG as adjuvants partially or completely compensated for the lack of TLR7 activation in TLR7-deficient mice. Our study demonstrates the key role that TLR7 plays in the immunogenicity of the IgE peptide Qb-VLP conjugate vaccine.

  11. Anti-IgE Qb-VLP Conjugate Vaccine Self-Adjuvants through Activation of TLR7

    Directory of Open Access Journals (Sweden)

    Bassel Akache

    2016-01-01

    Full Text Available Qb bacteriophage virus-like particles (Qb-VLP are utilized as carriers to enhance immune responses to weakly or non-immunogenic antigens such as peptides and haptens. Qb-VLPs are formed through the self-assembly of multiple Qb capsid protein monomers, a process which traps a large amount of bacterial RNA in the core of the VLP. Bacterial RNA is known to activate the innate immune system via TLR 7 and 8 found within the endosomes of certain immune cells and has been shown to contribute to the immunogenicity of Qb-VLP vaccines. Herein, we evaluated an anti-IgE vaccine comprised of two IgE peptides (Y and P conjugated to Qb-VLP (Qb-Y and Qb-P, respectively for in vitro stimulation of human PBMCs and in vivo immunogenicity in mice. The in vitro secretion of IFN-α from human PBMCs exposed to Qb-Y is consistent with TLR7 activation. Immunization of mice with the IgE peptide Qb-VLP conjugates induced high titers of anti-IgE antibodies in wild-type mice, but significantly lower titers in TLR7 knockout mice, supporting the self-adjuvanting role of the RNA. Inclusion of alum and alum/CpG as adjuvants partially or completely compensated for the lack of TLR7 activation in TLR7-deficient mice. Our study demonstrates the key role that TLR7 plays in the immunogenicity of the IgE peptide Qb-VLP conjugate vaccine.

  12. Advances in pneumococcal vaccines: what are the advantages for the elderly?

    Science.gov (United States)

    Vila-Córcoles, Angel

    2007-01-01

    Streptococcus pneumoniae causes considerable morbidity and mortality in the elderly. There are three established approaches to pneumococcal vaccination: polysaccharide vaccines, protein-polysaccharide conjugate vaccines and protein-based vaccines. This article reviews advances in anti-pneumococcal vaccines, with reference to advantages and shortcomings for the elderly in particular. The 23-valent polysaccharide pneumococcal vaccine (PPV) is currently recommended for high-risk patients and the general elderly population. Although the effectiveness of PPV against pneumonia is unclear, recent studies point to significant protective effects in preventing pneumococcal pneumonia and reducing the severity of disease in vaccinated elderly patients. PPV offers high serotype coverage and, although it is poorly immunogenic in some individuals, provides approximately 60% protection against invasive disease in the general elderly population. PPV vaccination appears cost effective for elderly patients although the vaccine might only be effective in preventing invasive disease. Additional benefits could mean a greater level of vaccine cost effectiveness. However, it is important to understand that PPV provides incomplete protection, especially in those with underlying high-risk conditions, and development of more effective pneumococcal vaccination strategies for elderly patients is still needed. In recent years, the most important advance in the prevention of pneumococcal infections in the elderly has been the introduction of a 7-valent conjugate pneumococcal vaccine (CPV) as a routine vaccination for infants. In addition to dramatically reducing invasive infection in children, CPV has been observed to have a considerable indirect protective effect in parents and grandparents. While the possibility of using CPV in elderly patients has been suggested, currently there are only limited immunogenicity data and no efficacy data in adults. The low serotype coverage is an important

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

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    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.

  14. 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.

  15. Burden of Pneumococcal Disease in Northern Togo before the Introduction of Pneumococcal Conjugate Vaccine

    Science.gov (United States)

    Moïsi, Jennifer C.; Makawa, Makawa-Sy; Tall, Haoua; Agbenoko, Kodjo; Njanpop-Lafourcade, Berthe-Marie; Tamekloe, Stanislas; Amidou, Moussa; Mueller, Judith E.; Gessner, Bradford D.

    2017-01-01

    Background S. pneumoniae is a leading cause of meningitis morbidity and mortality in the African meningitis belt, but little is known of its contribution to the burden of pneumonia in the region. We aimed to estimate the incidence of pneumococcal disease in children and adults in northern Togo, before the introduction of pneumococcal conjugate vaccine (PCV). Methods and findings From May 1st 2010 to April 30th 2013, we systematically enrolled all hospitalized patients meeting a case definition of suspected meningitis or clinical pneumonia, residing in Tone or Cinkasse districts, northern Togo and providing informed consent. We collected clinical data and tested biological specimens according to standardized procedures, including bacteriology and PCR testing of cerebro-spinal fluid for meningitis patients and blood cultures and whole blood lytA PCR for pneumonia patients. Chest X-rays (CXR) were interpreted using the WHO methodology. We included 404 patients with meningitis (104 <5 years of age) and 1550 with pneumonia (251 <5 years) over the study period. Of these, 78 (19%) had pneumococcal meningitis (13 <5 years), 574 (37%) had radiologically-confirmed pneumonia (83 <5 years) and 73 (5%) had culture-confirmed pneumococcal pneumonia (2 <5 years). PCV13 serotypes caused 79% (54/68) of laboratory-confirmed pneumococcal meningitis and 83% (29/35) of culture-confirmed pneumococcal pneumonia. Serotype 1 predominated in meningitis (n = 33) but not in pneumonia patients (n = 1). The incidence of pneumococcal disease was 7.5 per 100,000 among children <5 years of age and 14.8 in persons 5 years of age and above in the study area. When considering CXR-confirmed and blood PCR-positive pneumonia cases as likely pneumococcal, incidence estimates increased to 43.7 and 66.0 per 100,000 in each of these age groups, respectively. Incidence was at least 3-fold higher when we restricted the analysis to the urban area immediately around the study hospitals. Conclusions Our findings

  16. A bivalent conjugate vaccine containing PspA families 1 and 2 has the potential to protect against a wide range of Streptococcus pneumoniae strains and Salmonella Typhi.

    Science.gov (United States)

    Kothari, Neha; Kothari, Sudeep; Choi, Young Joo; Dey, Ayan; Briles, David E; Rhee, Dong Kwon; Carbis, Rodney

    2015-02-04

    Previously we showed that conjugation of pneumococcal surface protein A (PspA) to Vi capsular polysaccharide from Salmonella Typhi enhanced the anti-PspA response without the need to add adjuvant. In the current study conjugates consisting of the α helical regions of PspA families 1 or 2 bound to Vi were used to vaccinate mice to test their ability to protect against a lethal intravenous challenge of a range of various strains of Streptococcus pneumoniae. Conjugate vaccine containing PspA family 1 provided good protection from PspA family 1 challenge strains but offered very little protection against PspA family 2 challenge strains. Similarly, PspA family 2 conjugates provided good protection from PspA family 2 challenge strains and poor protection against PspA family 1 challenge strains. This observation was supported by the low levels of cross-reactivity of PspA antibodies seen in ELISA plates coated with the heterologous PspA family. Cytokine profiles showed a mixed Th1/Th2 response to Vi and the Vi-PspA conjugates. IgG subclass analysis of the anti-Vi response showed a shift from predominantly IgG2a/3 to IgG1 after conjugation to PspA was consistent with other polysaccharide conjugate vaccines. The results demonstrate that conjugation of the α helical region of PspA to Vi enhances its capacity to induce a protective immune response and that a vaccine based on the α helical region of PspA should contain PspA from both families 1 and 2 to achieve broad cross-protection.

  17. Vaccination Coverage and Compliance with Three Recommended Schedules of 10-Valent Pneumococcal Conjugate Vaccine during the First Year of Its Introduction in Brazil: A Cross-Sectional Study.

    Directory of Open Access Journals (Sweden)

    Fabricia Oliveira Saraiva

    Full Text Available Pneumococcal 10-valent conjugate vaccine (PCV10 was introduced to Brazil's National Immunization Program (NIP in 2010. During the first year of vaccine introduction three schedules were used to deal with age at initiation of PCV for catch-up purposes: 3 primary doses + 1 booster (for children aged ≤6 months, a catch-up schedule of 2 doses + 1 booster (7-11 months, and a catch-up schedule of a single dose (12-15 months. The purpose of this study was to assess the magnitude and associated risk factors for under-vaccination or lack of on time vaccination six to eight months after PCV10 introduction. A household survey was conducted in the municipality of Goiania with 1,237 children, who were retroactively classified into one of three age groups, as a factor of the child's age relatively to 30 days after PCV10 introduction. Socioeconomic characteristics and vaccination dates were obtained during home interviews. Vaccination coverage was defined as the percentage of children who completed the recommended number of doses. Compliance with recommended schedules was defined as the percentage of children who received all valid doses at the NIP recommended time interval. Adjusted prevalence ratios (PR of variables independently associated with coverage and compliance were estimated by log binomial regression. Coverage of DTP-Hib was used for comparison purposes. Overall, vaccination coverage was 54.6% (95% CI 52.1-57.7%, lower than DTP-Hib coverage (93.0%; 95% CI 91.5-94.3%. Compliance with recommended schedules was 16.8% (95% CI: 14.7-18.6%. Children 7-11 months old had lower coverage (40.7% and compliance (6.3% compared to children aged 12-15 months (coverage: 88.8%; compliance: 35.6% and ≤6 months old (coverage: 54%; compliance: 18.8%. Having private health insurance was associated with higher PCV10 coverage (PR=1.25; 95% CI: 1.06-1.47, p=0.007, and compliance (PR=1.09; 95% CI: 1.02-1.16, p=0.015. Although PCV10 coverage rapidly increased shortly

  18. 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......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)...

  19. The Positive Correlation of the Enhanced Immune Response to PCV2 Subunit Vaccine by Conjugation of Chitosan Oligosaccharide with the Deacetylation Degree

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    Guiqiang Zhang

    2017-07-01

    Full Text Available Chitosan oligosaccharides (COS, the degraded products of chitosan, have been demonstrated to have versatile biological functions. In primary studies, it has displayed significant adjuvant effects when mixed with other vaccines. In this study, chitosan oligosaccharides with different deacetylation degrees were prepared and conjugated to porcine circovirus type 2 (PCV2 subunit vaccine to enhance its immunogenicity. The vaccine conjugates were designed by the covalent linkage of COSs to PCV2 molecules and administered to BALB/c mice three times at two-week intervals. The results indicate that, as compared to the PCV2 group, COS–PCV2 conjugates remarkably enhanced both humoral and cellular immunity against PCV2 by promoting lymphocyte proliferation and initiating a mixed T-helper 1 (Th1/T-helper 2 (Th2 response, including raised levels of PCV2-specific antibodies and an increased production of inflammatory cytokines. Noticeably, with the increasing deacetylation degree, the stronger immune responses to PCV2 were observed in the groups with COS-PCV2 vaccination. In comparison with NACOS (chitin oligosaccharides–PCV2 and LCOS (chitosan oligosaccharides with low deacetylation degree–PCV2, HCOS (chitosan oligosaccharides with high deacetylation degree–PCV2 showed the highest adjuvant effect, even comparable to that of PCV2/ISA206 (a commercialized adjuvant group. In summary, COS conjugation might be a viable strategy to enhance the immune response to PCV2 subunit vaccine, and the adjuvant effect was positively correlated with the deacetylation degree of COS.

  20. Development of approaches to a third-generation carbohydrate-conjugate vaccine against Streptococcus pneumoniae: the search for optimal oligosaccharide ligands

    Science.gov (United States)

    Gening, M. L.; Kurbatova, E. A.; Tsvetkov, Yu E.; Nifantiev, N. E.

    2015-11-01

    The review addresses the application of synthetic oligosaccharides related to fragments of capsular polysaccharides from different serotypes of the bacterium Streptococcus pneumoniae for the design of third-generation pneumococcal conjugate vaccines. Special focus is given to characteristic features of the chemical structures of oligosaccharides required for the induction of the protective immune response when using synthetic glycoconjugate vaccines based on oligosaccharide ligands and carrier proteins. The bibliography includes 101 references.

  1. Systematic review of economic evaluations of vaccination programs in mainland China: Are they sufficient to inform decision making?

    Science.gov (United States)

    Pan, Xiong-Fei; Griffiths, Ulla K; Pennington, Mark; Yu, Hongjie; Jit, Mark

    2015-11-17

    The purpose of the study was to systematically review economic evaluations of vaccine programs conducted in mainland China. We searched for economic evaluations of vaccination in China published prior to August 3, 2015 in eight English-language and three Chinese-language databases. Each article was appraised against the 19-item Consensus on Health Economic Criteria list (CHEC-list). We found 23 papers evaluating vaccines against hepatitis B (8 articles), Streptococcus pneumoniae (5 articles), human papillomavirus (3 articles), Japanese encephalitis (2 articles), rotavirus (2 articles), hepatitis A (1 article), Enterovirus 71 (1 article) and influenza (1 article). Studies conformed to a mean of 12 (range: 6-18) items in the CHEC-list criteria. Five of six Chinese-language articles conformed to fewer than half of the 19 criteria items. The main criteria that studies failed to conform to included: inappropriate measurement (20 articles) and valuation (18 articles) of treatment and/or vaccination costs, no discussion about distributional implications (18 articles), missing major health outcomes (14 articles), no discussion about generalizability to other contexts (14 articles), and inadequate sensitivity analysis (13 articles). In addition, ten studies did not include major cost components of vaccination programs, and nine did not report outcomes in terms of life years even in cases where QALYs or DALYs were calculated. Only 13 studies adopted a societal perspective for analysis. All studies concluded that the appraised vaccination programs were cost-effective except for one evaluation of universal 7-valent pneumococcal conjugate vaccine (PCV-7) in children. However, three of the five studies on PCV-7 showed poor overall quality, and the number of studies on vaccines other than hepatitis B vaccine and PCV-7 was limited. In conclusion, major methodological flaws and reporting problems exist in current economic evaluations of vaccination programs in China. Local

  2. Occurrence of Haemophilus influenzae strains in three Brazilian states since the introduction of a conjugate Haemophilus influenzae type b vaccine

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    A.E.C.C. de Almeida

    2005-05-01

    Full Text Available Few vaccines in history have induced such a dramatic decline in incidence over such a short period of time as the Haemophilus influenzae type b (Hib conjugate. This vaccine was introduced in 1988 in the United States, but only in 1999 was Hib immunization introduced by the Brazilian Ministry of Health as part of the routine infant National Immunization Program. The authors analyzed 229 H. influenzae (Hi isolates from Public Health Laboratories in three Brazilian states: Pernambuco (Northeast, N = 54, Santa Catarina (South, N = 19, and Rio de Janeiro (Southeast, N = 156. The isolates were collected from Brazilian children 0-10 years of age with meningitis and other infections from 1990 to 2003 and were part of the research collection of the National Institute of Quality Control in Health, FIOCRUZ. Bacterial strains were characterized by serotyping and biotyping. During the pre-vaccination period the prevalence infection due to Hib was of 165 isolates and only 2 non-b Hi among all the notified meningitis infections caused by Hi. Our results showed a significant decrease in the prevalence of Hib meningitis from 165 to 33 isolates after 1999. However, during the post-vaccination period of 2001-2003 we observed an increase in the number of non-b Hi isolates: only 2 non-b strains isolated from 1990 to 1999 and 29 from 1999 to 2003. Based on the present data, the authors emphasize the need for more sensitive epidemiological and bacteriological studies aiming the improvement of the available Hib vaccine, in order to protect the susceptible population to infections due to other serological types of Hi and the reevaluation of immunization schedules used by the National Immunization Program.

  3. Antibiotic susceptibility rates of invasive pneumococci before and after the introduction of pneumococcal conjugate vaccination in Germany.

    Science.gov (United States)

    Imöhl, Matthias; Reinert, Ralf René; van der Linden, Mark

    2015-10-01

    Continuous nationwide surveillance of invasive pneumococcal disease (IPD) was conducted in Germany. A total of 22,208 isolates from invasive pneumococcal disease were collected between July 1, 1992 and June 30, 2013. The present study was conducted to analyze changes in antimicrobial susceptibility and pneumococcal vaccine coverage after the introduction of pneumococcal conjugate vaccination in Germany. Most of the isolates originated from adults ≥16 years (82.5%), while 17.5% were obtained from children resistance was observed in 7.2% of meningitis cases both among children and adults during the entire study period. In the post-PCV13 period, the resistance rate was 11.3% in children and 10.0% in adults, which is higher than in the pre-PCV7 and post-PCV7 periods. In the non-meningitis group, an overall penicillin nonsusceptibility rate (intermediate resistance and resistance) of 0.5% was detected both among children and adults. Nonsusceptibility rates among children were 6.3% (pre-PCV7), 7.6% (post-PCV7) and 9.0% (post-PCV13). The corresponding nonsusceptibility rates among adults were 4.4%, 6.0% and 7.9%, respectively. Concerning cefotaxime, in meningitis cases 0.8% of all isolates were intermediate and 0.5% resistant among children, while among adults, 0.9% were intermediate and 0.2% resistant. In non meningitis cases, cefotaxime nonsusceptibility rates were 0.5% in children and 0.3% in adults. Macrolide nonsusceptibility rates were lower in the post-PCV13 period (children 8.2%; adults 8.8%) than in the post-PCV7 period (children 17.3%; adults 13.0%) and the pre-PCV7 period (children 24.8%; adults 13.3%). In the pre-PCV7 period, macrolide resistance was mainly caused by M-phenotype clones carrying the mefA gene. In the post-PCV7/13 period, ermB (MLSb-phenotype) was the dominant resistance marker. Overall nonsusceptibility rates were 5.5% for clindamycin (intermediate 0.3%, resistant 5.2%), 0.7% for levofloxacin (intermediate 0.4%, resistant 0.3%), 8.5% for

  4. Effect of currently approved carriers and adjuvants on the pre-clinical efficacy of a conjugate vaccine against oxycodone in mice and rats.

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    Marco Pravetoni

    Full Text Available Vaccination against the highly abused prescription opioid oxycodone has shown pre-clinical efficacy for blocking oxycodone effects. The current study further evaluated a candidate vaccine composed of oxycodone derivatized at the C6 position (6OXY conjugated to the native keyhole limpet hemocyanin (nKLH carrier protein. To provide an oxycodone vaccine formulation suitable for human studies, we studied the effect of alternative carriers and adjuvants on the generation of oxycodone-specific serum antibody and B cell responses, and the effect of immunization on oxycodone distribution and oxycodone-induced antinociception in mice and rats. 6OXY conjugated to tetanus toxoid (TT or a GMP grade KLH dimer (dKLH was as effective as 6OXY conjugated to the nKLH decamer in mice and rats, while the 6OXY hapten conjugated to a TT-derived peptide was not effective in preventing oxycodone-induced antinociception in mice. Immunization with 6OXY-TT s.c. absorbed on alum adjuvant provided similar protection to 6OXY-TT administered i.p. with Freund's adjuvant in rats. The toll-like receptor 4 (TLR4 agonist monophosphoryl lipid A (MPLA adjuvant, alone or in combination with alum, offered no advantage over alum alone for generating oxycodone-specific serum antibodies or 6OXY-specific antibody secreting B cells in mice vaccinated with 6OXY-nKLH or 6OXY-TT. The immunogenicity of oxycodone vaccines may be modulated by TLR4 signaling since responses to 6OXY-nKLH in alum were decreased in TLR4-deficient mice. These data suggest that TT, nKLH and dKLH carriers provide consistent 6OXY conjugate vaccine immunogenicity across species, strains and via different routes of administration, while adjuvant formulations may need to be tailored to individual immunogens or patient populations.

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

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    Silvio D Brugger

    Full Text Available BACKGROUND: 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. METHODOLOGY: 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. PRINCIPAL FINDINGS: 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. CONCLUSIONS: 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.

  6. 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

  7. 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 <3.5 EU responded with significantly higher IgG 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.

  8. Results of a Cohort Model Analysis of the Cost-Effectiveness of Routine Immunization With 13-Valent Pneumococcal Conjugate Vaccine of Those Aged >= 65 Years in the Netherlands

    NARCIS (Netherlands)

    Rozenbaum, Mark H.; Hak, Eelko; van der Werf, Tjip S.; Postma, Maarten J.

    2010-01-01

    Background: Community-acquired pneumonia and invasive pneumococcal disease are common among older people (ie, those aged >= 65 years). A new 13-valent pneumococcal conjugate vaccine (PCV-13) is under study in the Netherlands. Objective: The aim of this work was to model the cost-effectiveness of PCV

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

    Science.gov (United States)

    Fortunato, Francesca; Martinelli, Domenico; Cappelli, Maria Giovanna; Cozza, Vanessa; Prato, Rosa

    2015-01-01

    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 children 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.

  10. Safety of the 11-valent pneumococcal vaccine conjugated to non-typeable Haemophilus influenzae-derived protein D in the first 2 years of life and immunogenicity of the co-administered hexavalent diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated polio virus, Haemophilus influenzae type b and control hepatitis A vaccines.

    Science.gov (United States)

    Prymula, Roman; Chlibek, Roman; Splino, Miroslav; Kaliskova, Eva; Kohl, Igor; Lommel, Patricia; Schuerman, Lode

    2008-08-18

    This randomized (1:1), double-blind, multicenter study, included 4,968 healthy infants to receive either the 11-valent pneumococcal protein D (PD)-conjugate study vaccine or the hepatitis A vaccine (HAV) (control) at 3, 4, 5, and 12-15 months of age. The three-dose primary course of both vaccines was co-administered with combined hexavalent DTPa-HBV-IPV/Hib vaccine. The pneumococcal PD-conjugate study vaccine did not impact the immune response of co-administered hexavalent vaccine and the control HAV vaccine induced seropositivity (antibodies >or=15 mIU/mL) in all infants. The incidence of solicited symptoms was higher with the 11-valent pneumococcal PD-conjugate study vaccine, yet similar to that induced by concomitant DTPa-HBV-IPV/Hib vaccine. Overall, the reactogenicity and safety profile of the 11-valent pneumococcal PD-conjugate vaccine when co-administered with the hexavalent DTPa-HBV-IPV/Hib vaccine, as well as the immunogenicity of the co-administered hexavalent vaccine, were consistent with previous reports for the licensed DTPa-HBV-IPV/Hib and pneumococcal conjugate vaccines.

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

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    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.

  12. Depressive symptoms and immune response to meningococcal conjugate vaccine in early adolescence.

    Science.gov (United States)

    O'Connor, Thomas G; Moynihan, Jan A; Wyman, Peter A; Carnahan, Jennifer; Lofthus, Gerry; Quataert, Sally A; Bowman, Melissa; Caserta, Mary T

    2014-11-01

    Research findings in psychoneuroimmunology document reliable, bidirectional linkages among psychological processes, the nervous system, and the immune system. However, available data are based almost entirely on animal and adult human studies; the application to children and adolescents is uncertain. We capitalized on the experimental leverage provided by a routine vaccination to examine the link between mood symptoms and the immune response to a vaccine challenge in early adolescence. One hundred twenty-six 11-year-olds for whom vaccine response data were available were assessed at prevaccination and 4 weeks, 3 months, and 6 months following vaccination; self-report ratings of depression and anxiety as well as measures of psychosocial and somatic risk were assessed prior to vaccine response. Analyses indicated that children's internalizing mood symptoms were associated with elevated and persistently higher antibody responses, with evidence extending to two of the four serogroups. The associations remained after controlling for multiple possible confounders (social class, body mass index, sleep, psychosocial risk, and pubertal status). The observed enhanced vaccine response associated with depressive and anxious symptoms in early adolescence may reflect an important developmental difference in immune system-brain interplay between adults and children, and it underscores the need for further developmental studies of psychoneuroimmunology.

  13. Concomitant administration of Mycobacterium bovis BCG with the meningococcal C conjugate vaccine to neonatal mice enhances antibody response and protective efficacy.

    Science.gov (United States)

    Brynjolfsson, Siggeir F; Bjarnarson, Stefania P; Mori, Elena; Del Giudice, Giuseppe; Jonsdottir, Ingileif

    2011-11-01

    Mycobacterium bovis BCG is administered to human neonates in many countries worldwide. The objective of the study was to assess if BCG could act as an adjuvant for polysaccharide-protein conjugate vaccines in newborns and thereby induce protective immunity against encapsulated bacteria in early infancy when susceptibility is high. We assessed whether BCG could enhance immune responses to a meningococcal C (MenC) conjugate vaccine, MenC-CRM(197), in mice primed as neonates, broaden the antibody response from a dominant IgG1 toward a mixed IgG1 and IgG2a/IgG2b response, and increase protective efficacy, as measured by serum bactericidal activity (SBA). Two-week-old mice were primed subcutaneously (s.c.) with MenC-CRM(197). BCG was administered concomitantly, a day or a week before MenC-CRM(197). An adjuvant effect of BCG was observed only when it was given concomitantly with MenC-CRM(197), with increased IgG response (P = 0.002) and SBA (8-fold) after a second immunization with MenC-CRM(197) without BCG, indicating increased T-cell help. In neonatal mice (1 week old) primed s.c. with MenC-CRM(197) together with BCG, MenC-polysaccharide (PS)-specific IgG was enhanced compared to MenC-CRM(197) alone (P = 0.0015). Sixteen days after the second immunization with MenC-CRM(197), increased IgG (P CRM(197) plus BCG showed affinity maturation and detectable SBA (SBA > 128). Thus, vaccination with a meningococcal conjugate vaccine (and possibly with other conjugates) may benefit from concomitant administration of BCG in the neonatal period to accelerate and enhance production of protective antibodies, compared to the current infant administration of conjugate which follows BCG vaccination at birth.

  14. 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...... subjects were primed with PHiD-CV at either 3 and 5 or 3, 4 and 5 months of age followed in all subjects by a booster dose at 11 to 12 months of age. Serotype-specific pneumococcal responses were measured by 22F-inhibition ELISA and opsonophagocytic assays 1 month following primary and booster vaccinations.......6%, respectively). Opsonophagocytic activity (OPA) could be measured in 74.4% to 100% and 88.9% to 100% of the subjects after the 2-dose or 3-dose priming, respectively, except for serotype 1 (60.8% and 62.9%, respectively). In both groups, robust increases in ELISA antibodies and OPA titers were observed for all...

  15. Polysaccharide Responsiveness Is Not Biased by Prior Pneumococcal-Conjugate Vaccination

    Science.gov (United States)

    Bernth-Jensen, Jens Magnus; Søgaard, Ole Schmeltz

    2013-01-01

    Polysaccharide responsiveness is tested by measuring antibody responses to polysaccharide vaccines to diagnose for humoral immunodeficiency. A common assumption is that this responsiveness is biased by any previous exposure to the polysaccharides in the form of protein-coupled polysaccharide vaccines, such as those used in many childhood vaccination programmes. To examine this assumption, we investigated the effect of protein-coupled polysaccharide vaccination on subsequent polysaccharide responsiveness. HIV-infected adults (n = 47) were vaccinated twice with protein-coupled polysaccharides and six months later with pure polysaccharides. We measured immunoglobulin G responses against three polysaccharides present in only the polysaccharide vaccine (non-memory polysaccharides) and seven recurring polysaccharides (memory polysaccharides). Responsiveness was evaluated according to the consensus guidelines published by the American immunology societies. Impaired responsiveness to non-memory polysaccharides was more frequent than to memory polysaccharides (51% versus 28%, P = 0.015), but the individual polysaccharides did not differ in triggering sufficient responses (74% versus 77%, P = 0.53). Closer analysis revealed important shortcomings of the current evaluation guidelines. The interpreted responseś number and their specificities influenced the likelihood of impaired responsiveness in a complex manor. This influence was propelled by the dichotomous approaches inherent to the American guidelines. We therefore define a novel more robust polysaccharide responsiveness measure, the Z-score, which condenses multiple, uniformly weighted responses into one continuous variable. Using the Z-score, responsiveness to non-memory polysaccharides and memory-polysaccharides were found to correlate (R2 = 0.59, Presponsiveness was not biased by prior protein-coupled polysaccharide vaccination in HIV-infected adults. Studies in additional populations are warranted

  16. Efficacy, but not antibody titer or affinity, of a heroin hapten conjugate vaccine correlates with increasing hapten densities on tetanus toxoid, but not on CRM197 carriers.

    Science.gov (United States)

    Jalah, Rashmi; Torres, Oscar B; Mayorov, Alexander V; Li, Fuying; Antoline, Joshua F G; Jacobson, Arthur E; Rice, Kenner C; Deschamps, Jeffrey R; Beck, Zoltan; Alving, Carl R; Matyas, Gary R

    2015-06-17

    Vaccines against drugs of abuse have induced antibodies in animals that blocked the biological effects of the drug by sequestering the drug in the blood and preventing it from crossing the blood-brain barrier. Drugs of abuse are too small to induce antibodies and, therefore, require conjugation of drug hapten analogs to a carrier protein. The efficacy of these conjugate vaccines depends on several factors including hapten design, coupling strategy, hapten density, carrier protein selection, and vaccine adjuvant. Previously, we have shown that 1 (MorHap), a heroin/morphine hapten, conjugated to tetanus toxoid (TT) and mixed with liposomes containing monophosphoryl lipid A [L(MPLA)] as adjuvant, partially blocked the antinociceptive effects of heroin in mice. Herein, we extended those findings, demonstrating greatly improved vaccine induced antinociceptive effects up to 3% mean maximal potential effect (%MPE). This was obtained by evaluating the effects of vaccine efficacy of hapten 1 vaccine conjugates with varying hapten densities using two different commonly used carrier proteins, TT and cross-reactive material 197 (CRM197). Immunization of mice with these conjugates mixed with L(MPLA) induced very high anti-1 IgG peak levels of 400-1500 μg/mL that bound to both heroin and its metabolites, 6-acetylmorphine and morphine. Except for the lowest hapten density for each carrier, the antibody titers and affinity were independent of hapten density. The TT carrier based vaccines induced long-lived inhibition of heroin-induced antinociception that correlated with increasing hapten density. The best formulation contained TT with the highest hapten density of ≥30 haptens/TT molecule and induced %MPE of approximately 3% after heroin challenge. In contrast, the best formulation using CRM197 was with intermediate 1 densities (10-15 haptens/CRM197 molecule), but the %MPE was approximately 13%. In addition, the chemical synthesis of 1, the optimization of the conjugation

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

    Directory of Open Access Journals (Sweden)

    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.

  18. Antibody persistence and immune memory 15 months after priming with an investigational tetravalent meningococcal tetanus toxoid conjugate vaccine (MenACWY-TT) in toddlers and young children.

    Science.gov (United States)

    Knuf, Markus; Baine, Yaela; Bianco, Veronique; Boutriau, Dominique; Miller, Jacqueline M

    2012-07-01

    The present extension study, conducted in children originally vaccinated at 12-14 mo or 3-5 y of age, assessed antibody persistence and immune memory induced by an investigational tetravalent meningococcal serogroups A, C, W-135 and Y tetanus toxoid conjugate vaccine (MenACWY-TT). In the original study, participants were randomized to receive one dose of MenACWY-TT or licensed age-appropriate meningococcal control vaccines. Fifteen months post-vaccination, all participants underwent serum sampling to evaluate antibody persistence and participants previously vaccinated as toddlers received a polysaccharide challenge to assess immune memory development. Exploratory comparisons showed that (1) All children and ≥ 92.3% of the toddlers maintained serum bactericidal (rSBA) titers ≥ 1:8 at 15 mo post MenACWY-TT vaccination; statistically significantly higher rSBA geometric mean titers (GMTs) were observed compared with control vaccines. (2) At one month after polysaccharide challenge, all toddlers primed with MenACWY-TT or with the monovalent serogroup C conjugate vaccine had rSBA titers ≥ 1:8 and ≥ 1:128 for serogroup C and similar rSBA-GMTs; rSBA-GMTs for serogroups A, W-135 and Y were statistically significantly higher in toddlers primed with MenACWY-TT compared with the control vaccine. Thus, a single dose of MenACWY-TT induced persisting antibodies in toddlers and children and immune memory in toddlers. This study has been registered at www.clinicaltrials.gov NCT00126984.

  19. Is a single infant priming dose of meningococcal serogroup C conjugate vaccine in the United Kingdom sufficient?

    Science.gov (United States)

    Findlow, Helen; Borrow, Ray

    2015-01-01

    In 1999, the UK introduced meningococcal serogroup C conjugate (MCC) vaccination at 2, 3, 4 months of age with a single dose for children 1-18 y In 2006, the schedule was refined to a 2 dose priming schedule with a booster in the second year of life. In 2013, the number of priming doses was reduced to a single priming dose, the booster maintained at 12 months of age and an adolescent booster dose introduced. The paper presents the evidence supporting the reduction in the number of priming doses. A UK study provided evidence for reducing the priming doses of MCC-TT together with the positive correlation of lower quantity of antigen and serum bactericidal antibody (SBA) levels post-primary but a higher magnitude of the booster response. Another UK study, demonstrated one dose of MCC-TT or MCC-CRM197 at 3 months gave comparable responses to 2 doses (SBA titres ≥8) both post-primary vaccination and post-booster Hib/MCC-TT at 12 months. However, the magnitude of the SBA GMT was higher in the MCC-TT primed post-booster. A single priming dose of MCC-TT (at 4 or 6 months) compared to 2 doses (2 and 4 months) gave higher SBA titres in all groups, post-primary and post-booster at 12-13 months, with the highest SBA responses observed in the 4 month single dose group. A study in Malta, comparing one dose of MCC-TT or MCC-CRM197 at (3 months) versus 2 doses of MCC-CRM197 (3 and 4 months), showed a high proportion (>84.72%) of subjects achieving SBA titres ≥8 following a single dose. These studies show that a single-dose priming MCC vaccination in infancy is sufficient.

  20. Stimulation of immune systems by conjugated polymers and their potential as an alternative vaccine adjuvant

    Science.gov (United States)

    Gong, Hua; Xiang, Jian; Xu, Ligeng; Song, Xuejiao; Dong, Ziliang; Peng, Rui; Liu, Zhuang

    2015-11-01

    Recently, conjugated polymers have been widely explored in the field of nanomedicine. Careful evaluations of their biological effects are thus urgently needed. Hereby, we systematically evaluated the biological effects of different types of conjugated polymers on macrophages and dendritic cells (DCs), which play critical roles in the innate and adaptive immune systems, respectively. While naked poly-(3,4-ethylenedioxythiophene):poly(4-styrenesulfonate) (PEDOT:PSS) exhibits a high level of cytotoxicity, polyethylene glycol (PEG) modified PEDOT:PSS (PEDOT:PSS-PEG) shows greatly reduced toxicity to various types of cells. To our surprise, PEGylation of PEDOT:PSS could obviously enhance the cellular uptake of these nanoparticles, leading to subsequent immune stimulations of both macrophages and DCs. In contrast, another type of conjugated polymer, polypyrrole (PPy), is found to be an inert material with neither significant cytotoxicity nor noticeable immune-stimulation activity. Interestingly, utilizing ovalbumin (OVA) as a model antigen, it is further uncovered in our ex vivo experiment that PEDOT:PSS-PEG may serve as an adjuvant to greatly enhance the immunogenicity of OVA upon simple mixing. Our study on the one hand suggests the promise of developing novel nano-adjuvants based on conjugated polymers, and on the other hand highlights the importance of careful evaluations of the impacts of any new nanomaterials developed for nanomedicine on the immune systems.Recently, conjugated polymers have been widely explored in the field of nanomedicine. Careful evaluations of their biological effects are thus urgently needed. Hereby, we systematically evaluated the biological effects of different types of conjugated polymers on macrophages and dendritic cells (DCs), which play critical roles in the innate and adaptive immune systems, respectively. While naked poly-(3,4-ethylenedioxythiophene):poly(4-styrenesulfonate) (PEDOT:PSS) exhibits a high level of cytotoxicity

  1. Effect of combined pneumococcal conjugate and polysaccharide vaccination on recurrent otitis media with effusion.

    NARCIS (Netherlands)

    Heerbeek, N. van; Straetemans, M.; Wiertsema, S.P.; Ingels, K.J.A.O.; Rijkers, G.T.; Schilder, A.G.M.; Sanders, E.A.M.; Zielhuis, G.A.

    2006-01-01

    BACKGROUND: Otitis media with effusion (OME) is very common during childhood. Because Streptococcus pneumoniae is one of the most common bacterial pathogens involved in OME, pneumococcal vaccines may have a role in the prevention of recurrent OME. OBJECTIVE: We sought to assess the effect of

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

    Directory of Open Access Journals (Sweden)

    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.

  3. Nanoparticle and polysaccharide conjugate: a potential candidate vaccine to improve immunological stimuli.

    Science.gov (United States)

    Devi, K Sanjana P; Sahoo, Banalata; Behera, Birendra; Maiti, Tapas K

    2015-01-01

    Active polysaccharides isolated from various fungal sources have been implicated to stimulate immune response against various pathogens as well as self anomalies such as cancer. Therefore, the nuanced approach presented in our work was to blend polysaccharides derived from Pleurotus ostreatus with biocompatible ferrite nanoparticles and thereafter investigate the enhanced immune functionality of the polysaccharide-nanoparticle composite. A Schiff base reductive amination reaction occurred between the aldehyde group of the polysaccharide and the amine group of the nanoparticles in the presence of a strong reducing agent such as sodium cyanoborohydride to form a stable amide bond between the two conjugating molecules. The multifaceted conjugate was characterized by physiochemical techniques such as electron microscopy, FTIR, VSM and DLS measurements. This particulate form of the polysaccharide showed a marked escalation in the production of free radicals such as reactive oxygen and nitrogen species in murine macrophages as compared to the soluble form. Animal based experiments demonstrated a reduction in tumor volume and augmentation in the proliferation of splenocytes in particulate or conjugated polysaccharide treated mice. Furthermore, molecular signaling studies showed a high upregulation in p-p38 and p-MEK molecules in particulate polysaccharide treated RAW264.7 cells suggesting a cellular downstream mechanistic regulation behind the immunostimulative response.

  4. Impact of meningococcal C conjugate vaccination campaign in Emilia-Romagna, Italy.

    Science.gov (United States)

    Pascucci, Maria Grazia; Di Gregori, Valentina; Frasca, Gabriella; Rucci, Paola; Finarelli, Alba Carola; Moschella, Laura; Borrini, Bianca Maria; Cavrini, Francesca; Liguori, Giovanna; Sambri, Vittorio; Bonanni, Paolo; Fantini, Maria Pia

    2014-01-01

    The incidence of reported meningococcal disease in Italy is among the lowest in Europe. The trend of the disease was increasing up to 2005 and then declined after the gradual introduction of a universal Men C vaccination program in 17/21 Italian regions. Since 2006, in Emilia-Romagna region vaccination against Neisseria meningitidis serogroup C was actively offered free of charge in a single dose to the age groups 12-15 months and 14-15 years, in addition to people with defined epidemiological risk. Our aim was to measure the impact of vaccination on the incidence of meningococcal disease caused by different serogroups among the population of Emilia Romagna Region, Northern Italy (approximately 4.5 million inhabitants) subdivided by age. Using surveillance data, we computed the incidence rates of Neisseria meninigitidis related invasive disease per 100.000 inhabitants for the years 2000 to 2012. In addition, the percentage change in incidence and the mortality rates were calculated. Results indicate a 70.1% decrease in the incidence of meningococcus C-related invasive disease after the introduction of MenC universal vaccination. No case of serogroup C related infection was observed since 2006 in children aged 1-4 years. These findings suggest that the single-dose vaccination strategy against serogroup C N.meningitidis targeted to the age groups 12-15 months and 14-15 years was effective in the Emilia-Romagna population. However, the occurrence of two cases of meningiditis in a 5-month child and in a 9-years child suggests caution and careful consideration in surveillance for the next years.

  5. Pilot study of a heptavalent vaccine-keyhole limpet hemocyanin conjugate plus QS21 in patients with epithelial ovarian, fallopian tube, or peritoneal cancer

    DEFF Research Database (Denmark)

    Sabbatini, Paul J; Ragupathi, Govind; Hood, Chandra

    2007-01-01

    PURPOSE: To characterize the safety and immunogenicity of a heptavalent antigen-keyhole limpet hemocyanin (KLH) plus QS21 vaccine construct in patients with epithelial ovarian, fallopian tube, or peritoneal cancer in second or greater complete clinical remission. EXPERIMENTAL DESIGN: Eleven......). RESULTS: Eleven patients were included in the safety analysis; 9 of 11 patients remained on study for at least 2 weeks past fourth vaccination and were included in the immunologic analysis (two withdrew, disease progression). The vaccine was well tolerated. Self-limited and mild fatigue (maximum grade 2...... in seven of nine patients, with some increase seen in all patients. CONCLUSIONS: This heptavalent-KLH conjugate plus QS21 vaccine safely induced antibody responses against five of seven antigens. Investigation in an adequately powered efficacy trial is warranted....

  6. Immunogenicity of meningococcal quadrivalent (serogroup A, C, W135 and Y) tetanus toxoid conjugate vaccine: systematic review and meta-analysis.

    Science.gov (United States)

    Pellegrino, Paolo; Perrone, Valentina; Radice, Sonia; Capuano, Annalisa; Clementi, Emilio

    2015-02-01

    Meningococcal meningitis represents one of the leading cause of bacterial meningitis in developed countries. Among the thirteen described serogroups, only five are usually responsible of invasive infections making immunisation against multiple serogroups the best strategy to protect individuals from this disease. Herein we carried out a systematic review and meta-analysis, in accordance with the PRISMA statement, of the recently EU-licensed meningococcal ACWY-tetanus toxoid conjugate vaccine (MenACWY-TT). We included 15 randomised clinical trials, comparing MenACWY-TT and Men-PS (ten studies), MenACWY-TT and MenC-CRM197 (four studies) and MenACWY-TT and MenACWY-DT (one study). All studies included in the meta-analysis showed high immunogenicity for MenACWY-TT vaccines in all tested serogroups. Our results suggest that the MenACWY-TT vaccine is as immunogenic as the other commercial available meningococcal vaccines.

  7. Opposite effects of actively and passively acquired immunity to the carrier on responses of human infants to a Haemophilus influenzae type b conjugate vaccine

    DEFF Research Database (Denmark)

    Barington, T; Gyhrs, A; Kristensen, Kim

    1994-01-01

    Vaccination of infants with Haemophilus influenzae type b (Hib) capsular polysaccharide (HibCP) coupled to carrier proteins has proven protective against invasive Hib diseases in several trials. However, insufficient immunogenicity has been noted in certain populations. Therefore, studies analyzing...... factors influencing the antibody response to conjugate vaccines are needed. In this study, the response to HibCP coupled to tetanus toxoid (TT) was examined in relation to (i) priming with or coadministration of the carrier protein and (ii) the levels of passively acquired maternal TT antibodies. One...... hundred forty-four infants were vaccinated with HibCP-TT at 5 and 6 months. They were randomized into three groups that received TT as part of a diphtheria-tetanus-polio vaccine at either 6 and 7 months (group A), 5 and 6 months (group B), or 4 and 5 months (group C). Maternally acquired TT antibodies...

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

    Directory of Open Access Journals (Sweden)

    Pierre van Damme

    Full Text Available BACKGROUND: 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. METHODOLOGY: 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. PRINCIPAL FINDINGS: 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. CONCLUSIONS: Vi-CRM₁₉₇ did not elicit safety concerns, was highly immunogenic and is therefore suitable for further clinical testing in endemic populations of South Asia. TRIAL REGISTRATION: ClinicalTrials.gov NCT01123941 NCT01193907.

  9. Human /avian influenza conjugated vaccines for human use%人用流感禽流感联合疫苗的研究

    Institute of Scientific and Technical Information of China (English)

    朱函坪; 陈学奎; 姚苹苹; 徐芳; 谢荣辉; 杨章女; 李岩金; 朱智勇

    2011-01-01

    目的 了解人流感疫苗和H5N1禽流感疫苗联合后的安全性和疫苗之间产生抗体的相互干扰现象.方法 制成禽流感单价疫苗、人流感3价疫苗和流感禽流感联合4价疫苗,免疫家兔,测定中和抗体和血凝抑制抗体,并接种小鼠和豚鼠,观察毒性反应和过敏反应.结果 人流感疫苗和禽流感疫苗的联合,基本上没有发生疫苗对各自抗体产生的干扰;接种动物无毒性反应.结论 2种疫苗的联合是完全可能的.%In this study, the safety of the influenza vaccine conjugated with H5N1 avian influenza vaccine were investigated, and the cross-reaction between the two vaccines were tested.The monovalent-, tervalent- and quadrivalent- influenza vaccines and avian influenza were prepared, rabbits were immunized subsequently, and neutralizing antibodies and haemagglutination inhibition antibodies were further measured.Additionally, these vaccines were used to inoculate mouse and guinea pig, and monitored the toxicity and allergic effects.Our results demonstrated that no cross-reaction was observed using influenza vaccine conjugating with H5N1 avian influenza vaccine, nor toxicity occurred, indicating the potential application of these two conjgated vaccines.

  10. Meningococcal Disease in US Military Personnel Before and after Adoption of Conjugate Vaccine

    Science.gov (United States)

    2015-02-01

    Serogroup B accounted for 5 of the 8 cases during 2012–September 2014), and prevention of disease caused by this serotype remains a challenge...Acknowledgment We thank CDC’s Meningitis and Vaccine Preventable Diseases Branch for providing the US disease data. The Naval Health Research Center...A226V mutation of the E1 protein (2), the transmission of which is reported to be facilitated by Aedes albopictus mosquitoes (3). The ECSA

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

    Directory of Open Access Journals (Sweden)

    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.

  12. Working Group on quality, safety and efficacy of typhoid Vi capsular polysaccharide conjugate, vaccines, Jeju, Republic of Korea, 5-7 September 2012.

    Science.gov (United States)

    Jones, Chris; Lee, Chung Keel; Ahn, Chiyoung; Shin, Jinho; Knezevic, Ivana

    2013-09-23

    Typhoid fever is a gastrointestinal disease transmitted through the ingestion of contaminated water or food. The bacterium, Salmonella enterica subspecies enterica serovar Typhi is an important cause of illness and death in many poor countries where access to safe water and basic sanitation is limited. Humans are the only natural host and reservoir of S. Typhi. Typhoid fever causes around 21 million cases and at least 200,000 deaths per year. Currently, several groups are developing typhoid conjugate vaccines that are expected to be safe and effective in infancy or early childhood. The World Health Organization convened a meeting, in collaboration with the Korea Food and Drug Administration, with experts group in September 2012 to develop guidelines for regulatory evaluation of the quality, safety and efficacy of typhoid conjugate vaccines. This report summarizes collective views on scientific and technical issues that need to be considered in the guidelines.

  13. 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.

  14. 由结合疫苗产品历史沿革带来的思考%Some reflections from the history of conjugate vaccine development

    Institute of Scientific and Technical Information of China (English)

    杜琳(综述); 蒋仁生(审校)

    2013-01-01

    由于优异安全性和有效性数据,结合疫苗已成为细菌性疫苗研制的一个方向,但因不同团体独立研发,产生了不同的结合技术,也带来了一些困惑。通过对几个具有代表性的结合疫苗研发团队的研究历程的回顾,探讨了结合方法、载体蛋白质、剂型等热点话题,以期对结合疫苗的研制有所帮助。%Due to the excellent safety and efficacy data , conjugate vaccine has become a direction for bacterial vaccine de-velopment ., but different conjugate technologies from different independent research groups also brought some confusion . After reviewing the research history of some representative team , conjugate methods , carrier protein , vaccine formulation and other hot topics were discussed .

  15. Preparation and testing of a Vi conjugate vaccine using pneumococcal surface protein A (PspA) from Streptococcus pneumoniae as the carrier protein.

    Science.gov (United States)

    Kothari, Neha; Genschmer, Kristopher R; Kothari, Sudeep; Kim, Jeong Ah; Briles, David E; Rhee, Dong Kwon; Carbis, Rodney

    2014-09-29

    In the current study pneumococcal surface protein A (PspA) was conjugated to Vi capsular polysaccharide from Salmonella Typhi to make available a vaccine against typhoid fever that has the potential to also provide broad protection from Streptococcus pneumoniae. High yielding production processes were developed for the purification of PspAs from families 1 and 2. The purified PspAs were conjugated to Vi with high recovery of both Vi and PspA. The processes developed especially for PspA family 2 could readily be adapted for large scale production under cGMP conditions. Previously we have shown that conjugation of diphtheria toxoid (DT) to Vi polysaccharide improves the immune response to Vi but can also enhance the response to DT. In this study it was shown that conjugation of PspA to Vi enhanced the anti-PspA response and that PspA was a suitable carrier protein as demonstrated by the characteristics of a T-cell dependent response to the Vi. We propose that a bivalent vaccine consisting of PspA from families 1 and 2 bound to Vi polysaccharide would protect against typhoid fever and has the potential to also protect against pneumococcal disease and should be considered for use in developing countries.

  16. Microparticulate β-glucan vaccine conjugates phagocytized by dendritic cells activate both naïve CD4 and CD8 T cells in vitro.

    Science.gov (United States)

    Berner, Vanessa K; duPre, Sally A; Redelman, Doug; Hunter, Kenneth W

    2015-01-01

    Microparticulate β-glucan (MG) conjugated to vaccine antigen has been shown to serve as an effective adjuvant in vivo. To further study antigen presentation by MG:vaccine conjugates, bone marrow-derived dendritic cells (BMDC) were treated with MG conjugated to ovalbumin (OVA), then interacted with splenocytes from DO11.10 transgenic mice expressing an OVA peptide-specific T cell receptor. BMDC treated with MG:OVA induced significantly higher numbers of activated (CD25+CD69+) OVA-specific CD4+ T cells than BMDC treated with OVA alone. BMDC treated with MG:OVA upregulated CD86 and CD40 expression as well as MG alone, indicating that conjugation of OVA does not alter the immunostimulatory capacity of MG. Activation of CD8+ OVA-specific OT-1 cells showed that MG:OVA is also capable of enhancing cross-presentation by BMDC to CD8+ cytotoxic T cells. These results show that MG acts as an adjuvant to enhance antigen presentation by dendritic cells to naïve, antigen-specific CD4 and CD8 T cells.

  17. 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

    2016-04-01

    Vi polysaccharide typhoid vaccines cannot be used in children vaccine prepared by binding Vi to tetanus toxoids (Vi-TT) induces protective levels even in children 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.

  18. 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.

  19. Impact on respiratory tract infections of heptavalent pneumococcal conjugate vaccine administered at 3, 5 and 11 months of age

    Directory of Open Access Journals (Sweden)

    Cesati Laura

    2007-02-01

    Full Text Available Abstract Background Medical and public health importance of pneumococcal infections justifies the implementation of measures capable of reducing their incidence and severity, and explains why the recently marketed heptavalent pneumococcal conjugate vaccine (PCV-7 has been widely studied by pediatricians. This study was designed to evaluate the impact of PCV-7 administered at 3, 5 and 11 months of age on respiratory tract infections in very young children. Methods A total of 1,571 healthy infants (910 males aged 75–105 days (median 82 days were enrolled in this prospective cohort trial to receive a hexavalent vaccine (DTaP/IPV/HBV/Hib and PCV-7 (n = 819 or the hexavalent vaccine alone (n = 752 at 3, 5 and 11 months of age. Morbidity was recorded for the 24 months following the second dose by monthly telephone interviews conducted by investigators blinded to the study treatment assignment using standardised questionnaires. During these interviews, the caregivers and the children's pediatricians were questioned about illnesses and the use of antibiotics since the previous telephone call. All of the data were analysed using SAS Windows v.12. Results Among the 1,555 subjects (98.9% who completed the study, analysis of the data by the periods of follow-up demonstrated that radiologically confirmed community-acquired pneumonia (CAP was significantly less frequent in the PCV-7 group during the follow-up as a whole and during the last period of follow-up. Moreover, there were statistically significant between-group differences in the incidence of acute otitis media (AOM in each half-year period of follow-up except the first, with significantly lower number of episodes in children receiving PCV-7 than in controls. Furthermore, the antibiotic prescription data showed that the probability of receiving an antibiotic course was significantly lower in the PCV-7 group than in the control group. Conclusion Our findings show the effectiveness of the simplified

  20. Population structure of invasive Streptococcus pneumoniae isolates among Alaskan children in the conjugate vaccine era, 2001 to 2013.

    Science.gov (United States)

    Miernyk, Karen M; Bulkow, Lisa R; Case, Samantha L; Zulz, Tammy; Bruce, Michael G; Harker-Jones, Marcella; Hurlburt, Debby A; Hennessy, Thomas W; Rudolph, Karen M

    2016-10-01

    Here we describe the relationships between serotypes, genotypes, and antimicrobial susceptibility among isolates causing invasive pneumococcal disease in Alaskan children during the pneumococcal conjugate vaccine (PCV) era. From 2001 to 2013 we received 271 isolates representing 33 serotypes. The most common serotypes were 19A (29.5%, n= 80), 7F (12.5%, n= 34), 15B/C (6.3%, n= 17), and 22F (4.8%, n= 13). Multilocus sequence typing identified 11 clonal complexes (CC) and 45 singletons. Five CCs accounted for 52% (141/271) of the total: CC199 (21% [n= 57], serotypes 19A, 15B/C), CC191 (12.2% [n= 33], serotype 7F), CC172 (10.3% [n= 28], serotypes 19A, 23A, 23B), CC433 (4.4% [n= 12], serotype 22F), and CC100 (4.4% [n= 12], serotype 33F). The proportion of isolates nonsusceptible to erythromycin and tetracycline increased after 13-valent PCV use (14% [n= 30] versus 29% [n= 14]; P= 0.010) and (4% [n= 9] versus 22% [n= 11]; P< 0.001), respectively. The genetic diversity also increased after 13-valent PCV use (Simpson's diversity index =0.95 versus 0.91; P= 0.022).

  1. Streptococcus pneumoniae serotype distribution in Vojvodina before the introduction of pneumococcal conjugate vaccines into the National Immunization Program: Erratum

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    Editorial

    2016-01-01

    Full Text Available In the article that appeared on pages 521-526 of the September-October 2016 issue of the Serbian Archives of Medicine (Srpski arhiv za celokupno lekarstvo, an incorrect figure - an MRI scan unrelated to the article in question - was published on page 523 instead of Graph 1. The publisher regrets this error. Below is the correct graph, as it should have appeared in the original publication of the article. REFERENCE Petrović V, Šeguljev Z, Ristić M, Djekić-Malbaša J, Radosavljević B, Medić D, Mihajlović-Ukropina M, Hadnadjev M, Gajić I, Opavski N. Streptococcus pneumoniae serotype distribution in Vojvodina before the introduction of pneumococcal conjugate vaccines into the National Immunization Program. Srp Arh Celok Lek. 2016 Sep-Oct; 144(9-10:521-526. (doi: 10.2298/SARH1610521P Link to the corrected article 10.2298/SARH1610521P

  2. Acute otorrhea in children with tympanostomy tubes: prevalence of bacteria and viruses in the post-pneumococcal conjugate vaccine era.

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    van Dongen, Thijs M A; Venekamp, Roderick P; Wensing, Annemarie M J; Bogaert, Debby; Sanders, Elisabeth A M; Schilder, Anne G M

    2015-04-01

    Acute tympanostomy-tube otorrhea is a common sequela in children with tympanostomy tubes. Acute tympanostomy-tube otorrhea is generally a symptom of an acute middle ear infection, whereby middle ear fluid drains through the tube. The widespread use of pneumococcal conjugate vaccination (PCV) has changed the bacterial prevalence in the upper respiratory tract of children, but its impact on bacterial and viral pathogens causing acute tympanostomy-tube otorrhea is yet unknown. This study was performed in the post-PCV7 era parallel to a randomized clinical trial of the clinical and cost-effectiveness of ototopical and systemic antibiotics and initial observation in 230 children aged 1 to 10 years with untreated, uncomplicated acute tympanostomy-tube otorrhea. Otorrhea and nasopharyngeal samples were collected at baseline (before treatment) and at 2 weeks (after treatment). Conventional bacterial culture was performed followed by antimicrobial-resistance assessment. Viruses were identified by polymerase chain reaction. At baseline, Haemophilus influenzae (41%), Staphylococcus aureus (40%) and Pseudomonas aeruginosa (18%) were the most prevalent bacteria in otorrhea, followed by Streptococcus pneumoniae (7%) and Moraxella catarrhalis (4%). Most pneumococci were non-PCV7 serotypes. Viruses were detected in 45 otorrhea samples at baseline (21%). Most infections were polymicrobial and overall antimicrobial resistance was low. H. influenzae, S. aureus and P. aeruginosa are the most common microorganisms in children with untreated uncomplicated acute tympanostomy-tube otorrhea. Prevalence of S. pneumoniae has decreased since the introduction of PCV and most pneumococci are nonvaccine serotypes.

  3. 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

  4. The incidence of pediatric invasive Haemophilus influenzae and pneumococcal disease in Chiba prefecture, Japan before and after the introduction of conjugate vaccines.

    Science.gov (United States)

    Ishiwada, Naruhiko; Hishiki, Haruka; Nagasawa, Koo; Naito, Sachiko; Sato, Yasunori; Chang, Bin; Sasaki, Yuko; Kimura, Kouji; Ohnishi, Makoto; Shibayama, Keigo

    2014-09-22

    The Haemophilus influenzae type b (Hib) vaccine and the heptavalent pneumococcal conjugate vaccine (PCV7) were introduced in Japan in 2008 and 2010, respectively. In 2011, immunization with these two vaccines was encouraged throughout Japan through a governmental program. Children treated in Chiba prefecture for culture-proven invasive H. influenzae disease (IHiD) and invasive Streptococcus pneumoniae disease (IPD) were identified in a prefectural surveillance study from 2008 to 2013. The incidence rate ratio (IRR) and its confidence interval (CI) were calculated to compare the 3 years before and after governmental financial support for vaccination. The average number of IHiD and IPD cases among children <5 years of age in 2011-2013 decreased 84% (IRR: 0.16, 95% CI: 0.09-0.26, p<0.0001) and 51% (IRR: 0.49, 95% CI: 0.37-0.63, p<0.0001) compared with those occurring in 2008-2010. The most common non-PCV7 serotype encountered in 2011 and 2013 was 19A. After governmental subsidization of Hib and PCV7 vaccination, IHiD and IPD decreased in Chiba prefecture, Japan. Continuous surveillance is necessary to determine the effectiveness of these two vaccines and for detection of emerging invasive serotypes.

  5. Molecular Characterization of Invasive Meningococcal Isolates from Countries in the African Meningitis Belt before Introduction of a Serogroup A Conjugate Vaccine

    Science.gov (United States)

    Caugant, Dominique A.; Kristiansen, Paul A.; Wang, Xin; Mayer, Leonard W.; Taha, Muhamed-Kheir; Ouédraogo, Rasmata; Kandolo, Denis; Bougoudogo, Flabou; Sow, Samba; Bonte, Laurence

    2012-01-01

    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. PMID:23029368

  6. Engineering, conjugation, and immunogenicity assessment of Escherichia coli O121 O antigen for its potential use as a typhoid vaccine component.

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    Wetter, Michael; Kowarik, Michael; Steffen, Michael; Carranza, Paula; Corradin, Giampietro; Wacker, Michael

    2013-07-01

    State-of-the-art production technologies for conjugate vaccines are complex, multi-step processes. An alternative approach to produce glycoconjugates is based on the bacterial N-linked protein glycosylation system first described in Campylobacter jejuni. The C. jejuni N-glycosylation system has been successfully transferred into Escherichia coli, enabling in vivo production of customized recombinant glycoproteins. However, some antigenic bacterial cell surface polysaccharides, like the Vi antigen of Salmonella enterica serovar Typhi, have not been reported to be accessible to the bacterial oligosaccharyltransferase PglB, hence hamper development of novel conjugate vaccines against typhoid fever. In this report, Vi-like polysaccharide structures that can be transferred by PglB were evaluated as typhoid vaccine components. A polysaccharide fulfilling these requirements was found in Escherichia coli serovar O121. Inactivation of the E. coli O121 O antigen cluster encoded gene wbqG resulted in expression of O polysaccharides reactive with antibodies raised against the Vi antigen. The structure of the recombinantly expressed mutant O polysaccharide was elucidated using a novel HPLC and mass spectrometry based method for purified undecaprenyl pyrophosphate (Und-PP) linked glycans, and the presence of epitopes also found in the Vi antigen was confirmed. The mutant O antigen structure was transferred to acceptor proteins using the bacterial N-glycosylation system, and immunogenicity of the resulting conjugates was evaluated in mice. The conjugate-induced antibodies reacted in an enzyme-linked immunosorbent assay with E. coli O121 LPS. One animal developed a significant rise in serum immunoglobulin anti-Vi titer upon immunization.

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

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    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.

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

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    Deron C Burton

    Full Text Available 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.

  9. Vaccinations

    Science.gov (United States)

    ... vaccinated? For many years, a set of annual vaccinations was considered normal and necessary for dogs and ... to protect for a full year. Consequently, one vaccination schedule will not work well for all pets. ...

  10. 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.

  11. Immune interference on conjugate vaccines by carrier proteins or co-administrated vaccines%载体蛋白及多种疫苗同时接种对结合疫苗的免疫干扰

    Institute of Scientific and Technical Information of China (English)

    朱为

    2012-01-01

    多种多糖-蛋白结合疫苗被开发成功,用于预防b型流感嗜血杆菌、脑膜炎球菌和肺炎链球菌感染,为婴幼儿健康提供了保障.常用的载体蛋白是破伤风类毒素、白喉类毒素和白喉类毒素突变体CRM197.在临床研究中观察到,相同载体或不同载体结合疫苗同时接种,或者与DTP/HBV/IPV等疫苗同时接种时,会干扰对某些抗原的免疫应答,其中可能有多种机制在起作用.随着更多的结合疫苗有望进入婴幼儿期基础免疫程序和无细胞百日咳疫苗(aP)逐渐代替全细胞百日咳疫苗(wP),如何选择合适的或者新的载体蛋白和佐剂、谨慎设计临床研究方案和接种程序等问题日益受到关注.%Polysaccharide-protein conjugate vaccines are developed successfully to prevent Haemophilus influenzae type b,Neisseria meningitidis and Streptococus pnuemoniae infections,especially for infants.The most commonly used carrier proteins are tetanus toxoid,diphtheria toxoid,and diphtheria toxin variant CRM197.In clinical trials,immune interference has been observed when conjugate vaccines with the same or different carrier proteins were co-administrated,or the conjugate vaccines were immunized concurrently with DTP/HBV/IPV.Several mechanisms may work together.As more conjugate vaccines are expected to be included into the childhood primary immunization schedule,and whole cell pertussis vaccine (wP) is replaced by acellular pertussis vaccine (aP) gradually,the problemns,including how to choose suitable carrier proteins and adjuvants,carefully designing the clinical trial and immunization schedule,attract more people's attention.

  12. Bacterial Density, Serotype Distribution and Antibiotic Resistance of Pneumococcal Strains from the Nasopharynx of Peruvian Children Before and After Pneumococcal Conjugate Vaccine 7

    Science.gov (United States)

    Hanke, Christiane R.; Grijalva, Carlos G.; Chochua, Sopio; Pletz, Mathias W.; Hornberg, Claudia; Edwards, Kathryn M.; Griffin, Marie R.; Verastegui, Hector; Gil, Ana I.; Lanata, Claudio F.; Klugman, Keith P.; Vidal, Jorge E.

    2016-01-01

    Background Pneumococcal conjugate vaccines (PCV) have decreased nasopharyngeal carriage of vaccine-types but little data exists from rural areas. We investigated bacterial density, serotype distribution and antibiotic resistance of pneumococcal strains within the nasopharynx of young children in the Peruvian Andes, two years after PCV7 was introduced. Methods Pneumococcal strains were isolated from a subset of 125 children from our Peruvian cohort, who entered the study in 2009 and had pneumococcus detected in the nasopharynx in both 2009 and during follow-up in 2011. Strains were quellung-serotyped and tested for susceptibility to antibiotics. Bacterial density was determined by qPCR. Results The prevalence of PCV7 strains decreased from 48% in 2009 to 28.8% in 2011, whereas non-PCV7 types increased from 52% to 71.2% (p=0.002). There was a 3.5-fold increase in carriage of serotype 6C in 2011 (p=0.026). Vaccination with PCV7 did not affect pneumococcal density in children colonized by a PCV7 type but did increased density in those colonized with a non-PCV7 type. Antibiotic resistance did not change after vaccine introduction; strains were non-susceptible to tetracycline (97.2%), trimethoprim-sulfamethoxazole (56.4%), penicillin (34%), erythromycin (22.4%), chloramphenicol (18.8%) and clindamycin (12.4%). Conclusions Serotype replacement was observed post-PCV7 vaccination with a concomitant, not previously recognized, increased nasopharyngeal density. PMID:26974749

  13. 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.

  14. 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.

  15. 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

  16. Nasopharyngeal carriage and transmission of Streptococcus pneumoniae in American Indian households after a decade of pneumococcal conjugate vaccine use.

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    Jonathan F Mosser

    Full Text Available BACKGROUND: Young children played a major role in pneumococcal nasopharyngeal carriage, acquisition, and transmission in the era before pneumococcal conjugate vaccine (PCV use. Few studies document pneumococcal household dynamics in the routine-PCV7 era. METHODS: We investigated age-specific acquisition, household introduction, carriage clearance, and intra-household transmission in a prospective, longitudinal, observational cohort study of pneumococcal nasopharyngeal carriage in 300 American Indian households comprising 1,072 participants between March 2006 and March 2008. RESULTS: Pneumococcal acquisition rates were 2-6 times higher in children than adults. More household introductions of new pneumococcal strains were attributable to children <9 years than adults ≥17 years (p<0.001, and older children (2-8 years than younger children (<2 years (p<0.008. Compared to children <2 years, carriage clearance was more rapid in older children (2-4 years, HRclearance 1.53 [95% CI: 1.22, 1.91]; 5-8 years, HRclearance 1.71 [1.36, 2.15] and adults (HRclearance 1.75 [1.16, 2.64]. Exposure to serotype-specific carriage in older children (2-8 years most consistently increased the odds of subsequently acquiring that serotype for other household members. CONCLUSIONS: In this community with a high burden of pneumococcal colonization and disease and routine PCV7 use, children (particularly older children 2-8 years drive intra-household pneumococcal transmission: first, by acquiring, introducing, and harboring pneumococcus within the household, and then by transmitting acquired serotypes more efficiently than household members of other ages.

  17. Effectiveness of the 10-Valent Pneumococcal Conjugate Vaccine (PCV-10) in Children in Chile: A Nested Case-Control Study Using Nationwide Pneumonia Morbidity and Mortality Surveillance Data

    Science.gov (United States)

    Toscano, Cristiana M.; Alencar, Gizelton P.; Alvarez, Andrés; Valenzuela, Maria T.; Andrus, Jon; del Aguila, Roberto; Hormazábal, Juan C.; Araya, Pamela; Pidal, Paola; Matus, Cuauhtemoc R.; de Oliveira, Lucia H.

    2016-01-01

    Background The ten-valent pneumococcal conjugate vaccine (PCV10) was introduced into the Chilean National Immunization Program (NIP) in January 2011 with a 3+1 schedule (2, 4, 6 and 12 months) without catch-up vaccination. We evaluated the effectiveness of PCV10 on pneumonia morbidity and mortality among infants during the first two years after vaccine introduction. Methods This is a population-based nested case-control study using four merged nationwide case-based electronic health data registries: live birth, vaccination, hospitalization and mortality. Children born in 2010 and 2011 were followed from two moths of age for a period of two years. Using four different case definitions of pneumonia hospitalization and/or mortality (all-cause and pneumonia related deaths), all cases and four randomly selected matched controls per case were selected. Controls were matched to cases on analysis time. Vaccination status was then assessed. Vaccine effectiveness (VE) was estimated using conditional logistic regression. Results There were a total of 497,996 children in the 2010 and 2011 Chilean live-birth cohorts. PCV10 VE was 11.2% (95%CI 8.5–13.6) when all pneumonia hospitalizations and deaths were used to define cases. VE increased to 20.7 (95%CI 17.3–23.8) when ICD10 codes used to denote viral pneumonia were excluded from the case definition. VE estimates on pneumonia deaths and all-cause deaths were 71.5 (95%CI 9.0–91.8) and 34.8 (95% CI 23.7–44.4), respectively. Conclusion PCV10 vaccination substantially reduced the number of hospitalizations due to pneumonia and deaths due to pneumonia and to all-causes over this study period. Our findings also reinforce the importance of having quality health information systems for measuring VE. PMID:27058873

  18. Effectiveness of the 10-Valent Pneumococcal Conjugate Vaccine (PCV-10) in Children in Chile: A Nested Case-Control Study Using Nationwide Pneumonia Morbidity and Mortality Surveillance Data.

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    Diaz, Janepsy; Terrazas, Solana; Bierrenbach, Ana L; Toscano, Cristiana M; Alencar, Gizelton P; Alvarez, Andrés; Valenzuela, Maria T; Andrus, Jon; del Aguila, Roberto; Hormazábal, Juan C; Araya, Pamela; Pidal, Paola; Matus, Cuauhtemoc R; de Oliveira, Lucia H

    2016-01-01

    The ten-valent pneumococcal conjugate vaccine (PCV10) was introduced into the Chilean National Immunization Program (NIP) in January 2011 with a 3+1 schedule (2, 4, 6 and 12 months) without catch-up vaccination. We evaluated the effectiveness of PCV10 on pneumonia morbidity and mortality among infants during the first two years after vaccine introduction. This is a population-based nested case-control study using four merged nationwide case-based electronic health data registries: live birth, vaccination, hospitalization and mortality. Children born in 2010 and 2011 were followed from two moths of age for a period of two years. Using four different case definitions of pneumonia hospitalization and/or mortality (all-cause and pneumonia related deaths), all cases and four randomly selected matched controls per case were selected. Controls were matched to cases on analysis time. Vaccination status was then assessed. Vaccine effectiveness (VE) was estimated using conditional logistic regression. There were a total of 497,996 children in the 2010 and 2011 Chilean live-birth cohorts. PCV10 VE was 11.2% (95%CI 8.5-13.6) when all pneumonia hospitalizations and deaths were used to define cases. VE increased to 20.7 (95%CI 17.3-23.8) when ICD10 codes used to denote viral pneumonia were excluded from the case definition. VE estimates on pneumonia deaths and all-cause deaths were 71.5 (95%CI 9.0-91.8) and 34.8 (95% CI 23.7-44.4), respectively. PCV10 vaccination substantially reduced the number of hospitalizations due to pneumonia and deaths due to pneumonia and to all-causes over this study period. Our findings also reinforce the importance of having quality health information systems for measuring VE.

  19. 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.

    Science.gov (United States)

    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-vaccine [Men-PS] in 2-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-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.

  20. 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.

  1. 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....

  2. Impact of pneumococcal vaccines use on invasive pneumococcal disease in Nunavik (Quebec from 1997 to 2010

    Directory of Open Access Journals (Sweden)

    Jean-Baptiste Le Meur

    2014-01-01

    Full Text Available Background: In 2000, an outbreak of severe pneumonia caused by a virulent clone of serotype 1 Streptococcus pneumoniae was detected in the Nunavik region of Quebec. A mass immunization campaign was implemented in the spring of 2002, targeting persons ≥5 years of age and using the 23-valent pneumococcal polysaccharide vaccine (PPSV23. At the same time, the 7-valent pneumococcal conjugate vaccine (PCV7 was introduced into the routine immunization programme of infants, with catch-up for children up to 4 years of age. Objectives: To describe the epidemiology of invasive pneumococcal disease (IPD in relation to PPSV23 and PCV7 use. Study design and methods: Retrospective analysis of IPD cases identified by the Quebec public health laboratory during the period 1997–2010. Results: A total of 82 IPD cases were identified during the study period. In adults, serotype 1 incidence decreased following the 2002 PPSV23 mass campaign but breakthrough cases continued to occur. Following PCV7 use in children, there was a decrease in the incidence of vaccine-type IPD and replacement by other serotypes in adults. In children, a marked decrease in the annual incidence of serotypes included in PCV7 was observed following PCV7 introduction: 162/100,000 in 1997–2001 vs. 10/100,000 in 2004–2010 (p<0.01. Concomitantly, the incidence of IPD caused by serotypes not included in PCV7 increased from 29/100,000 to 109/100,000 (p=0.11. Conclusion: The mass immunization campaign using the PPSV23 in 2002 and the introduction of PCV7 for the routine immunization of infants induced important modifications in the epidemiology of IPD. IPD rates in Nunavik remain much higher than in the southern part of the province both in children and adults. More effective pneumococcal vaccines are needed to eliminate geographic disparities in IPD risk.

  3. A phase 2 randomized controlled trial of a multicomponent meningococcal serogroup B vaccine, 4CMenB, in infants (II).

    Science.gov (United States)

    Esposito, Susanna; Prymula, Roman; Zuccotti, Gian Vincenzo; Xie, Fang; Barone, Michelangelo; Dull, Peter M; Toneatto, Daniela

    2014-01-01

    The licensed meningococcal serogroup B vaccine, 4CMenB (Bexsero(®)), contains recombinant membrane proteins (rMenB) and outer membrane vesicles (OMV) of the New Zealand serogroup B strain. We investigated whether reducing the OMV and/or protein content influences 4CMenB immunogenicity and reactogenicity in healthy two month-old infants. Six formulations were studied: 4CMenB, rMenB with 0, ¼ or ½ the OMV dose in 4CMenB, a half-dose of 4CMenB or a prelicensure formulation of 4CMenB, as a 4-dose primary/booster series, concomitantly with routine vaccines (DTaP-HBV-IPV/Hib and 7-valent pneumococcal conjugate) at 2, 3, 4 and 12 months of age. Immunogenicity was assessed as serum bactericidal activity measured with human complement (hSBA) against indicator strains for Men B vaccine antigens before and after the 2,3,4-month series and 12-month dose. Parents recorded solicited reactions for 7 days after each vaccination, and any adverse events throughout the study period. All formulations elicited robust immune response against rMenB components at 5 months, there was some evidence of OMV and protein dose-dependence for Men B indicator strains tested. Titers waned up to the 12-month dose, which elicited further strong responses, which were still OMV and protein dose-dependent. Groups with no, or low-dose OMV displayed slightly lower reactogenicity profiles, but all formulations were generally well-tolerated, high fever was rare and transient, and only three transient SAEs were considered possibly vaccine-related. Decreasing or removing the OMV content reduced reactogenicity of 4CMenB to a certain extent, but had an unacceptable negative impact on the immunogenicity profile. Trial: Clinicaltrials.gov NCT00937521.

  4. A phase II randomized controlled trial of a multicomponent meningococcal serogroup B vaccine, 4CMenB, in infants (II)

    Science.gov (United States)

    Esposito, Susanna; Prymula, Roman; Zuccotti, Gian Vincenzo; Xie, Fang; Barone, Michelangelo; Dull, Peter M; Toneatto, Daniela

    2014-01-01

    The licensed meningococcal serogroup B vaccine, 4CMenB (Bexsero®), contains recombinant membrane proteins (rMenB) and outer membrane vesicles (OMV) of the New Zealand serogroup B strain. We investigated whether reducing the OMV and/or protein content influences 4CMenB immunogenicity and reactogenicity in healthy two month-old infants. Six formulations were studied: 4CMenB, rMenB with 0, ¼ or ½ the OMV dose in 4CMenB, a half-dose of 4CMenB or a prelicensure formulation of 4CMenB, as a 4-dose primary/booster series, concomitantly with routine vaccines (DTaP-HBV-IPV/Hib and 7-valent pneumococcal conjugate) at 2, 3, 4 and 12 months of age. Immunogenicity was assessed as serum bactericidal activity measured with human complement (hSBA) against indicator strains for Men B vaccine antigens before and after the 2,3,4-month series and 12-month dose. Parents recorded solicited reactions for 7 days after each vaccination, and any adverse events throughout the study period. All formulations elicited robust immune response against rMenB components at 5 months, there was some evidence of OMV and protein dose-dependence for Men B indicator strains tested. Titers waned up to the 12-month dose, which elicited further strong responses, which were still OMV and protein dose-dependent. Groups with no, or low-dose OMV displayed slightly lower reactogenicity profiles, but all formulations were generally well-tolerated, high fever was rare and transient, and only three transient SAEs were considered possibly vaccine-related. Decreasing or removing the OMV content reduced reactogenicity of 4CMenB to a certain extent, but had an unacceptable negative impact on the immunogenicity profile. Trial: Clinicaltrials.gov NCT00937521 PMID:25424810

  5. Pneumococcal serotype distribution in adults with invasive disease and in carrier children in Italy: Should we expect herd protection of adults through infants' vaccination?

    Science.gov (United States)

    Azzari, Chiara; Cortimiglia, Martina; Nieddu, Francesco; Moriondo, Maria; Indolfi, Giuseppe; Mattei, Romano; Zuliani, Massimo; Adriani, Beatrice; Degl'Innocenti, Roberto; Consales, Guglielmo; Aquilini, Donatella; Bini, Giancarlo; Di Natale, Massimo Edoardo; Canessa, Clementina; Ricci, Silvia; de Vitis, Elisa; Mangone, Giusi; Bechini, Angela; Bonanni, Paolo; Pasinato, Angela; Resti, Massimo

    2016-01-01

    The 7-valent pneumococcal conjugate vaccine (PCV7) produced a significant herd protection in unvaccinated adult population mostly because of pneumococcus carriage decrease in vaccinated children. It is not known if the 13-valent pneumococcal vaccine can give similar effect on adults. Aims of the work were to evaluate whether the 6 additional serotypes are present in nasopharynx of children and serotype distribution in invasive pneumococcal infections (IPD) in adults. Realtime-PCR was used to evaluate pneumococcal serotypes in adults with confirmed IPD and in nasopharyngeal swabs (NP) from 629 children not vaccinated or vaccinated with PCV7 and resident in the same geographical areas. Two hundred twenty-one patients (116 males, median 67.9 years) with IPD were studied (pneumonia n = 103, meningitis n = 61 sepsis n = 50, other n = 7). Two hundred twelve were serotyped. The most frequent serotypes were 3, (31/212; 14.6%), 19A, (19/212; 9.0%), 12 (17/212; 8.0%), 7F, (14/212; 6.6%). In NP of children, the frequency of those serotypes causing over 50% of IPD in adults was very low, ranging from 0.48% for serotype 7F to 7.9% for serotype 19A. On the other side serotype 5, very frequent in NP (18.7%) caused children NP. We suggest that herd protection obtainable with the additional 6 serotypes included in PCV13 may be more limited than that demonstrated with PCV7 in the past. In order to reduce the burden of disease in adults, adults should be offered a specific vaccination program with highly immunogenic PCV.

  6. Serotype distribution of Streptococcus pneumoniae isolated from patients with invasive pneumococcal disease in Brazil before and after ten-pneumococcal conjugate vaccine implementation.

    Science.gov (United States)

    dos Santos, Silvia R; Passadore, Lilian F; Takagi, Elizabeth H; Fujii, Cristiane M; Yoshioka, Cristina R M; Gilio, Alfredo E; Martinez, Marina B

    2013-12-09

    The ten-pneumococcal conjugate vaccine (PCV10) was introduced into the national immunization program for childhood vaccination schedules by the Brazilian Health Public Service in March 2010. The aim of this study was to compare Streptococcus pneumoniae serotype distribution, antibiotic resistance patterns, and potential coverage before (January 2006-June 2010) and after (July 2010-September 2012) PCV10 introduction. The incidence of invasive pneumococcal disease (IPD), patient demographics, and disease characteristics were recorded. This study was conducted at the University Hospital of Sao Paulo University in Brazil from January 2006 to September 2012. Serotyping was performed using multiplex PCR typing, and antimicrobial sensitivity by Clinical and Laboratory Standards Institute (CLSI). A total of 259 S. pneumoniae strains were isolated from patients with IPD. The ages of the patients ranged from 3 months to 95 years old. The strains were isolated from cerebrospinal fluid, pleural fluid, and blood. The incidence of IPD among patients at HU-USP changed after the introduction of PCV10. The overall incidence of IPD was 3.42 cases per 1000 admissions in the vaccine pre- implementation period and of 2.99 cases per 1000 admissions in the vaccine post-implementation period. The incidence of IPD among children<2 y.o. attended at HU-USP changed significantly after the introduction of PCV10, from 20.30 to 3.97 of incidence. The incidence of PCV10- serotypes decrease from 16.47 to 0.44 in the same age, before and after PC10 implementation, respectively. Moreover, it was possible to realize the sensitivity to penicillin among isolates increased significantly in the post-vaccine period. Data from this study suggest that PCV10 contributed to decrease with PID rate among children less than 2 y.o. The resistance rate among pneumococcal isolates also could be observed since serotypes with greater resistance to beta lactam antibiotics were not easily isolated after vaccination.

  7. ACYW135群脑膜炎球菌多糖结合疫苗的研制%Development of groups ACYW135 meningococcal polysaccharide conjugate vaccine

    Institute of Scientific and Technical Information of China (English)

    张明华; 任涛; 曹欣; 唐秀丽; 韩菲; 王婷婷; 胡鹏; 张美香; 郝倩

    2013-01-01

    Objective To prepare a safe and effective quadrivalent meningococcal polysaccharide conjugate vaccine.Methods Groups A,C,Y and W135 meningococcal polysaccharide were activated by cyanogen bromide,respectively.With 1,6-adipic acid dihydrazide as linking agent,monovalent meningococcal polysaccharide conjugate vaccines were prepared by carbodiimide-mediated coupling of meningococcal polysaccharide with carrier protein diphtheria toxoid (DT),then groups ACYW135 meningococcal polysaccharide-DT conjugate vaccine (ACYW135-DT) was prepared by mixing each monovalent meningococcal polysaccharide conjugate vaccine in a certain proportion.Mice were immunized with ACYW135-DT,and antibodies to each polysaccharide were detected by indirect ELISA.The statistical analysis of the results were made by t test.Results Each index of the prepared ACYW135-DT achieved quality control standard.ACYW135-DT had a good safety and immunogenicity.The levels of IgG antibodies to group A (t =24.487,P<0.01),group C (t =17.056,P <0.01),group Y (t =26.213,P <0.01) and group W135 (t =17.392,P <0.01) polysaccharides in mice immunized with ACYW135-DT were significantly higher than those in mice immunized quadrivalent meningococcal polysaccharide vaccine.Conclusion ACYW135-DT is successfully prepared with this technology.%目的 制备安全有效的四价脑膜炎球菌多糖结合疫苗.方法 用溴化氰分别将A、C、Y、W135群脑膜炎球菌多糖活化,以己二酸二酰肼作为连接剂,碳化二亚胺作为偶联剂,先制备单价A、C、Y、W135群脑膜炎球菌多糖-白喉类毒素(diphtheria toxoid,DT)结合疫苗,再配比制成ACYW135群脑膜炎球菌多糖结合疫苗(groups ACYW135 meningococcal polysaccharide-DT conjugate vaccine,ACYW135-DT).以ACYW135-DT免疫小鼠,用间接ELISA检测小鼠血清抗各多糖抗体,采用t检验对检测结果进行统计学分析.结果 制备的ACYW135-DT的各项指标均达到质控标准,而且ACYW 135-DT具有良好

  8. 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.

  9. Effectiveness of the 13-valent pneumococcal conjugate vaccine against invasive pneumococcal disease in South African children: a case-control study.

    Science.gov (United States)

    Cohen, Cheryl; von Mollendorf, Claire; de Gouveia, Linda; Lengana, Sarona; Meiring, Susan; Quan, Vanessa; Nguweneza, Arthermon; Moore, David P; Reubenson, Gary; Moshe, Mamokgethi; Madhi, Shabir A; Eley, Brian; Hallbauer, Ute; Finlayson, Heather; Varughese, Sheeba; O'Brien, Katherine L; Zell, Elizabeth R; Klugman, Keith P; Whitney, Cynthia G; von Gottberg, Anne

    2017-03-01

    The 13-valent pneumococcal conjugate vaccine (PCV13) was designed to include disease-causing serotypes that are important in low-income and middle-income countries. Vaccine effectiveness estimates are scarce in these settings. South Africa replaced PCV7 with PCV13 in 2011 using a 2 + 1 schedule. We aimed to assess the effectiveness of two or more doses of PCV13 against invasive pneumococcal disease in children with HIV infection and in those not infected with HIV. Cases of invasive pneumococcal disease in children aged 5 years or younger were identified through national laboratory-based surveillance. Isolates were serotyped with the Quellung reaction or PCR. We sought in-hospital controls for every case, matched for age, HIV status, and study site. We aimed to enrol four controls for every case not infected with HIV and six controls for every case with HIV infection (case-control sets). With conditional logistic regression, we calculated vaccine effectiveness as a percentage, with the equation 1 - [adjusted odds ratio for vaccination] × 100. We included data from an earlier investigation of PCV7 to assess vaccine effectiveness in children exposed to but not infected with HIV and in malnourished children not infected with HIV. Between January, 2012, and December, 2014, we enrolled children aged 16 weeks or older to our study: 240 were cases not infected with HIV, 75 were cases with HIV infection, 1118 were controls not infected with HIV, and 283 were controls with HIV infection. The effectiveness of two or more doses of PCV13 against PCV13-serotype invasive pneumococcal disease was 85% (95% CI 37 to 96) among 11 case-control sets of children not infected with HIV and 91% (-35 to 100) among three case-control sets of children with HIV infection. PCV13 effectiveness among 26 case-control sets of children not infected with HIV was 52% (95% CI -12 to 79) against all-serotype invasive pneumococcal disease and 94% (44 to 100) for serotype 19A. Vaccine

  10. 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% (presistant strains, which was initially 23% in both populations, decreased significantly in EJ, to 10%, while simultaneously it increased in PA to 33% (presistance 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 decreased and were replaced by non-VT13 strains, which were mostly not antibiotic resistant, resulting in a net decrease in antibiotic resistance. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Streptococcus pneumoniae oropharyngeal colonization in school-age children and adolescents with type 1 diabetes mellitus: Impact of the heptavalent pneumococcal conjugate vaccine.

    Science.gov (United States)

    Principi, Nicola; Iughetti, Lorenzo; Cappa, Marco; Maffeis, Claudio; Chiarelli, Franco; Bona, Gianni; Gambino, Monia; Ruggiero, Luca; Patianna, Viviana; Matteoli, Maria Cristina; Marigliano, Marco; Cipriano, Paola; Parlamento, Silvia; Esposito, Susanna

    2016-01-01

    This study evaluated Streptococcus pneumoniae colonization in children and adolescents with type 1 diabetes mellitus (DM1) to investigate the theoretical risk of invasive pneumococcal disease (IPD) in these patients and the potential protective efficacy of pneumococcal conjugate vaccines (PCVs). An oropharyngeal swab was obtained from 299 patients aged 6-17 y with DM1 who were enrolled during routine clinical visits. DNA from swabs was analyzed for S. pneumoniae using real-time polymerase chain reaction. S. pneumoniae was identified in the swabs of 148 subjects (49.8%). Colonization was strictly age-related and declined significantly in the group aged ≥15 years (odds ratio [OR] 0.28; 95% confidence interval [CI], 0.14-0.57). Carriage was also significantly influenced by sex (lower in females: OR 0.56; 95% CI, 0.35-0.91), ethnicity (less common among non-Caucasians: OR 0.34; 95% CI, 0.13-0.89), parental smoking habit (more frequent among children with at least one smoker between parents: OR 1.76; 95% CI, 0.90-2.07), and the administration of antibiotic therapy in the previous 3 months (less frequent among patients who received antibiotics: OR 0.21; 95% CI, 0.07-0.62). Multivariate analyses of the entire study population showed no association between carriage and PCV7 vaccination status. Serotypes 19F, 9V, and 4 were the most frequently identified serotypes. In conclusion, school-age children and adolescents with DM1 are frequently colonized by S. pneumoniae, and protection against pneumococcal carriage following infant and toddler vaccination was not effective after several years. Together with the need to increase vaccine uptake in all the children aged <2 years, these results suggest that PCV booster doses are needed in DM1 patients to maintain the protection offered by these vaccinations.

  12. Impact of fibrinolytics on the outcome of empyema in South African ...

    African Journals Online (AJOL)

    introduction of 7-valent pneumococcal conjugate vaccine (PCV7), the incidence of ... after the child received fibrinolytics were included in the treatment analysis. ... pleural effusion causing symptoms (pain ... Persistent fever >38°C more than.

  13. 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

  14. Preparation and immunochemical characterization of meningococcal group C polysaccharide-tetanus toxoid conjugates as a new generation of vaccines.

    OpenAIRE

    Beuvery, E.C.; Miedema, F; Van Delft, R.; Haverkamp, J.

    1983-01-01

    Neisseria meningitidis group C polysaccharide-tetanus toxoid conjugates have been prepared by using high-molecular-weight polysaccharide and purified tetanus toxoid and 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide as a coupling reagent. The influence of three conditions of preparation was studied. Biochemical assays, the enzyme-linked immunosorbent assay, and isopycnic CsCl gradient ultracentrifugation have been used to characterize the conjugates. The polysaccharide-to-protein ratios of th...

  15. Estimates on state-specific Pneumococcal Conjugate Vaccines (PCV coverage in the private sector in the year 2012: Evidence from PCV utilization data

    Directory of Open Access Journals (Sweden)

    Habib Hasan Farooqui

    2016-01-01

    Full Text Available The pneumococcal conjugate vaccine (PCV is not available through universal immunization programs but is available through private healthcare providers. Because the PCV coverage rates are unknown, we developed a Microsoft Excel-based coverage assessment model to estimate state-specific PCV coverage for the year 2012. Our findings suggest that in the private sector, the "overall PCV coverage" was around 0.33% that ranged between a minimum of 0.07% for Assam, India and a maximum of 2.38% for Delhi, India. Further, in major metropolitan areas, overall PCV coverage rates were: 2.28% for Delhi, India, 13.31% for Mumbai (Maharashtra, India 0.76% for Lucknow (Uttar Pradesh, India, 1.93% for Kolkata (West Bengal, India, and 4.92% for Chennai (Tamil Nadu, India highlighting that urban centers are major drivers for PCV utilization driver in the states with high PCV consumption. Hence, to improve PCV coverage, both demand side (increasing consumer awareness about pneumonia prevention and supply side (controlling vaccine prices and indigenous vaccine production interventions are required.

  16. 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.

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

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    Palmu, Arto A.; Rinta-Kokko, Hanna; Nohynek, Hanna; Nuorti, J. Pekka; Kilpi, Terhi M.; Jokinen, Jukka

    2017-01-01

    Background 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. Methods 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. Results 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. Conclusions A substantial decrease in pneumonia rates was observed both among

  18. 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).

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    Libwea, John Njuma; Kobela, Marie; Ollgren, Jukka; Emah, Irene; Tchio, Robert; Nohynek, Hanna

    2014-01-01

    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. 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. 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. 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 the PCV-13 is to reach every child.

  19. Vacinas meningocócicas conjugadas: eficácia e novas combinações Meningococcal conjugate vaccines: efficacy and new combinations

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    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

  20. Evaluation of a LPS-based glycoconjugate vaccine against bovine Escherichia coli mastitis: Formation of LPS Abs in cows after immunization with E. coli core oligosaccharides conjugated to hemocyanine.

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    Brade, Lore; Hensen, Selma; Brade, Helmut

    2013-01-01

    The immune response of cows against the core oligosaccharide of Escherichia coli rough mutants (core types R1-R4, K-12 and J-5) was investigated after immunization with a synthetic glycoconjugate composed of deacylated LPS conjugated to hemocyanine (22 animals). Ab formation was measured by ELISA using LPS or deacylated LPS conjugated to BSA as an Ag. The glycoconjugate immunogens were used to vaccinate cows (36 animals), which were then challenged intramammarily with E. coli O 157 (K1 negative, R1 core type). Compared with control groups no protection was observed, although high titers against the R1 core type were detected in vaccinated animals. Western blots using the immune sera showed that the Ab response was directed against the core region and not against the O-antigen, which may explain the failure of the vaccine.

  1. 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.

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    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.

  2. La vacuna neumocócica conjugada heptavalente (Prevenar™: Diferencias en su efectividad en distintas poblaciones Heptavalent-pneumococcal conjugate vaccine (Prevenar™: Differences in effectiveness between populations

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    M. Guevara

    2008-08-01

    Full Text Available En el presente trabajo se revisan las publicaciones sobre la efectividad de la vacuna neumocócica conjugada heptavalente (VNC7v en la prevención de enfermedad neumocócica invasiva (ENI en niños menores de 5 años. También se analizan las características de la vacuna y su impacto en la epidemiología de la ENI en distintos lugares. Antes de la introducción de la VNC7v el porcentaje de casos de ENI debidos a serogrupos vacunales oscilaba entre el 89% en Estados Unidos y el 43% en Asia. En España era del 68%. La vigilancia activa basada en laboratorios demuestra que la introducción de la VNC7v ha tenido un impacto muy variable en la incidencia de ENI, con descensos que oscilan entre el 91% en Estados Unidos y el 12% en Navarra, España. La efectividad global de la VNC7v en trabajos publicados va desde el 31% al 89%, dependiendo principalmente de los patrones de serotipos de neumococo predominantes en cada lugar. Numerosos estudios demuestran una capacidad variable de reemplazo del neumococo, que hace que el efecto de la vacuna pueda verse mermado, al ir ocupando los serotipos no vacunales el lugar dejado por los vacunales. Un estudio en Navarra ha encontrado un riesgo de ENI por serogrupos no vacunales 6 veces mayor en los niños vacunados que en los no vacunados. En lugares donde menos del 70% de los serotipos causantes de ENI están representados en la VNC7v, la efectividad de su introducción en el calendario vacunal será probablemente escasa y el reemplazo de serotipos rápido. En estos casos la VNC7v podría reservarse para niños con factores de riesgo para ENI.This article reviews the publications on the effectiveness of heptavalent-pneumococcal conjugate vaccine (PCV7 in the prevention of invasive pneumococcal disease (IPD in children under five years of age. It also analyses the characteristics of the vaccine and its impact on the epidemiology of IPD in different places. Before the introduction of PCV7, the percentage of cases of

  3. Efficacy of pneumococcal nontypable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV in young Latin American children: A double-blind randomized controlled trial.

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    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. Anti-nicotine vaccines: Comparison of adjuvanted CRM197 and Qb-VLP conjugate formulations for immunogenicity and function in non-human primates.

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    McCluskie, Michael J; Thorn, Jennifer; Gervais, David P; Stead, David R; Zhang, Ningli; Benoit, Michelle; Cartier, Janna; Kim, In-Jeong; Bhattacharya, Keshab; Finneman, Jari I; Merson, James R; Davis, Heather L

    2015-12-01

    Anti-nicotine vaccines comprise nicotine-like haptens conjugated to a carrier protein plus adjuvant(s). Unfortunately, those tested clinically have failed to improve overall long term quit rates. We had shown in mice that carrier, hapten, linker, hapten load (number of haptens per carrier molecule), aggregation and adducts, as well as adjuvants influence the function of antibodies (Ab) induced. Herein, we tested an optimized antigen, NIC7-CRM, comprised of 5-aminoethoxy-nicotine (NIC7) conjugated to genetically detoxified diphtheria toxin (CRM197), with hapten load of ~16, no aggregation (~100% monomer) and minimal adducts. NIC7-CRM was tested in non-human primates (NHP) and compared to NIC-VLP, which has the same hapten and carrier as the clinical-stage CYT002-NicQb but a slightly different linker and lower hapten load. With alum as sole adjuvant, NIC7-CRM was superior to NIC-VLP for Ab titer, avidity and ex vivo function (83% and 27% nicotine binding at 40ng/mL respectively), but equivalent for in vivo function after intravenous [IV] nicotine challenge (brain levels reduced ~10%). CpG adjuvant added to NIC7-CRM/alum further enhanced the Ab responses and both ex vivo function (100% bound) and in vivo function (~80% reduction in brain). Thus, both optimal antigen design and CpG adjuvant were required to achieve a highly functional vaccine. The compelling NHP data with NIC7-CRM with alum/CpG supported human testing, currently underway.

  5. 10-valent pneumococcal non-typeable Haemophilus influenzae protein-D conjugate vaccine (PHiD-CV) induces memory B cell responses in healthy Kenyan toddlers.

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    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 < 0·01), 19F (21-66%; P < 0·01) and 23F (13-36%; P = 0·02), but not serotypes 6B (24-42%; P = 0·24) and 14 (21-40%; P = 0·06). Correlations between antibodies and 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 < 0·01; day 210: non-carriers, 72% versus carriers, 33%, P = 0·07). PHiD-CV is capable of inducing memory B cells against some of the component pneumococcal capsular polysaccharides.

  6. Pharmacoeconomic aspects related to the 13-valent pneumococcal conjugate vaccine: preliminary analysis of the data from the ASL of Viterbo

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    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. [Invasive infections caused by Haemophilus influenzae type b after the institution of the conjugated vaccine on the expanded programm on immunization in Chile].

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    Cruces R, Pablo; Donoso F, Alejandro; Camacho A, Jorge; Llorente H, Marcela

    2006-03-01

    After almost a decade since the introduction of Haemophilus influenzae type b (Hib) conjugate vaccines in Chile (in a 2-4-6 month schedule), Hib invasive infections have dramatically decreased, albeit they remain to occasionally produce disease in pediatric patients. We report our experience with children whom developed Hib invasive disease in children since 2000 to 2004. Medical records of children with Hib were reviewed in order to describe the epidemiology, main clinical and laboratory findings, management and complications. Twenty three patients (17 male), between 1 and 71 months (median 30 months) were identified: pneumonia (7), meningitis (4), pleuropneumonia (2), empyema (2), sepsis (2), cellulitis (2), meningitis and pleuropneumonia (1), purpura fulminans (1), miositis (1) and epiglottitis (1). No deaths were observed and four patients presented severe sequelae at hospital discharge. Twenty patients were considered vaccine failures. Hib remains as a sporadic cause of severe disease in Chile and thus for physicians should still keep it in mind. Case analysis and active surveillance are necessary to monitor the current immunization regimen.

  8. Immunization and chemical conjugation of Bm95 obtained from Pichia pastoris enhances the immune response against vaccinal protein and Neisseria meningitidis capsular polysaccharide

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    Rodriguez-Valle M

    2014-03-01

    Full Text Available Manuel Rodriguez-Valle,1 Leonardo Canan-Hadden,2 Olivia Niebla2 1Animal Biotechnology Division, 2Analytical Division, Centre for Genetic Engineering and Biotechnology, Havana, Cuba Abstract: The ectoparasite Rhipicephalus (Boophilus microplus causes severe economic losses to the cattle industry in tropical and subtropical regions, and transmits endoparasites, such as Babesia bovis. The glycoprotein Bm95 is homologous to Bm86, a surface membrane protein of gut epithelial cells in R. microplus, and has been shown to efficiently control this ectoparasite in regions of the Americas. The immunostimulant properties of Bm86 have already been demonstrated after its coinjection with hepatitis B surface antigen (HBsAg and the infectious bovine rhinotracheitis virus. This study evaluated the carrier and immunostimulant properties of Bm95 using low immunogenic Neisseria meningitidis capsular C polysaccharide (Men CpS and HBsAg. We produced two polysaccharide-Bm95 conjugates by carbodiimide (MenCpSBm-c and reductive amination (MenCpSBm-ra methods. These conjugates were characterized and evaluated in mice. Antibody titers against Men CpS were significantly higher in mice immunized with MenCpSBm-ra (2,350±250, P<0.01 than in those immunized with MenCpSBm-c (250±75 or Men CpS (570±104. The study data indicate effective immunological memory after booster inoculation in mice immunized with MenCpSBm-ra. Additionally, significant humoral immunity against HBsAg was documented in mice coimmunized via the intranasal route with recombinant Bm95 (11,400±345 and HBsAg (128,000±250 compared with mice immunized only with HBsAg (400±40 or Bm95 (5,461±150, P<0.01. In conclusion, the immunostimulatory properties of recombinant Bm95 make it a useful element for developing safer conjugated vaccines against bacterial pathogens and for evaluation against ticks and tick-borne diseases in the context of a polyvalent veterinary vaccine. Keywords: glycoconjugate, Bm86

  9. The data management of a phase III efficacy trial of an 11-valent pneumococcal conjugate vaccine and related satellite studies conducted in the Philippines

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    Sanvictores Diozele Hazel M

    2012-06-01

    Full Text Available Abstract Background A large phase III placebo-controlled, randomized efficacy trial of an investigational 11-valent pneumococcal conjugate vaccine against pneumonia in children less than 2 years of age was conducted in the Philippines from July 2000 to December 2004. Clinical data from 12,194 children who were given either study vaccine or placebo was collected from birth up to two years of age for the occurrence of radiologically proven pneumonia as the primary endpoint, and for clinical pneumonia and invasive pneumococcal disease as the secondary endpoints. Several tertiary endpoints were also explored. Along the core trial, several satellite studies on herd immunity, cost-effectiveness of the study vaccine, acute otitis media, and wheezing were conducted. Results We describe here in detail how the relevant clinical records were managed and how quality control procedures were implemented to ensure that valid data were obtained respectively for the core trial and for the satellite studies. We discuss how the task was achieved, what the challenges were and what might have been done differently. Conclusions There were several factors that made the task of data management doable and efficient. First, a pre-trial data management system was available. Secondly, local committed statisticians, programmers and support staff were available and partly familiar to clinical trials. Thirdly, the personnel had undergone training during trial and grew with the task they were supposed to do. Thus the knowledge needed to develop and operate clinical data system was fully transferred to local staff. Trial registration Current Controlled Trials ISRCTN62323832

  10. 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.

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    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.

  11. 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.

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    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.

  12. 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.

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    Susan Meiring

    Full Text Available Streptococcus pneumoniae is the commonest cause of bacteremic pneumonia among HIV-infected persons. As more countries with high HIV prevalence are implementing infant pneumococcal conjugate vaccine (PCV programs, we aimed to describe the baseline clinical characteristics of adult invasive pneumococcal disease (IPD in the pre-PCV era in South Africa in order to interpret potential indirect effects following vaccine use.National, active, laboratory-based surveillance for IPD was conducted in South Africa from 1 January 2003 through 31 December 2008. At 25 enhanced surveillance (ES hospital sites, clinical data, including HIV serostatus, were collected from IPD patients ≥ 5 years of age. We compared the clinical characteristics of individuals with IPD in those HIV-infected and -uninfected using multivariable analysis. PCV was introduced into the routine South African Expanded Program on Immunization (EPI in 2009.In South Africa, from 2003-2008, 17 604 cases of IPD occurred amongst persons ≥ 5 years of age, with an average incidence of 7 cases per 100 000 person-years. Against a national HIV-prevalence of 18%, 89% (4190/4734 of IPD patients from ES sites were HIV-infected. IPD incidence in HIV-infected individuals is 43 times higher than in HIV-uninfected persons (52 per 100 000 vs. 1.2 per 100 000, with a peak in the HIV-infected elderly population of 237 per 100 000 persons. Most HIV-infected individuals presented with bacteremia (74%, 3 091/4 190. HIV-uninfected individuals were older; and had more chronic conditions (excluding HIV than HIV-infected persons (39% (210/544 vs. 19% (790/4190, p<0.001. During the pre-PCV immunization era in South Africa, 71% of serotypes amongst HIV-infected persons were covered by PCV13 vs. 73% amongst HIV-uninfected persons, p = 0.4, OR 0.9 (CI 0.7-1.1.Seventy to eighty-five percent of adult IPD in the pre-PCV era were vaccine serotypes and 93% of cases had recognized risk factors (including HIV-infection for

  13. Direct Comparison of Immunogenicity Induced by 10- or 13-Valent Pneumococcal Conjugate Vaccine around the 11-Month Booster in Dutch Infants.

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    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

  14. Direct, indirect and total effects of 13-valent pneumococcal conjugate vaccination on invasive pneumococcal disease in children in Navarra, Spain, 2001 to 2014: cohort and case-control study.

    Science.gov (United States)

    Guevara, Marcela; Barricarte, Aurelio; Torroba, Luis; Herranz, Mercedes; Gil-Setas, Alberto; Gil, Francisco; Bernaola, Enrique; Ezpeleta, Carmen; Castilla, Jesús

    2016-01-01

    We estimated the direct, indirect and total effects of the 13-valent pneumococcal conjugate vaccine (PCV13) on invasive pneumococcal disease (IPD) in children. A population-based cohort study followed children aged between 2.5 and 59 months between 2001 and 2014 in Navarra, Spain. IPD incidence was compared by PCV status and period. All cases diagnosed from July 2010 to December 2014 and eight matched controls per case were analysed to estimate the adjusted direct effect of PCV13. A total of 120,980 children were followed and 206 IPD cases were detected. Compared with unvaccinated children in the baseline period (2001-2004), overall IPD incidence in 2011-2014 (76% average PCV coverage) declined equally in vaccinated (total effect: 76%; hazard ratio (HR): 0.24; 95% confidence interval (CI): 0.14-0.40) and unvaccinated children (indirect effect: 78%; HR: 0.22; 95% CI: 0.09-0.55). IPD incidence from non-PCV13 serotypes increased among vaccinated children (HR: 2.84; 95% CI: 1.02-7.88). The direct effect of one or more doses of PCV13 against vaccine serotypes was 95% (odds ratio: 0.05; 95% CI: 0.01-0.55). PCV13 was highly effective in preventing vaccine-serotype IPD. The results suggest substantial and similar population-level vaccine benefits in vaccinated and unvaccinated children through strong total and indirect effects.

  15. Antigen processing of glycoconjugate vaccines; the polysaccharide portion of the pneumococcal CRM(197) conjugate vaccine co-localizes with MHC II on the antigen processing cell surface.

    Science.gov (United States)

    Lai, Zengzu; Schreiber, John R

    2009-05-21

    Pneumococcal (Pn) polysaccharides (PS) are T-independent (TI) antigens and do not induce immunological memory or antibodies in infants. Conjugation of PnPS to the carrier protein CRM(197) induces PS-specific antibody in infants, and memory similar to T-dependent (Td) antigens. Conjugates have improved immunogenicity via antigen processing and presentation of carrier protein with MHC II and recruitment of T cell help, but the fate of the PS attached to the carrier is unknown. To determine the location of the PS component of PnPS-CRM(197) in the APC, we separately labeled PS and protein and tracked their location. The PS of types 14-CRM(197) and 19F-CRM(197) was specifically labeled by Alexa Fluor 594 hydrazide (red). The CRM(197) was separately labeled red in a reaction that did not label PS. Labeled antigens were incubated with APC which were fixed, permeabilized and incubated with anti-MHC II antibody labeled green by Alexa Fluor 488, followed by confocal microscopy. Labeled CRM(197) was presented on APC surface and co-localized with MHC II (yellow). Labeled unconjugated 14 or 19F PS did not go to the APC surface, but PS labeled 14-CRM(197) and 19F-CRM(197) was internalized and co-localized with MHC II. Monoclonal antibody to type 14 PS bound to intracellular type 14 PS and PS-CRM(197). Brefeldin A and chloroquine blocked both CRM(197) and PS labeled 14-CRM(197) and 19F-CRM(197) from co-localizing with MHC II. These data suggest that the PS component of the CRM(197) glycoconjugate enters the endosome, travels with CRM(197) peptides to the APC surface and co-localizes with MHC II.

  16. Pneumococcal vaccination and otitis media in Australian Aboriginal infants: comparison of two birth cohorts before and after introduction of vaccination

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    Mackenzie Grant

    2009-02-01

    Full Text Available Abstract Background Aboriginal children in remote Australia have high rates of complicated middle ear disease associated with Streptococcus pneumoniae and other pathogens. We assessed the effectiveness of pneumococcal vaccination for prevention of otitis media in this setting. Methods We compared two birth cohorts, one enrolled before (1996–2001, and the second enrolled after introduction of 7-valent pneumococcal conjugate and booster 23-valent polysaccharide vaccine (2001–2004. Source populations were the same for both cohorts. Detailed examinations including tympanometry, video-recorded pneumatic otoscopy and collection of discharge from tympanic membrane perforations, were performed as soon as possible after birth and then at regular intervals until 24 months of life. Analyses (survival, point prevalence and incidence were adjusted for confounding factors and repeated measures with sensitivity analyses of differential follow-up. Results Ninety-seven vaccinees and 51 comparison participants were enrolled. By age 6 months, 96% (81/84 of vaccinees and 100% (41/41 of comparison subjects experienced otitis media with effusion (OME, and by 12 months 89% and 88% experienced acute otitis media (AOM, 34% and 35% experienced tympanic membrane perforation (TMP and 14% and 23% experienced chronic suppurative otitis media (CSOM. Age at the first episode of OME, AOM, TMP and CSOM was not significantly different between the two groups. Adjusted incidence of AOM (incidence rate ratio: 0.88 [95% confidence interval (CI: 0.69–1.13] and TMP (incidence rate ratio: 0.63 [0.36–1.11] was not significantly reduced in vaccinees. Vaccinees experienced less recurrent TMP, 9% (8/95 versus 22% (11/51, (odds ratio: 0.33 [0.11–1.00]. Conclusion Results of this study should be interpreted with caution due to potential bias and confounding. It appears that introduction of pneumococcal vaccination among Aboriginal infants was not associated with significant changes

  17. Opposite effects of actively and passively acquired immunity to the carrier on responses of human infants to a Haemophilus influenzae type b conjugate vaccine

    DEFF Research Database (Denmark)

    Barington, T; Gyhrs, A; Kristensen, Kim

    1994-01-01

    factors influencing the antibody response to conjugate vaccines are needed. In this study, the response to HibCP coupled to tetanus toxoid (TT) was examined in relation to (i) priming with or coadministration of the carrier protein and (ii) the levels of passively acquired maternal TT antibodies. One...... than infants with low prevaccination levels after the first (P = 0.0001) and the second (P = 0.01) doses of HibCP-TT. In contrast, active priming with TT at 4 months resulted in a threefold-higher median level of anti-HibCP (group C; 1.34 micrograms/ml) than in the unprimed group (group A; 0.......40 microgram/ml) after the first dose of HibCP-TT (P = 0.01). Coadministration of TT had no enhancing effect (group B; 0.58 microgram/ml). No significant differences between the median anti-HibCP levels were seen after the second HibCP-TT dose (6.72, 9.63, and 11.44 micrograms/ml in groups A, B, and C...

  18. 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

    Children with recurrent lower respiratory tract infection (RLRI) may respond poorly to polysaccharide antigens. To examine how such children respond to a polysaccharide coupled to a protein carrier, we immunized 15 children with RLRI aged 8-69 months and 15 carefully age-matched healthy controls ......M response to Hib conjugate vaccine in these children, since this isotype predominates in the primary immune response, i.e., in the absence of immunologic memory.(ABSTRACT TRUNCATED AT 250 WORDS)......Children with recurrent lower respiratory tract infection (RLRI) may respond poorly to polysaccharide antigens. To examine how such children respond to a polysaccharide coupled to a protein carrier, we immunized 15 children with RLRI aged 8-69 months and 15 carefully age-matched healthy controls.......005), whereas 1 month later they had significantly more IgM antibody (P = 0.038). No other significant differences were found between the groups before or after immunization with respect to antipolysaccharide Hib antibodies. Since naturally occurring IgG antibodies are thought to be acquired partly...

  19. Safety and immunogenocity of a novel combined Haemophilus influenzae type b-Neisseria meningitidis serogroups A and C-tetanus-toxoid conjugate vaccine in healthy Chinese children aged 6 months to 5 years old.

    Science.gov (United States)

    Hu, Jian-li; Tao, Hong; Li, Jing-xin; Dai, Wei-ming; Song, Bin; Sun, Jin-fang; Liu, Pei; Tang, Jie; Liu, Wen-yu; Wang, Shi-yuan; Zhu, Feng-cai

    2015-01-01

    A novel combined Haemophilus influenzae type b-Neisseria meningitidis serogroups A and C-tetanus-toxoid conjugate vaccine (Hib-MenAC vaccine) has been developed to protect children against diseases caused by Hib, MenA, and MenC. This study investigated the safety and immunogenicity of the Hib-MenAC vaccine administered in 2-dose series to children aged 6-23 months and in a single dose to children aged 2-5 y. A randomized, positive-controlled, non-inferiority clinical trial was conducted for 1200 healthy participants in each age group. Within each age group, participants were randomly allocated to the Hib-MenAC group or the control group at a ratio of 1:1. Adverse reactions were recorded within 28 d after each dose. Blood samples were obtained to assess immunogenicity on day 0 and at 28 d after a complete vaccination course. For the investigational vaccine, the incidence of total adverse reactions in vaccinees aged 6-23 months was 46.8% and that in vaccinees aged 2-5 y was 29.8%. Most adverse reactions were mild or moderate. One non-fatal serious adverse event occurred in the Hib-MenAC group, but was unrelated to vaccination. The seroconversion rate to the 3 components reached 94.0%, and the proportion of vaccinees with rSBA titers ≥ 1:8 and PRP ≥ 0.15 g/mL reached 97.0% in both age groups. The safety and immunogenicity of the Hib-MenAC vaccine were non-inferior when compared to the licensed vaccines. It was concluded that the novel vaccine would be expected to protect children against all of the targeted diseases.

  20. The first dose of a Haemophilus influenzae type b conjugate vaccine reactivates memory B cells: evidence for extensive clonal selection, intraclonal affinity maturation, and multiple isotype switches to IgA2

    DEFF Research Database (Denmark)

    Hougs, L; Juul, L; Ditzel, H J

    1999-01-01

    The Ab response of a healthy adult to the first dose of a Haemophilus influenzae type b capsular polysaccharide (HibCP) conjugate vaccine was studied at the level of Ig gene usage by circulating Ab-secreting cells. Forty-one IgA and 17 IgG mRNA sequences were obtained. The major part of the respo......The Ab response of a healthy adult to the first dose of a Haemophilus influenzae type b capsular polysaccharide (HibCP) conjugate vaccine was studied at the level of Ig gene usage by circulating Ab-secreting cells. Forty-one IgA and 17 IgG mRNA sequences were obtained. The major part...... selected, and expanded population of cells existing before vaccination, i.e., memory B cells. The dominating heavy and light chains of the response were combined in a Fab that bound HibCP. It was shown that the shared heavy and light chain mutations increased the affinity for HibCP considerably, indicating...... that the clonal selection had been driven by affinity. Pre-existing memory cells in unvaccinated adults may explain several features of Ab responses to polysaccharide vaccines and may play a role in acquiring the ability to respond to pure polysaccharides during infancy....

  1. b型流感嗜血杆菌结合疫苗接种反应及其处理%Adverse reactions after inoculation of Haemophilus influenzae type b conjugate vaccine and their treatment principles

    Institute of Scientific and Technical Information of China (English)

    樊永贞

    2014-01-01

    Haemophilus influenzae type b (Hib) conjugate vaccine belongs to category Ⅱ vaccine in China.Safety of Hib vaccine is good,and incidence rate of adverse reactions after Hib vaccination is low.Normal reactions after Hib vaccination include local redness,swelling and pain,and mild fever,etc.These symptoms can disappear spontaneously without treatment.Abnormal reactions after Hib vaccination include local blisters and suppuration,systemic allergic rashes and purpura,gastrointestinal reactions,and emotional abnormality,etc.These abnormal reactions can be recovered well after proper treatment.%b型流感嗜血杆菌(Haemophilus in fluenzae type b,Hib)疫苗在中国属于二类疫苗,其安全性良好,接种反应发生率低.Hib疫苗接种后的一般反应包括局部红肿、疼痛,低热等,无需处理可自愈.Hib疫苗接种后的异常反应包括局部水泡和化脓、全身过敏性皮疹和紫癜、消化道反应、情绪异常等,这些异常反应经对症治疗可得到恢复.

  2. PNEUMOCOCCAL INFECTION — IN THE CENTRE OF ATTENTION AGAIN

    Directory of Open Access Journals (Sweden)

    S.V. Sidorenko

    2009-01-01

    Full Text Available This article present a general review on pneumococcal infection, its prevalence, clinic types in children in Russia and worldwide. Description of S. pneumoniae serotypes' distribution and its influence at clinical manifestation of pneumococcal infection and vaccination effectiveness is provided. Author evaluates perspectives of pneumococcal infection prevention by vaccination with pneumococcal conjugated 7-valent vaccine in Russia.Key words: children, pneumococcal infection, vaccination, pneumococcal conjugated 7 valent vaccine.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2009;8(3:82-87

  3. Economic Evaluation of Immunisation Programme of 23-Valent Pneumococcal Polysaccharide Vaccine and the Inclusion of 13-Valent Pneumococcal Conjugate Vaccine in the List for Single-Dose Subsidy to the Elderly in Japan.

    Directory of Open Access Journals (Sweden)

    Shu-ling Hoshi

    Full Text Available Currently in Japan, both 23-valent pneumococcal polysaccharide vaccine (PPSV-23 and 13-valent pneumococcal conjugate vaccine (PCV-13 are available for the elderly for the prevention of S. pneumoniae-related diseases. PPSV-23 was approved in 1988, while the extended use of PCV-13 was approved for adults aged 65 and older in June 2014. Despite these two vaccines being available, the recently launched national immunisation programme for the elderly only subsidised PPSV-23. The framework of the current immunisation programme lasts for five years. The elderly population eligible for the subsidised PPSV-23 shot for the 1st year are those aged 65, 70, 75, 80, 85, 90, 95 and ≥ 100. While from the 2nd year to the 5th year, those who will age 65, 70, 75, 80, 85, 90, 95 and 100 will receive the same subsidised shot.We performed economic evaluations to (1 evaluate the efficiency of alternative strategies of PPSV-23 single-dose immunisation programme, and (2 investigate the efficiency of PCV-13 inclusion in the list for single-dose pneumococcal vaccine immunisation programme. Three alternative strategies were created in this study, namely: (1 current PPSV-23 strategy, (2 65 to 80 (as "65-80 PPSV-23 strategy", and (3 65 and older (as "≥ 65 PPSV-23 strategy". We constructed a Markov model depicting the S. pneumoniae-related disease course pathways. The transition probabilities, utility weights to estimate quality adjusted life year (QALY and disease treatment costs were either calculated or cited from literature. Cost of per shot of vaccine was ¥ 8,116 (US$74; US$1 = ¥ 110 for PPSV-23 and ¥ 10,776 (US$98 for PCV-13. The model runs for 15 years with one year cycle after immunisation. Discounting was at 3%.Compared to current PPSV-23 strategy, 65-80 PPSV-23 strategy cost less but gained less, while the incremental cost-effectiveness ratios (ICERs of ≥ 65 PPSV-23 strategy was ¥ 5,025,000 (US$45,682 per QALY gained. PCV-13 inclusion into the list for

  4. Economic Evaluation of Immunisation Programme of 23-Valent Pneumococcal Polysaccharide Vaccine and the Inclusion of 13-Valent Pneumococcal Conjugate Vaccine in the List for Single-Dose Subsidy to the Elderly in Japan

    Science.gov (United States)

    Hoshi, Shu-ling; Kondo, Masahide; Okubo, Ichiro

    2015-01-01

    Background Currently in Japan, both 23-valent pneumococcal polysaccharide vaccine (PPSV–23) and 13-valent pneumococcal conjugate vaccine (PCV–13) are available for the elderly for the prevention of S. pneumoniae-related diseases. PPSV–23 was approved in 1988, while the extended use of PCV–13 was approved for adults aged 65 and older in June 2014. Despite these two vaccines being available, the recently launched national immunisation programme for the elderly only subsidised PPSV–23. The framework of the current immunisation programme lasts for five years. The elderly population eligible for the subsidised PPSV–23 shot for the 1st year are those aged 65, 70, 75, 80, 85, 90, 95 and ≥100. While from the 2nd year to the 5th year, those who will age 65, 70, 75, 80, 85, 90, 95 and 100 will receive the same subsidised shot. Methods We performed economic evaluations to (1) evaluate the efficiency of alternative strategies of PPSV–23 single-dose immunisation programme, and (2) investigate the efficiency of PCV–13 inclusion in the list for single-dose pneumococcal vaccine immunisation programme. Three alternative strategies were created in this study, namely: (1) current PPSV–23 strategy, (2) 65 to 80 (as “65–80 PPSV–23 strategy”), and (3) 65 and older (as “≥65 PPSV–23 strategy”). We constructed a Markov model depicting the S. pneumoniae-related disease course pathways. The transition probabilities, utility weights to estimate quality adjusted life year (QALY) and disease treatment costs were either calculated or cited from literature. Cost of per shot of vaccine was ¥8,116 (US$74; US$1 = ¥110) for PPSV–23 and ¥10,776 (US$98) for PCV–13. The model runs for 15 years with one year cycle after immunisation. Discounting was at 3%. Results Compared to current PPSV–23 strategy, 65–80 PPSV–23 strategy cost less but gained less, while the incremental cost-effectiveness ratios (ICERs) of ≥65 PPSV–23 strategy was ¥5,025,000 (US$45

  5. Orbital complications of acute sinusitis: changes in the post-pneumococcal vaccine era.

    Science.gov (United States)

    Peña, Maria T; Preciado, Diego; Orestes, Michael; Choi, Sukgi

    2013-03-01

    The widespread use of the 7-valent pneumococcal conjugate vaccine (PVC7), developed to combat invasive Streptococcus pneumoniae infections, has the potential to influence the prevalence and antibiotic resistance patterns of pathogens associated with orbital complications from acute sinusitis. Given the significant morbidity that may result from inadequate treatment of orbital infections related to acute sinusitis, determining the impact of PCV7 on the bacteriology and drug resistance of the pathogens associated with these infections may provide critical information needed to accurately guide optimal clinical management. To determine if the characteristics of orbital complications from acute sinusitis in children have changed in the post-PCV7 era. Review of clinical data. Tertiary care children's hospital. Patients with a diagnosis of orbital cellulitis and/or subperiosteal abscess from January 1, 1996, to December 31, 2009. Patients with immune deficiency or orbital trauma were excluded. Patients were divided into pre-PCV7 (before 2003 [n = 128]) and post-PCV7 (2003 and after [n = 145]) groups. Statistical analyses were used to compare the 2 groups. Differences in patient demographics, signs and symptoms, laboratory study results, computed tomography scan findings, and microbiological analyses between the pre-PCV7 and post-PCV7 groups. A total of 273 children met the inclusion criteria. The post-PCV7 group was older (71.4 months vs 88.8 months [P = .007]) than the pre-PCV7 group. A significant decrease in S pneumoniae and Streptococcus viridans -positive sinus or blood cultures were observed (22.4% vs 0% [P sinusitis complications in this series, there has been a parallel and significant increase in S aureus, including an increase in the prevalence of MRSA associated with orbital infections related to acute sinusitis.

  6. [Surveillance of Haemophilus influenzae serotypes in Argentina from 2005 to 2010 during the Haemophilus influenzae type b conjugate vaccine era].

    Science.gov (United States)

    Efron, Adriana M; Moscoloni, María A; Reijtman, Vanesa R; Regueira, Mabel

    2013-01-01

    The introduction of the Haemophilus influenzae type b vaccine in the immunization programs of many countries has greatly reduced this invasive disease and the carriage caused by this serotype, also increasing other capsular types and non-capsular isolations. There were 313 isolations of H. influenzae under study, which were recovered from a sterile site coming from pediatric and adult patients carrying the invasive disease. Patients were treated at 90 different hospitals belonging to the Red Nacional de Laboratorios para Meningitis e Infecciones Respiratorias Agudas Bacterianas (National Lab Network for Meningitis and Acute Bacterial Respiratory Infections) from 2005 to 2010 for the following disorders: pneumonia, 40.3% (n=126), meningitis, 30.0% (n=94) and bacteremia, 26.5% (n=83). In pediatric patients (n=279), the highest frequency of isolations corresponded to children under the age of 2 years, 74.5% (n=208). Regarding type distribution, 61.3% corresponded to non-capsular H. influenzae (n=192), 20.1% to type b (n=63), 11.2% to type a (n=35), 4.8% to type f, and 2.6% to other types. Capsular H. influenzae was predominant in meningitis whereas non-capsular H. influenzae in pneumonia and bacteremia. The biotype was determined in 306 isolations. The totality (100%) of type a (n=35) was biotype II whereas 66.7% of type b (n=63) was biotype I. Slide agglutination and PCR tests were used in 220 isolations. There was a match of 0.982 (IC: 0.92-1.00) between them. During the last year, there was a great increase in type b, showing the importance of clinical and laboratory-based surveillance of the invasive disease caused by H. influenzae.

  7. Evaluation of the induction of immune memory following infant immunisation with serogroup C Neisseria meningitidis conjugate vaccines--exploratory analyses within a randomised controlled trial.

    Science.gov (United States)

    Khatami, Ameneh; Clutterbuck, Elizabeth A; Thompson, Amber J; McKenna, Jennifer A; Pace, David; Birks, Jacqueline; Snape, Matthew D; Pollard, Andrew J

    2014-01-01

    We measured meningococcal serogroup C (MenC)-specific memory B-cell responses in infants by Enzyme-Linked Immunospot (ELISpot) following different MenC conjugate vaccine schedules to investigate the impact of priming on immune memory. Infants aged 2 months were randomised to receive 1 or 2 doses of MenC-CRM197 at 3 or 3 and 4 months, 1 dose of MenC-TT at 3 months, or no primary MenC doses. All children received a Haemophilus influenzae type b (Hib)-MenC booster at 12 months. Blood was drawn at 5, 12, 12 months +6 days and 13 months of age. Results were available for 110, 103, 76 and 44 children from each group respectively. Following primary immunisations, and prior to the 12-month booster, there were no significant differences between 1- or 2-dose primed children in the number of MenC memory B-cells detected. One month following the booster, children primed with 1 dose MenC-TT had more memory B-cells than children primed with either 1-dose (p = 0.001) or 2-dose (pmemory B-cells detected in children who received 1 or 2 doses of MenC-CRM197 in infancy and un-primed children. MenC-specific memory B-cell production may be more dependent on the type of primary vaccine used than the number of doses administered. Although the mechanistic differences between MenC-CRM197 and MenC-TT priming are unclear, it is possible that structural differences, including the carrier proteins, may underlie differential interactions with B- and T-cell populations, and thus different effects on various memory B-cell subsets. A MenC-TT/Hib-MenC-TT combination for priming/boosting may offer an advantage in inducing more persistent antibody. EU Clinical Trials Register 2009-016579-31 ClinicalTrials.gov NCT01129518.

  8. Reemplazo de serotipos de Streptococcus pneumoniae en niños con vacuna conjugada antineumocóccica 7V en México Streptococcus pneumoniae serotype replacement in nasopharyngeal colonization in children vaccinated with PCV7 in Mexico

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    Luz Elena Espinosa-de los Monteros

    2010-02-01

    Full Text Available OBJETIVO: Evaluar el efecto de la inmunización con vacuna neumocóccica conjugada 7 valente (VCN7, sobre la colonización nasofaríngea por S. pneumoniae (SPN. MATERIAL Y MÉTODOS: Se estudiaron dos grupos con diferente esquema de vacunación: grupo I (2-6 meses de edad 3+1, grupo II (7-11 meses 2+1, con refuerzo a los 15 meses de edad. Se realizaron cultivos nasofaríngeos antes de cada inmunización y posterior al refuerzo; se analizó de forma global y pareada las proporciones de los niños colonizados por SPN, serotipos vacunales, no vacunales y resistencia a la penicilina. RESULTADOS: Se incluyeron 183 niños; 93 en el grupo I y 90 en el grupo II. En el grupo I disminuyeron los serotipos vacunales en la 3ª muestra. En el grupo II aumentaron los serotipos no vacunales y disminuyeron los serotipos vacunales antes del refuerzo. En ambos grupos hay una tendencia a disminuir la resistencia a penicilina. CONCLUSIÓN: La VCN7 ocasiona un reemplazo de serotipos en la colonización nasofaríngea antes del refuerzo.OBJECTIVE: To assess the impact of pneumococcal conjugate vaccine (PCV7 immunization on pneumococcal nasopharyngeal colonization with S. pneumoniae (SPN. MATERIAL AND METHODS: We studied two groups with different vaccination schedules, group I (2-6 months of age 3+1 and group II (7 -11 months 2+1, with a booster at 15 months. Nasopharyngeal cultures were obtained before administering each vaccination dose and after booster. Paired and global analyses were carried out of the proportions of children colonized by SPN, vaccine serotype, no vaccine serotype and resistance to penicillin. RESULTS: A total of 183 children were enrolled; 93 in group I and 90 in group II. In group I, there was a decrease in vaccine serotypes in the third sample. In group II, there was an increase in non-vaccine serotypes and a decrease in vaccine serotypes before booster. Both groups showed a trend toward decreased resistance to penicillin. CONCLUSION: PCV7 caused

  9. 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

  10. A Cholera Conjugate Vaccine Containing O-specific Polysaccharide (OSP of V. cholerae O1 Inaba and Recombinant Fragment of Tetanus Toxin Heavy Chain (OSP:rTTHc Induces Serum, Memory and Lamina Proprial Responses against OSP and Is Protective in Mice.

    Directory of Open Access Journals (Sweden)

    Md Abu Sayeed

    Full Text Available Vibrio cholerae is the cause of cholera, a severe watery diarrhea. Protection against cholera is serogroup specific. Serogroup specificity is defined by the O-specific polysaccharide (OSP component of lipopolysaccharide (LPS.Here we describe a conjugate vaccine for cholera prepared via squaric acid chemistry from the OSP of V. cholerae O1 Inaba strain PIC018 and a recombinant heavy chain fragment of tetanus toxin (OSP:rTTHc. We assessed a range of vaccine doses based on the OSP content of the vaccine (10-50 μg, vaccine compositions varying by molar loading ratio of OSP to rTTHc (3:1, 5:1, 10:1, effect of an adjuvant, and route of immunization.Immunized mice developed prominent anti-OSP and anti-TT serum IgG responses, as well as vibriocidal antibody and memory B cell responses following intramuscular or intradermal vaccination. Mice did not develop anti-squarate responses. Intestinal lamina proprial IgA responses targeting OSP occurred following intradermal vaccination. In general, we found comparable immune responses in mice immunized with these variations, although memory B cell and vibriocidal responses were blunted in mice receiving the highest dose of vaccine (50 μg. We found no appreciable change in immune responses when the conjugate vaccine was administered in the presence or absence of immunoadjuvant alum. Administration of OSP:rTTHc resulted in 55% protective efficacy in a mouse survival cholera challenge model.We report development of an Inaba OSP:rTTHc conjugate vaccine that induces memory responses and protection against cholera in mice. Development of an effective cholera conjugate vaccine that induces high level and long-term immune responses against OSP would be beneficial, especially in young children who respond poorly to polysaccharide antigens.

  11. A Cholera Conjugate Vaccine Containing O-specific Polysaccharide (OSP) of V. cholerae O1 Inaba and Recombinant Fragment of Tetanus Toxin Heavy Chain (OSP:rTTHc) Induces Serum, Memory and Lamina Proprial Responses against OSP and Is Protective in Mice

    Science.gov (United States)

    Eckhoff, Grace; Charles, Richelle C.; Alam, Mohammad Murshid; Sultana, Tania; Rashu, Md. Rasheduzzaman; Berger, Amanda; Gonzalez-Escobedo, Geoffrey; Mandlik, Anjali; Bhuiyan, Taufiqur Rahman; Leung, Daniel T.; LaRocque, Regina C.; Harris, Jason B.; Calderwood, Stephen B.; Qadri, Firdausi; Vann, W. F.; Kováč, Pavol; Ryan, Edward T.

    2015-01-01

    Background Vibrio cholerae is the cause of cholera, a severe watery diarrhea. Protection against cholera is serogroup specific. Serogroup specificity is defined by the O-specific polysaccharide (OSP) component of lipopolysaccharide (LPS). Methodology Here we describe a conjugate vaccine for cholera prepared via squaric acid chemistry from the OSP of V. cholerae O1 Inaba strain PIC018 and a recombinant heavy chain fragment of tetanus toxin (OSP:rTTHc). We assessed a range of vaccine doses based on the OSP content of the vaccine (10-50 μg), vaccine compositions varying by molar loading ratio of OSP to rTTHc (3:1, 5:1, 10:1), effect of an adjuvant, and route of immunization. Principle Findings Immunized mice developed prominent anti-OSP and anti-TT serum IgG responses, as well as vibriocidal antibody and memory B cell responses following intramuscular or intradermal vaccination. Mice did not develop anti-squarate responses. Intestinal lamina proprial IgA responses targeting OSP occurred following intradermal vaccination. In general, we found comparable immune responses in mice immunized with these variations, although memory B cell and vibriocidal responses were blunted in mice receiving the highest dose of vaccine (50 μg). We found no appreciable change in immune responses when the conjugate vaccine was administered in the presence or absence of immunoadjuvant alum. Administration of OSP:rTTHc resulted in 55% protective efficacy in a mouse survival cholera challenge model. Conclusion We report development of an Inaba OSP:rTTHc conjugate vaccine that induces memory responses and protection against cholera in mice. Development of an effective cholera conjugate vaccine that induces high level and long-term immune responses against OSP would be beneficial, especially in young children who respond poorly to polysaccharide antigens. PMID:26154421

  12. Carrier priming effect of CRM197 is related to an enhanced B and T cell activation in meningococcal serogroup A conjugate vaccination. Immunological comparison between CRM197 and diphtheria toxoid.

    Science.gov (United States)

    Pecetta, S; Tontini, M; Faenzi, E; Cioncada, R; Proietti, D; Seubert, A; Nuti, S; Berti, F; Romano, M R

    2016-04-29

    Glycoconjugate vaccines are composed of capsular polysaccharides (CPSs) of a pathogenic bacteria covalently linked to carrier proteins. Pre-exposure to the carrier is known to influence the efficacy of the glycoconjugate, by inducing enhanced or suppressed anti-CPS response. Following our previous work on the immunogenicity of diphtheria toxin mutant CRM197 and formaldehyde-treated diphtheria toxoid (DT) as carriers for meningococcal A (MenA) conjugates in mouse model, we further investigated the role of the carrier on the immunological response to glycoconjugate vaccines. We previously showed that high dosage DT priming could result in carrier-induced epitopic suppression (CIES), an event that did not occur for CRM197 priming, and we observed that anti-DT IgGs could cross-react with DT based conjugates in vitro. Here, we confirmed the cross-reactivity of anti-carrier IgGs with DT conjugates in vivo. Furthermore, we analyzed the splenocytes of animals primed with the carrier and subsequently immunized with the MenA conjugate. Pre-exposure to the carrier protein, both CRM197 and DT, resulted in increased carrier-specific plasma and memory B cell response. However, only for CRM197 priming an enhanced carbohydrate-specific plasma cell response was observed. Analysis of circulating IgGs confirmed these observations. Memory to the CPS resulted to be non-influenced by carrier priming. Analysis of T helper response showed an enhancement effect for CRM197 priming, while DT priming resulted in constrained T cell activation. Stimulation with CRM197, which does not require formaldehyde detoxification, of splenocytes from animal immunized with DT suggested that the formaldehyde treatment used to produce DT might be the cause of limited presentation of the antigen to the T cells. We concluded that the dominant carrier-specific B cell response in case of limited T cell recruitment might explain the previously observed CIES phenomenon in case of DT priming.

  13. Immunology Update: New Vaccines.

    Science.gov (United States)

    Starr, S Paul

    2016-11-01

    A new 9-valent human papillomavirus (HPV) vaccine is effective against more cancer-causing HPV types than previous vaccines. HPV vaccine series started with previous vaccines can be completed with the 9-valent vaccine. Two new influenza vaccines are available for adults 65 years and older: a high-dose vaccine and an enhanced adjuvant vaccine. These elicit stronger antibody responses than standard-dose vaccines. Current guidelines specify no preference for the new versus standard-dose vaccines. Two new group B meningococcal vaccines are intended for use during outbreaks and for patients with asplenia, complement deficiencies, frequent occupational meningococcus exposure, or for patients who desire protection from type B meningococcus. These are not substitutes for the quadrivalent vaccine already in use. For pneumococcus, new recommendations state that 13-valent pneumococcal conjugate vaccine (PCV13) should be administered to patients 65 years and older, followed at least 1 year later by the polyvalent pneumococcal polysaccharide vaccine (PPSV23). For patients ages 19 to 64 years with immunocompromise and not previously vaccinated against pneumococcus, administration of these two vaccines should be separated by at least 8 weeks. Rotavirus vaccine is standard for infants at age 2 months. Also, there is a new cholera vaccine approved for use in the United States. Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.

  14. Impact of the introduction of pneumococcal conjugate vaccination on pneumonia in The Gambia: population-based surveillance and case-control studies.

    Science.gov (United States)

    Mackenzie, Grant A; Hill, Philip C; Sahito, Shah M; Jeffries, David J; Hossain, Ilias; Bottomley, Christian; Uchendu, Uchendu; Ameh, David; Ndiaye, Malick; Osuorah, Chidebereh D; Adeyemi, Oyedeji; Pathirana, Jayani; Olatunji, Yekini; Abatan, Bade; Ahameefula, Ebirim; Muhammad, Bilquees S; Fombah, Augustin E; Saha, Debasish; Mackenzie, Roslyn; Plumb, Ian; Akano, Aliu; Ebruke, Bernard; Ideh, Readon C; Kuti, Bankole; Githua, Peter; Olutunde, Emmanuel; Ofordile, Ogochukwu; Green, Edward; Usuf, Effua; Badji, Henry; Ikumapayi, Usman N A; Manjang, Ahmad; Salaudeen, Rasheed; Nsekpong, E David; Jarju, Sheikh; Antonio, Martin; Sambou, Sana; Ceesay, Lamin; Lowe-Jallow, Yamundow; Sowe, Dawda; Jasseh, Momodou; Mulholland, Kim; Knoll, Maria; Levine, Orin S; Howie, Stephen R; Adegbola, Richard A; Greenwood, Brian M; Corrah, Tumani

    2017-09-01

    Pneumococcal conjugate vaccines (PCVs) are used in many low-income countries but their impact on the incidence of pneumonia is unclear. The Gambia introduced PCV7 in August, 2009, and PCV13 in May, 2011. We aimed to measure the impact of the introduction of these vaccines on pneumonia incidence. We did population-based surveillance and case-control studies. The primary endpoint was WHO-defined radiological pneumonia with pulmonary consolidation. Population-based surveillance was for suspected pneumonia in children aged 2-59 months (minimum age 3 months in the case-control study) between May 12, 2008, and Dec 31, 2015. Surveillance for the impact study was limited to the Basse Health and Demographic Surveillance System (BHDSS), whereas surveillance for the case-control study included both the BHDSS and Fuladu West Health and Demographic Surveillance System. Nurses screened all outpatients and inpatients at all health facilities in the surveillance area using standardised criteria for referral to clinicians in Basse and Bansang. These clinicians recorded clinical findings and applied standardised criteria to identify patients with suspected pneumonia. We compared the incidence of pneumonia during the baseline period (May 12, 2008, to May 11, 2010) and the PCV13 period (Jan 1, 2014, to Dec 31, 2015). We also investigated the effectiveness of PCV13 using case-control methods between Sept 12, 2011, and Sept 31, 2014. Controls were aged 90 days or older, and were eligible to have received at least one dose of PCV13; cases had the same eligibility criteria with the addition of having WHO-defined radiological pneumonia. We investigated 18 833 children with clinical pneumonia and identified 2156 cases of radiological pneumonia. Among children aged 2-11 months, the incidence of radiological pneumonia fell from 21·0 cases per 1000 person-years in the baseline period to 16·2 cases per 1000 person-years (23% decline, 95% CI 7-36) in 2014-15. In the 12-23 month age group

  15. Necrotizing pneumonia and acute purulent pericarditis caused by Streptococcus pneumoniae serotype 19A in a healthy 4-year-old girl after one catch-up dose of 13-valent pneumococcal conjugate vaccine.

    Science.gov (United States)

    Lu, Shay; Tsai, Jeng-Dau; Tsao, Ten-Fu; Liao, Pei-Fen; Sheu, Ji-Nan

    2016-08-01

    Streptococcus pneumoniae is a common cause of infectious diseases in children that may lead to life-threatening complications. Acute purulent pericarditis is an uncommon complication of S. pneumoniae in the antibiotic era. A healthy 4-year-old girl was admitted with pneumonia and pleural effusion. She had received one catch-up dose of 13-valent pneumococcal conjugate vaccine at 2 years of age. She rapidly developed necrotizing pneumonia, complicated by bronchopleural fistula presenting as subcutaneous emphysema and pneumothorax and acute purulent pericarditis. S. pneumoniae serotype 19A was subsequently identified from blood, empyema and pericardial fluid cultures. After appropriate antibiotic therapy and a right lower lobectomy, her condition stabilized and she promptly recovered. This case highlights two rare potential clinical complications of pneumococcal disease in a child: necrotizing pneumonia and acute purulent pericarditis. This is the first report of a child who received just one catch-up dose of 13-valent pneumococcal conjugate vaccine at 2 years of age, as per the United States' Advisory Committee on Immunization Practice's recommendations, but who still developed severe invasive pneumococcal disease with life-threatening complications caused by S. pneumoniae serotype 19A.

  16. Heavy-chain isotype patterns of human antibody-secreting cells induced by Haemophilus influenzae type b conjugate vaccines in relation to age and preimmunity

    DEFF Research Database (Denmark)

    Barington, T; Juul, Lars; Gyhrs, A;

    1994-01-01

    The influence of preexisting immunity on the heavy-chain isotypes of circulating antibody-secreting cells (AbSC) induced by vaccination with Haemophilus influenzae type b (Hib) capsular polysaccharide (HibCP) coupled to tetanus toxoid (TT) or diphtheria toxoid (DT) and by vaccination with TT or DT...

  17. 冻干b型流感嗜血杆菌结合疫苗稳定性研究%Study on stability of a freeze-dried Haemophilus influenzae type b conjugate vaccine

    Institute of Scientific and Technical Information of China (English)

    袁军; 李新国

    2011-01-01

    目的 对以乳糖作为稳定剂的b型流感嗜血杆菌(Haemophilus influenzae type b,Hib)结合疫苗冻干剂型进行稳定性研究.方法 选取3批冻干Hib结合疫苗,分别于2~8℃保存42个月,20~25℃保存7个月,37℃保存5周.并于考察期内对疫苗进行外观检查、检测回收率(KD <0.2)、游离多糖含量、水分和小鼠效力试验,观察其是否发生降解.结果 在考察期内,冻干疫苗小鼠效力试验阳转率均为100%,外观检查均符合规定,回收率(KD<0.2)均≥68%,游离多糖均≤18%,水分均≤3.0%.各项指标均达到中国药典要求.结论 冻干疫苗于2~8℃保存42个月,20~25℃保存7个月,37℃保存5周质量稳定.%Objective To research the stability of a freeze-dried Haemophilus influenzae type b (Hib)conjugate vaccine using lactose as a stabilizer.Methods Three batches of the freeze-dried Hib conjugate vaccine were selected to be stored at 2-8 ℃ for 42 months,20-25 ℃ for 7 months and 37 ℃ for 5 weeks,respectively.Tests for appearance,recovery rate of polysaccharide (KD < 0.2),free polysaccharide content,moisture content and mouse potency test were performed during observation to see whether degradation of the vaccine occurred.Results The seroconversion rate in mouse potency test was 100%,the appearance of vaccine was fit for the standard,recovery rate of polysaccharide (KD <0.2) was≥68%,free polysaccharide content≤ 18%,moisture content ≤3.0% for all three batches of the freeze-dried vaccine during observation.All the indexes of freeze-dried vaccine reach the requirements of Chinese Pharmacopeia.Conclusion The freeze-dried Hib conjugate vaccine has stable quality when stored at 2-8℃ for 42 months,20-25℃ for 7 months and 37℃ for 5 weeks.

  18. Safety, reactogenicity and immunogenicity of 2-dose catch-up vaccination with 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in Malian children in the second year of life: Results from an open study.

    Science.gov (United States)

    Dicko, Alassane; Dicko, Yahia; Barry, Amadou; Sidibe, Youssoufa; Mahamar, Almahamoudou; Santara, Gaoussou; Dolo, Amagana; Diallo, Aminata; Doumbo, Ogobara; Shafi, Fakrudeen; François, Nancy; Yarzabal, Juan Pablo; Strezova, Ana; Borys, Dorota; Schuerman, Lode

    2015-01-01

    Pneumonia is still the leading cause of death among African children with pneumococcal serotypes 1 and 5 being dominant in the below 5 y of age group. The present study assessed the safety, reactogenicity and immunogenicity of a 2-dose catch-up vaccination with the 10-valent pneumococcal non-typeable Haemophilus influenzae Protein D conjugate vaccine (PHiD-CV) in Malian children. This phase III, open-label study (NCT00985465) was conducted in Ouelessebougou, Mali, between November 2009 and July 2010. The study population consisted of PHiD-CV unprimed Malian children previously enrolled in the control group of study NCT00678301 receiving a 2-dose catch-up vaccination with PHiD-CV in the second year of life. Adverse events were recorded following each PHiD-CV dose. Antibody responses and opsonophagocytic activity (OPA) were measured pre-vaccination and after the second PHiD-CV catch-up dose. Swelling and fever (axillary temperature ≥ 37.5°C) were the most frequently reported solicited symptoms following either PHiD-CV dose. Few grade 3 solicited symptoms were reported. Large swelling reactions and serious adverse events were not reported. Post-catch-up vaccination, for each vaccine pneumococcal serotype, at least 94.7% of subjects had antibody concentrations ≥ 0.2 μg/ml, except for serotypes 6B (82.5%) and 23F (87.7%). At least 94.0% of subjects had OPA titres ≥ 8, except for serotype 19F (89.4%). The geometric mean concentration for antibodies against protein D was 839.3 (95% CI: 643.5-1094.6) EL.U/ml. Two-dose PHiD-CV catch-up regimen in the second year of life was well-tolerated and immunogenic for all vaccine pneumococcal serotypes and NTHi protein D when administered to Malian children.

  19. An investigational tetravalent meningococcal serogroups A, C, W-135 and Y-tetanus toxoid conjugate vaccine co-administered with Infanrix™ hexa is immunogenic, with an acceptable safety profile in 12-23-month-old children.

    Science.gov (United States)

    Knuf, Markus; Pantazi-Chatzikonstantinou, Anna; Pfletschinger, Ulrich; Tichmann-Schumann, Irmingard; Maurer, Hartwig; Maurer, Lothar; Fischbach, Thomas; Zinke, Henrike; Pankow-Culot, Heidemarie; Papaevangelou, Vassiliki; Bianco, Veronique; Van der Wielen, Marie; Miller, Jacqueline M

    2011-06-06

    Tetravalent meningococcal serogroups ACWY conjugate vaccines will provide an advantage to those at most risk of invasive meningococcal disease; namely young children. Co-administration of ACWY-TT with DTaP-HBV-IPV/Hib was assessed in a randomized trial in 793 children aged 12-23 months. Pre-specified criteria for non-inferiority of immunogenicity following co-administration versus separate ACWY-TT and DTaP-HBV-IPV/Hib administration were reached. One month post-vaccination, ≥ 97.3% of ACWY-TT vaccinees had rSBA titres ≥ 1:8 (all serogroups). Seroprotection/seropositivity rates against DTaP-HBV-IPV/Hib antigens were ≥ 98.2%. The safety profile of co-administration was similar to that of DTaP-HBV-IPV/Hib alone. ACWY-TT and DTaP-HBV-IPV/Hib co-administration during the second year would facilitate introduction of ACWY-TT into routine toddler vaccination schedules.

  20. Preparation and immunogenicity-evaluation of typhoid O-specific polysaccharides bio-conjugate vaccines%生物法合成伤寒O-糖蛋白结合疫苗及其免疫原性评估

    Institute of Scientific and Technical Information of China (English)

    彭哲慧; 潘超; 孙鹏; 冯尔玲; 吴军; 朱力; 彭清忠; 王恒樑

    2015-01-01

    Typhoid fever caused bySalmonella Typhi is still a major public health problem in developing coun-tries. In this study, we constructed a genetically modifiedSalmonella Typhi strain expressing O-specific polysaccha-rides (OPS) antigen conjugated to a carrier, recombinant Pseudomonas aeruginosa exotoxin A(rEPA N29). The conju-gates (OPS-rEPA N29) were further purified and evaluated for their immunogenicity. The results of ELISA showed that the conjugates evoked higher titers of IgG than OPS, suggesting that rEPAN29 increased immunogenicity of OPS significantly as a carrier. Moreover, three injections with 3-week interval evoked slightly higher titers of IgG than three injections with 2-week interval. However, injection of excess conjugates could not evoke higher titers of IgG against lipid polysaccharide (LPS). In summary, our study provides a new strategy for preparing polysaccha-rides-protein conjugate vaccines as well as similar bio-conjugate vaccines of other Gram-negative pathogens.%伤寒由伤寒沙门氏菌(Salmonella Typhi)引发,至今在发展中国家仍是备受关注的重要公共卫生问题.文章通过敲除伤寒菌脂多糖合成途径中O-抗原连接酶基因,转入含脑膜炎奈瑟球菌(Neisseria meningitidis)蛋白糖基化途径中糖基转移酶的表达载体,以及改构的重组铜绿假单胞菌(Pseudomonas Aeruginosa)外毒素A(rEPAN29)的表达载体,使细胞内能够诱导合成以伤寒O特异性多糖(O-specific polysaccharides, OPS)为目标抗原、以rEPAN29为载体蛋白的伤寒OPS-rEPAN29糖蛋白复合物,并对纯化所得复合物进行了免疫原性评价.ELISA测定血清抗体滴度表明,rEPA N29作为载体蛋白能有效增加糖链的免疫原性,糖蛋白比单独的多糖能诱导产生更好的免疫应答;3次免疫、间隔3周比间隔2周IgG滴度稍有提高;而免疫过量的糖蛋白,抗O-多糖的血清抗体效价并无提升.文章为生物法制备多糖-蛋白结合疫苗提供了新思路,理论

  1. The immunogenicity and safety of an investigational meningococcal serogroups A, C, W-135 and Y tetanus toxoid conjugate vaccine (ACWY-TT) compared with a licensed meningococcal tetravalent polysaccharide vaccine

    OpenAIRE

    Dbaibo, Ghassan; Macalalad, Noel; Reyes, Mari Rose Aplasca-De Los; Dimaano, Efren; Bianco, Véronique; Baine, Yaela; Miller, Jacqueline

    2012-01-01

    Immunogenicity and safety of ACWY-TT compared with licensed ACWY polysaccharide vaccine (MenPS) in healthy adults, and lot-to-lot consistency of three ACWY-TT lots were evaluated in a phase 3, open, controlled study. Adults aged 18–55 y were randomized to receive ACWY-TT (one of three lots) or MenPS. Serum bactericidal antibodies (rSBA) were measured pre- and 1 mo post-vaccination. Adverse events (AEs) were assessed 4 d (solicited symptoms) and 31 d (unsolicited symptoms) post-vaccination. Se...

  2. Immunogenicity and safety of a pentavalent acellular pertussis combined vaccine including diphtheria, tetanus, inactivated poliovirus and conjugated Haemophilus Influenzae type b polysaccharide for primary vaccination at 2, 3, 4 or 3, 4, 5 months of age in infants in China.

    Science.gov (United States)

    Li, Rong Cheng; Li, Feng Xiang; Li, Yan Ping; Hou, Qi Ming; Li, Chang Gui; Li, Ya Nan; Chen, Fu Sheng; Hu, Xue Zhong; Su, Wen Bin; Zhang, Shu Min; Fang, Han Hua; Ye, Qiang; Zeng, Tian De; Liu, Tao Xuan; Li, Xiu Bi; Huang, Yun Neng; Deng, Man Ling; Zhang, Yan Ping; Ortiz, Esteban

    2011-02-24

    The aim was to demonstrate the immunogenicity and safety of a DTaP-IPV//PRP-T combined vaccine (Pentaxim(®)) compared to individual vaccines in infants in the People's Republic of China. Infants (N=792) were randomly assigned to receive DTaP-IPV//PRP-T at 2, 3 and 4 months of age (Group A) or 3, 4 and 5 months of age (Group B), or DTaP (Wuhan Institute of Biological Products), PRP-T (Act-Hib(®)) and IPV (Imovax(®) Polio) at 3, 4 and 5 months of age (Group C). Antibody titers were measured pre- and 1 month after the third vaccination; non-inferiority analyses were performed for seroprotection/seroconversion (SP/SC) rates. Safety was assessed 1 month after the primary series. SP/SC rates for the DTaP-IPV//PRP-T vaccine were high and non-inferior to the controls. Reactogenicity was low for each group and no hypotonic hyporesponsive episode or seizure was reported. In conclusion, the DTaP-IPV//PRP-T vaccine was highly immunogenic, non-inferior to the commercially available control vaccines and had a good safety profile for both primary administration schedules.

  3. Use of 23-valent pneumococcal polysaccharide vaccine and 13-valent pneumococcal conjugate vaccine among adults%23价肺炎链球菌多糖疫苗和13价肺炎链球菌结合疫苗在成年人中的应用

    Institute of Scientific and Technical Information of China (English)

    朱朗; 陈磊; 林纪胜; 高强; 王见冬; 王新立; 蔡芳

    2015-01-01

    Streptococcus pneumoniae is an important pathogen causing serious diseases such as pneumonia, septicemia and meningitis in people of all ages, especially in young children and the eldly worldwide.These diseases can be prevented by pneumococcal vaccines.In countries where pneumococcal vaccines have been introduced in national immunization program, the incidence of pneumococcal diseases and the carriage of pneumococcal vaccine serotypes decreased dramatically in children, and indirect herd protection was developed among unvaccinated people.The utilization of 23-valent pneumococcal polysaccharide vaccine and 13-valent pneumococcal conjugate vaccine are discussed in this article.%肺炎链球菌是引起全球不同年龄人群,尤其是幼儿和老年人肺炎、败血症和脑膜炎等严重疾病的重要病原菌,由肺炎链球菌导致的这些疾病可以通过疫苗进行预防.在将肺炎链球菌疫苗纳入国家免疫计划的国家,儿童肺炎链球菌病的发病率以及疫苗型肺炎链球菌的携带率大大降低,且可在未免疫人群中产生间接保护作用.此文对23价肺炎链球菌多糖疫苗和1 3价肺炎链球菌结合疫苗在成年人中的应用进行探讨.

  4. Typhoid fever vaccination strategies.

    Science.gov (United States)

    Date, Kashmira A; Bentsi-Enchill, Adwoa; Marks, Florian; Fox, Kimberley

    2015-06-19

    Typhoid vaccination is an important component of typhoid fever prevention and control, and is recommended for public health programmatic use in both endemic and outbreak settings. We reviewed experiences with various vaccination strategies using the currently available typhoid vaccines (injectable Vi polysaccharide vaccine [ViPS], oral Ty21a vaccine, and injectable typhoid conjugate vaccine [TCV]). We assessed the rationale, acceptability, effectiveness, impact and implementation lessons of these strategies to inform effective typhoid vaccination strategies for the future. Vaccination strategies were categorized by vaccine disease control strategy (preemptive use for endemic disease or to prevent an outbreak, and reactive use for outbreak control) and vaccine delivery strategy (community-based routine, community-based campaign and school-based). Almost all public health typhoid vaccination programs used ViPS vaccine and have been in countries of Asia, with one example in the Pacific and one experience using the Ty21a vaccine in South America. All vaccination strategies were found to be acceptable, feasible and effective in the settings evaluated; evidence of impact, where available, was strongest in endemic settings and in the short- to medium-term. Vaccination was cost-effective in high-incidence but not low-incidence settings. Experience in disaster and outbreak settings remains limited. TCVs have recently become available and none are WHO-prequalified yet; no program experience with TCVs was found in published literature. Despite the demonstrated success of several typhoid vaccination strategies, typhoid vaccines remain underused. Implementation lessons should be applied to design optimal vaccination strategies using TCVs which have several anticipated advantages, such as potential for use in infant immunization programs and longer duration of protection, over the ViPS and Ty21a vaccines for typhoid prevention and control. Copyright © 2015. Published by

  5. Five-year antibody persistence and safety following a booster dose of combined Haemophilus influenzae type b-Neisseria meningitidis serogroup C-tetanus toxoid conjugate vaccine.

    Science.gov (United States)

    Tejedor, Juan Carlos; Merino, José Manuel; Moro, Manuel; Navarro, Maria-Luisa; Espín, José; Omeñaca, Félix; García-Sicilia, José; Moreno-Pérez, David; Ruiz-Contreras, Jesús; Centeno, Fernando; Barrio, Francisco; Cabanillas, Lucia; Muro, Marta; Esporrin, Carlos; De Torres, Maria Jose; Caubet, Magalie; Boutriau, Dominique; Miller, Jacqueline M; Mesaros, Narcisa

    2012-10-01

    Booster vaccination with the combined Haemophilus influenza type b-Neisseria meningitides serogroup C-tetanus toxoid vaccine (Hib-MenC-TT) has been reported to induce different MenC antibody responses depending on the priming vaccines, with a possible impact on long-term protection. Here, the five-year persistence of immune responses induced by a booster dose of Hib-MenC-TT was evaluated in toddlers primed with either Hib-MenC-TT or MenC-TT. This is the follow-up of a phase III, open, randomized study, in which a Hib-MenC-TT booster dose was given at 13.14 months of age to toddlers primed with either 3 doses of Hib-MenC-TT or 2 doses of MenC-TT in infancy. Children in the control group had received 3 primary doses and a booster dose of MenC-CRM197. Functional antibodies against MenC were measured by a serum bactericidal assay with rabbit complement (rSBA-MenC) and antibodies against Hib polyribosylribitol phosphate by enzyme-linked immunosorbent assay. Serious adverse events considered by the investigator to be possibly related to vaccination were to be reported throughout the study. At 66 months postbooster, rSBA-MenC titers ≥8 were retained by 82.6% of children primed with Hib-MenC-TT, 94.1% of children primed with MenC-TT, and 60.9% of children in the control group. All children who received the Hib-MenC-TT booster dose retained anti- polyribosylribitol phosphate concentrations ≥0.15 μg/mL. No serious adverse events considered possibly related to vaccination were reported. There is evidence of good antibody persistence against MenC and Hib for more than five years postbooster vaccination with Hib-MenC TT in toddlers primed with Hib-MenC-TT or MenC-TT.

  6. Oral delivery of probiotic expressing M cell homing peptide conjugated BmpB vaccine encapsulated into alginate/chitosan/alginate microcapsules.

    Science.gov (United States)

    Jiang, Tao; Singh, Bijay; Maharjan, Sushila; Li, Hui-Shan; Kang, Sang-Kee; Bok, Jin-Duck; Cho, Chong-Su; Choi, Yun-Jaie

    2014-11-01

    Oral administration of live probiotics as antigen delivery vectors is a promising approach in vaccine development. However, the low survival of probiotics in the gastrointestinal tract limits this approach. Therefore, the aim of this study was the encapsulation of probiotic expressing vaccine into alginate/chitosan/alginate (ACA) microcapsules (MCs) for efficient oral vaccine delivery. Here, recombinant Lactobacillus plantarum 25 (LP25) expressing M cell homing peptide fused BmpB protein was used as a model probiotic. The viability of LP25 in ACA MCs was more than 65% in simulated gastric fluid (SGF, pH 2.0) and 75% in simulated small intestinal fluid (SIF, pH 7.2) up to 2h. Encapsulated LP25 was completely released from ACA MCs in SIF within 12h. When stored at room temperature (RT) or 4°C, the viability of LP25 in ACA MCs was higher than free LP25. Interestingly, the viability of LP25 in ACA MCs at 4°C for 5weeks was above 58%, whereas viability of free LP25 stored at RT up to 5weeks was zero. After 4weeks from the first immunization, LP25-M-BmpB-loaded ACA MCs induced a stronger BmpB-specific IgG and IgA production in mice. Collectively, these findings suggest that encapsulation of probiotic by ACA MCs is a promising delivery system for oral administration of probiotic expressing vaccine. Copyright © 2014 Elsevier B.V. All rights reserved.

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

    OpenAIRE

    Irma Gabriela Echániz-Avilés; Fortino Solórzano-Santos

    2001-01-01

    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 co...

  8. The efficacy and safety of a nicotine conjugate vaccine (NicVAX® or placebo co-administered with varenicline (Champix® for smoking cessation: study protocol of a phase IIb, double blind, randomized, placebo controlled trial

    Directory of Open Access Journals (Sweden)

    Hoogsteder Philippe HJ

    2012-12-01

    Full Text Available Abstract Background A potential new treatment in smoking cessation and relapse prevention is nicotine vaccination which is based on active immunization against the nicotine molecule. This immunization will elicit the immune system to produce nicotine-specific antibodies that sequester nicotine in the blood stream, after inhaling tobacco products. The resulting antibody-antigen is too large to cross the blood–brain barrier and is therefore postulated to attenuate the rewarding effect of nicotine by preventing the latter from reaching its receptors in the brain and causing the release of dopamine. The aim of this paper is to describe the design of a phase IIb, multi-center, double blind, randomized, placebo controlled trial to assess the efficacy of the nicotine vaccine NicVAX® co-administered with varenicline (Champix® and intensive counseling as an aid in smoking cessation and relapse prevention. Methods/design Two centers will include a total of 600 smokers who are motivated to quit smoking. At week −2 these smokers will be randomized, in a 1:1 ratio, to either 6 injections of NicVAX® or placebo, both co-administered with 12-weeks of varenicline treatment, starting at week 0. The target quit day will be set after 7 days of varenicline treatment at week 1. Smokers will be followed up for 54 weeks. The primary outcome is defined as biochemically validated prolonged smoking abstinence from week 9 to 52. Secondary outcomes include safety, immunogenicity, smoking abstinence from week 37 to 52, abstinence from week 9 to 24, abstinence in the subset of subjects with the highest antibody response, and lapse/relapse rate. Discussion This is the first study to assess the efficacy of a nicotine conjugate vaccine in combination with an evidence-based smoking cessation pharmacotherapy (varenicline to quit smoking. Although NicVAX® is primarily designed as an aid to smoking cessation, our study is designed to explore its potential to maintain

  9. Research of universal influenza virus vaccine conjugated human papillomavirus 16 LI as a vector%以人乳头瘤病毒16 L1为载体的流感通用疫苗初步研究

    Institute of Scientific and Technical Information of China (English)

    刘蕊; 李志奎; 王希良; 罗德炎; 颜艳; 陈中伟; 花艳红

    2008-01-01

    Objective To construct a universal influenza virus vaccine Baemid containing M2 extracellular domain(M2e) of influenza virus which conjugated human papillomavirus(HPV)16 L1 as a vector and expressed the protein in insect baeulovirus system. Methods HPV16 L1 gene was amplified by PCR with the primers contained M2e gene. The conjugated genes were inserted into pFast HTA vector to recombine in DHI0Bac. The recombinant baemid was transfected into sf9 insect cells by liposome to produce baculovirus contained M2e-HPVI6 L1. Protein was determined by SDS-PAGE, immunofluorescence and electronmicroseope. Results The universal influenza virus vaccine Bacmid containing M2e of influenza virus which conjugated HPV16 L1 as a vector was successfully constructed. The recombinant protein wasexpressed in insect cells. Conclusions The recombinant protein was expressed in insect cells in the form of virus-like particles through the baculovirus system,which was a base of the universal influenza virus vaccine development.%目的 构建以人乳头瘤病毒(human papillomavirus,HPV)16 L1为载体的甲型流感病毒M2基因胞外区(M2e)通用疫苗杆粒,利用昆虫细胞杆状病毒表达系统,进行初步的蛋白表达.方法 利用PCR技术将甲型流感病毒M2e基因序列与HPVl6 L1相连.经酶切、酶联将融合基因插入pFastBacHTA载体,在DH10Bac细胞中进行同源重组,经测序鉴定后构建M2e-HPV16 L1杆粒,脂质体转染sf9昆虫细胞,收获并扩增含有M2e-HPV16 L1的杆状病毒,经扩增后获得高效价的重组杆状病毒,用SDS-PAGE、免疫荧光法和电镜检测目的蛋白的表达.结果 构建了以HPV16 L1为载体的M2e通用疫苗杆粒,通过转染sf9昆虫细胞得到初步M2e-HPV16 L1融合蛋白表达.结论 成功构建了HPV16 L1与甲型流感病毒M2e融合蛋白的病毒样颗粒,为流感通用疫苗的研制奠定了基础.

  10. Endogenous IL-1R1 Signaling Is Critical for Cognate CD4+ T Cell Help for Induction of In Vivo Type 1 and Type 2 Antipolysaccharide and Antiprotein Ig Isotype Responses to Intact Streptococcus pneumoniae, but Not to a Soluble Pneumococcal Conjugate Vaccine

    Science.gov (United States)

    2006-08-01

    Isotype Responses to Intact Streptococcus pneumoniae , but Not to a Soluble Pneumococcal Conjugate Vaccine1,2 Quanyi Chen, Goutam Sen, and Clifford M...intact Streptococcus pneumoniae (Pn). Because type 1 IL-1R (IL-1R1) signaling is MyD88 dependent, a role for endogenous IL-1 was determined. IL-1R1... Streptococcus pneumoniae (Pn), a Gram-positive extracellular bacterium, elicits T cell-inde- pendent (TI) IgM responses specific for the

  11. Rapid modification of retroviruses using lipid conjugates

    Science.gov (United States)

    Mukherjee, Nimisha G.; Lyon, L. Andrew; LeDoux, Joseph M.

    2009-02-01

    Methods are needed to manipulate natural nanoparticles. Viruses are particularly interesting because they can act as therapeutic cellular delivery agents. Here we examine a new method for rapidly modifying retroviruses that uses lipid conjugates composed of a lipid anchor (1,2-distearoyl-sn-glycero-3-phosphoethanolamine), a polyethylene glycol chain, and biotin. The conjugates rapidly and stably modified retroviruses and enabled them to bind streptavidin. The implication of this work for modifying viruses for gene therapy and vaccination protocols is discussed.

  12. Systematic review of human papillomavirus vaccine coadministration.

    Science.gov (United States)

    Noronha, Alinea S; Markowitz, Lauri E; Dunne, Eileen F

    2014-05-13

    Human papillomavirus (HPV) vaccination is recommended in early adolescence, at an age when other vaccines are also recommended. Administration of multiple vaccines during one visit is an opportunity to improve uptake of adolescent vaccines. We conducted a systematic review of safety and immunogenicity of HPV vaccines coadministered with other vaccines. Our review included 9 studies, 4 of quadrivalent HPV vaccine and 5 of bivalent HPV vaccine; coadministered vaccines included: meningococcal conjugate, hepatitis A, hepatitis B, combined hepatitis A and B, tetanus, diphtheria, acellular pertussis, and inactivated poliovirus vaccines. Studies varied in methods of data collection and measurement of immunogenicity and safety. Noninferiority of immune response and an acceptable safety profile were demonstrated when HPV vaccine was coadministered with other vaccines.

  13. Impact and Effectiveness of 10 and 13-Valent Pneumococcal Conjugate Vaccines on Hospitalization and Mortality in Children Aged Less than 5 Years in Latin American Countries: A Systematic Review

    Science.gov (United States)

    de Oliveira, Lucia Helena; Camacho, Luiz Antonio B.; Coutinho, Evandro S. F.; Martinez-Silveira, Martha S.; Carvalho, Ana Flavia; Ruiz-Matus, Cuauhtemoc; Toscano, Cristiana M.

    2016-01-01

    Background Several Latin American and Caribbean (LAC) countries have introduced pneumococcal conjugate vaccine (PCV-10 or PCV-13) in their routine national immunization programs. Objectives We aimed to summarize the evidence of PCV impact and effectiveness in children under 5 years old in the LAC Region. Methods We conducted a systematic review of the literature on impact or effectiveness of PCVs on deaths or hospitalizations due to invasive pneumococcal disease (IPD), pneumonia, meningitis and sepsis. We searched Medline, WoS, Lilacs, Scopus, Central and gray literature published in any language from 2009 to January 2016. We included studies addressing the outcomes of interest in children in the target age group, and with the following designs: randomized trials, cohort or case-control, interrupted time series with at least three data points before and after the intervention, and before-after studies. Screening of citations, data extraction, and risk of bias assessment were conducted in duplicate by independent reviewers, according to the study protocol registered on PROSPERO. Descriptive analysis of the effectiveness measurements and sensitivity analysis were conducted. Effectiveness is reported as 1-OR or 1-RR for case control or cohort/clinical trials, and as percent change of disease incidence rates for before-after studies. Results We identified 1,085 citations, 892 from databases and 193 from other sources. Of these, 22 were further analyzed. Studies were from Brazil, Chile, Uruguay, Argentina, Peru and Nicaragua. Effectiveness ranged from 8.8–37.8% for hospitalizations due to X-ray confirmed pneumonia, 7.4–20.6% for clinical pneumonia, and 13.3–87.7% for meningitis hospitalizations, and 56–83.3% for IPD hospitalization, varying by age, outcome definition, type of vaccine and study design. Conclusions Available evidence to date indicates significant impact of both PCV-10 and PCV-13 in the outcomes studied, with no evidence of the superiority of one

  14. Indirect effects by meningococcal vaccines: herd protection versus herd immunity.

    Science.gov (United States)

    Bröker, Michael

    2011-08-01

    The term "herd immunity" for the indirect effect of meningococcal conjugate vaccines is inaccurate. A more appropriate term is "herd protection," because this term correctly describes the public effects imparted by vaccination campaigns against the meningococcus.

  15. Bacterial vaccines and antibiotic resistance

    OpenAIRE

    Henriques-Normark, Birgitta; Normark, Staffan

    2014-01-01

    Spread of antibiotic resistance is mediated by clonal lineages of bacteria that besides being resistant also possess other properties promoting their success. Some vaccines already in use, such as the pneumococcal conjugate vaccines, have had an effect on these successful clones, but at the same time have allowed for the expansion and resistance evolution of previously minor clones not covered by the vaccine. Since resistance frequently is horizontally transferred it will be difficult to gene...

  16. Survey on the Immunization Status of Category B Vaccine among Children Aged 1 to 2 Years in China%中国1~2岁儿童第二类疫苗接种现况调查分析

    Institute of Scientific and Technical Information of China (English)

    郑景山; 曹玲生; 王华庆; 曹雷; 郭世成; 阿克忠; 王雷; 余文周; 袁平; 姜柯羽; 张国民

    2012-01-01

    , haemophilus influenzae type b conjugate vaccine, oral rotavirus attenuated live vaccine, influenza vaccine and 7-valent pneumococcal conjugate vaccine were 46.93%, 45.31%, 23.67%, 17.47and 9.91% respectively ;and the proportion vaccinated by those surrogate national EPI vaccines, such as hepatitis B vaccine, inactivated poliovirus vaccine, acellular pertussis-diphtheria and tetanus combined vaccine, measles-mumps and rubella combined attenuated live vaccine, meningococcal group A & C conjugate vaccine, Japanese encephalitis inactivated vaccine and hepatitis A inactivated vaccine were 0.70%, 0.53%, 7.67%, 2.26%, 5.70%, 2.34%, 11.66% respectively. The rate of children vaccinated by category B vaccines are higher in developed areas of China than the developing areas. For the category B vaccines which needs multiple doses, the completion of whole coverage are low. Conclusion t is necessary to strengthen standardize management for category B vaccine.

  17. Impact of the 13-Valent Pneumococcal Conjugate Vaccine on Clinical and Hypoxemic Childhood Pneumonia over Three Years in Central Malawi: An Observational Study

    Science.gov (United States)

    McCollum, Eric D.; Nambiar, Bejoy; Deula, Rashid; Zadutsa, Beatiwel; Bondo, Austin; King, Carina; Beard, James; Liyaya, Harry; Mankhambo, Limangeni; Lazzerini, Marzia; Makwenda, Charles; Masache, Gibson; Bar-Zeev, Naor; Kazembe, Peter N.; Mwansambo, Charles; Lufesi, Norman; Costello, Anthony; Armstrong, Ben

    2017-01-01

    Background The pneumococcal conjugate vaccine’s (PCV) impact on childhood pneumonia during programmatic conditions in Africa is poorly understood. Following PCV13 introduction in Malawi in November 2011, we evaluated the case burden and rates of childhood pneumonia. Methods and Findings Between January 1, 2012-June 30, 2014 we conducted active pneumonia surveillance in children 75% three-dose PCV13 coverage (post). We also used multivariable time-series regression, adjusting for autocorrelation and exploring seasonal variation and alternative model specifications in sensitivity analyses. The early versus post analysis showed an increase in cases and rates of total, fast breathing, and indrawing pneumonia and a decrease in danger sign and hypoxemic pneumonia, and pneumonia mortality. At 76% three-dose PCV13 coverage, versus 0%, the time-series model showed a non-significant increase in total cases (+47%, 95% CI: -13%, +149%, p = 0.154); fast breathing cases increased 135% (+39%, +297%, p = 0.001), however, hypoxemia fell 47% (-5%, -70%, p = 0.031) and hospital deaths decreased 36% (-1%, -58%, p = 0.047) in children <5 years. We observed a shift towards disease without danger signs, as the proportion of cases with danger signs decreased by 65% (-46%, -77%, p<0.0001). These results were generally robust to plausible alternative model specifications. Conclusions Thirty months after PCV13 introduction in Malawi, the health system burden and rates of the severest forms of childhood pneumonia, including hypoxemia and death, have markedly decreased. PMID:28052071

  18. 不同剂量伤寒Vi 多糖蛋白结合疫苗在小鼠体内诱导的抗体水平分析%Anal ysis of antibody lve el in mou se model induced by diff erent immunization doses of typhoid Vi conjugate vaccine

    Institute of Scientific and Technical Information of China (English)

    刘月萍; 罗树权; 冯宜扬; 冯琪蓉; 金鑫; 周晖国; 周海飞; 谢贵林; 谭小梅

    2015-01-01

    目的:研究伤寒Vi多糖蛋白结合疫苗免疫效果及不同剂量伤寒Vi多糖蛋白结合疫苗在小鼠体内诱导的抗体水平,以确定合适的免疫剂量。方法将150只清洁级NIH雌性小鼠随机分为5组,分别为A组(06.25μg 结合疫苗组)、B组(1.250μg结合疫苗组)、C组(2.500μg结合疫苗组)、D组(2.500μg多糖组)及阴性组(10 mmol/L PBS),每组30只;另领取10只为空白对照(不接种)。 A、B、C、D 组及阴性组小鼠经腹股沟皮下注射,剂量0.1 mL/只,每隔2周免疫1次,共免疫3次,每次免疫后第7天采血。采用ELISA检测小鼠血清抗体效价,同时对不同剂量伤寒Vi多糖蛋白结合疫苗在小鼠体内诱导的抗体效价进行分析比较。结果与D组相比,A 、B、C 三组诱导的抗体水平与之均有统计学意义(P<0.05);A组与B组、A组与C组之间的抗体水平也具有统计学意义(P<0.05),而B组与C组之间的抗体水平无统计学意义(P>0.05)。说明与多糖疫苗相比,伤寒Vi多糖蛋白结合疫苗能够诱导更高的抗体水平,且具有明显的剂次加强效应。同时证明1.250μg的伤寒Vi多糖蛋白结合疫苗可诱导与25.00μg伤寒Vi多糖蛋白结合疫苗相同的抗体水平。结论伤寒Vi多糖蛋白结合疫苗的两种免疫剂量在小鼠体内可诱导相同的抗体水平,在选择接种剂量时,可致免疫应答的无统计学意义的低剂量可能是较为经济和安全的选择。%Objective To study immunological potency of typhoid Vi conjugate vaccine and analyze antibody level in the mouse model induced by different immunization doses of typhoid Vi conjugate vaccine, on which a suitable immunization dose could be set up.Methods A total of 150 NIH female mice ( in clean level) were randomly devided into five groups including--group A (0.625μg conjugate vaccine), group B (1.250μg conjugate vaccine), group C

  19. [Impact of the 13-valent pneumococcal conjugate vaccine on the incidence of consolidated pneumonia in children younger than 5 years old in Pilar, Buenos Aires: A population-based study].

    Science.gov (United States)

    Gentile, Ángela; Bakir, Julia; Bialorus, Laura; Caruso, Laura; Mirra, Diego; Santander, Celina; Terluk, Mabel; Zurdo, Pablo; Gentile, Fernando; Fermndez, María I

    2015-12-01

    In January 2012, Argentina introduced the 13-valent pneumococcal conjugate vaccine (PCV13) in its immunization schedule for children younger than 2 years old. Coverage in Pilar in 2012 reached>90% for the first two doses and 60% for the third dose. To measure the effectiveness of PCV13 to reduce the incidence of consolidated pneumonia (CP)in the two-year period following its introduction in the immunization schedule. Prospective, population-based study conducted in Pilar. All children younger than 5 year sold with clinical signs of pneumonia assisted at the reference hospitals (both inpatients and outpatients) in the first two years since the vaccine introduction (2012-2013) were included. The annual incidence of CP was compared to the 2003-2005 baseline period. Clinical and radiological assessments were done as per the World Health Organization's criteria. Six hundred and sixty-six patients with clinical suspicion of pneumonia were included. CP was diagnosed in 309 patients; 52.1% were girls, 70.2% were younger than 2 years old, and 56.4% had been immunized with the PCV13; 4.5% (14/309) had bacteriological confirmation (S. pneumoniae: 4; N. meningitidis: 4; S. aureus: 2; others: 4). A significant reduction in the incidence of CP (per 100 000 children younger than 5 years old) was observed between the pre- and postimmunization periods, from 750 (204/27209) to 561 (171/30 475) in 2012 and to 453 (138/30 475) in 2013; effectiveness accounted for 25.2% and 39.6%, respectively. Reduction in infants younger than 1 year old: 33.9% in 2012 and 44.6% in 2013; and in children aged 12-23 months old: 57.9% in 2013. No significant differences were observed in the incidence of CP at an older age. Following the introduction of PCV13 in Argentina's immunization schedule, a fast and significant reduction in the incidence of CP was observed, mainly in infants younger than 1 year old in 2012 and in children younger than 2 years old in 2013.

  20. Neisseria meningitidis B vaccines.

    Science.gov (United States)

    Panatto, Donatella; Amicizia, Daniela; Lai, Piero Luigi; Gasparini, Roberto

    2011-09-01

    Invasive infections caused by Neisseria meningitidis are a serious public health problem worldwide and have a heavy economic impact. The incidence of invasive disease due to Neisseria meningitidis is highly variable according to geographical area and serogroup distribution. Since the introduction of vaccination programs with conjugated vaccine C in children and adolescents, most cases of invasive meningococcal disease in developed countries have been caused by meningococcus B. It is important to underline that invasive meningococcal disease will not be controlled until safe and effective vaccines for meningococcal B are available and widely used. The aims of this article are to describe the most recent developments in meningococcal B vaccines and to discuss how these vaccines can contribute to containing meningococcal disease.

  1. Vaccines for preventing typhoid fever (Review)

    OpenAIRE

    Anwar, Elspeth; Goldberg, Elad; Fraser, Abigail; Acosta, Camilo J.; Paul, Mical; Leibovici, Leonard

    2014-01-01

    Background\\ud Typhoid fever and paratyphoid fever continue to be important causes of illness and death, particularly among children and adolescents in south-central and southeast Asia. Two typhoid vaccines are commercially available, Ty21a (oral) and Vi polysaccharide (parenteral), but neither is used routinely. Other vaccines, such as a new, modified, conjugated Vi vaccine called Vi-rEPA, are in development.\\ud \\ud Objectives\\ud To evaluate the efficacy and adverse effects of vaccines used t...

  2. Epidemiology and population structure of serotypes 1, 5 and 7f carried by children in Portugal from 1996-2010 before introduction of the 10-valent and 13-valent pneumococcal conjugate vaccines.

    Directory of Open Access Journals (Sweden)

    Sónia T Almeida

    Full Text Available Among the over 90 serotypes of Streptococcus pneumoniae described, serotypes 1, 5, and 7F account for a significant proportion of invasive disease worldwide and are now covered by the most recent 10- and 13-valent pneumococcal conjugate vaccines (PCVs. The epidemiology of these serotypes in carriage remains poorly studied because they are rarely detected. We aimed to gain insights into the epidemiology and population structure of serotypes 1, 5 and 7F carried by children in Portugal before PCV10 and PCV13 became widely used. Isolates obtained in cross-sectional studies carried out over a 15-year period (1996-2010 were retrospectively pooled and characterized. Of 5,123 pneumococci obtained, 70 were associated with serotypes 1 (n = 21, 5 (n = 7, and 7F (n = 42. The highest prevalence detected was 3.3% for serotype 1 in 2006, 1% for serotype 5 in 2009, and 3.3% for serotype 7F in 2006; Serotype 1 was associated with PMEN international clones Sweden(1-28(ST306 and Sweden(1-40(ST304; serotype 5 was associated with Colombia(5-19(ST289; and serotype 7F was associated with Netherlands(7F-39(ST191. All these isolates were fully susceptible. Most carriers of serotypes 1 (86%, 5 (86%, and 7F (91% were older than two years but a significant association with older age was only observed for serotype 7F (p = 0.006. Evidence for cross-transmission was obtained. In conclusion, we were able to detect and characterize the rarely carried serotypes 1, 5, and 7F among healthy children in Portugal. These data will constitute an important baseline for upcoming surveillance studies aimed to establish the impact of novel PCVs targeting these serotypes in carriage.

  3. Serotypes, antimicrobial susceptibility, and molecular epidemiology of invasive and non-invasive Streptococcus pneumoniae isolates in paediatric patients after the introduction of 13-valent conjugate vaccine in a nationwide surveillance study conducted in Japan in 2012-2014.

    Science.gov (United States)

    Nakano, Satoshi; Fujisawa, Takao; Ito, Yutaka; Chang, Bin; Suga, Shigeru; Noguchi, Taro; Yamamoto, Masaki; Matsumura, Yasufumi; Nagao, Miki; Takakura, Shunji; Ohnishi, Makoto; Ihara, Toshiaki; Ichiyama, Satoshi

    2016-01-02

    Pneumococcal infection in children is a major public health problem worldwide, including in Japan. The pneumococcal conjugate vaccine 7 (PCV7) was licensed for use in Japan in 2010 followed by PCV13 in 2013. This report includes the results of a nationwide surveillance of invasive pneumococcal disease (IPD) and non-IPD in paediatric patients from January 2012 to December 2014. We collected 343 isolates from 337 IPD patients and 286 isolates from 278 non-IPD patients. Of the IPD isolates, the most identified serotypes included 19A, 24F, and 15A. The prevalence of non-PCV13 serotype isolates increased significantly from 2012 to 2014 (51.6-71.4%, p=0.004). Serotypes 19A, 15A and 35B were highly non-susceptible to penicillin, and the rates of non-susceptible isolates from IPD patients to penicillin and cefotaxime significantly declined during the study period (p=0.029 and p=0.013, respectively). The non-susceptible rate to meropenem increased, particularly for serotype 15A. The IPD isolates comprised clonal complex (CC) 3111 (93.8% was serotype 19A) followed by CC2572 (81.5% was serotype 24F) and CC63 (97.1% was serotype 15A). CC3111, CC63 and CC156 (33.3% was serotype 23A, 28.6% was serotype 6B, and 14.3% was serotype 19A) were highly non-susceptible to penicillin. Of the non-IPD isolates, the most identified serotypes included 19A, 15A, and 3. In conclusion, the introduction of PCV7 and PCV13 resulted in increasing non-PCV13 serotypes and clones, including antimicrobial resistant serotypes 15A and CC63 (Sweden(15A)-25 clone).

  4. Vaccines, our shared responsibility.

    Science.gov (United States)

    Pagliusi, Sonia; Jain, Rishabh; Suri, Rajinder Kumar

    2015-05-05

    The Developing Countries Vaccine Manufacturers' Network (DCVMN) held its fifteenth annual meeting from October 27-29, 2014, New Delhi, India. The DCVMN, together with the co-organizing institution Panacea Biotec, welcomed over 240 delegates representing high-profile governmental and nongovernmental global health organizations from 36 countries. Over the three-day meeting, attendees exchanged information about their efforts to achieve their shared goal of preventing death and disability from known and emerging infectious diseases. Special praise was extended to all stakeholders involved in the success of polio eradication in South East Asia and highlighted challenges in vaccine supply for measles-rubella immunization over the coming decades. Innovative vaccines and vaccine delivery technologies indicated creative solutions for achieving global immunization goals. Discussions were focused on three major themes including regulatory challenges for developing countries that may be overcome with better communication; global collaborations and partnerships for leveraging investments and enable uninterrupted supply of affordable and suitable vaccines; and leading innovation in vaccines difficult to develop, such as dengue, Chikungunya, typhoid-conjugated and EV71, and needle-free technologies that may speed up vaccine delivery. Moving further into the Decade of Vaccines, participants renewed their commitment to shared responsibility toward a world free of vaccine-preventable diseases. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  5. 以重组肺炎球菌表面黏附素A 为载体蛋白的流感嗜血杆菌多糖结合疫苗的实验研究%Evaluation of the immunogenicity and efficacy of a Hib polysaccharide-protein conjugate vaccine by using PsaA as carrier protein

    Institute of Scientific and Technical Information of China (English)

    陈泽宇; 郭蓉; 徐江红; 吴娟; 薛红刚; 范小勇

    2014-01-01

    Objective To prepare a conjugate vaccine by linking Haemophilus influenzae type b (Hib)polysaccharide to PsaA protein carrier and evaluate the immunogenicity and efficacy of the conjugate vaccine. Methods A recombinant protein rPsaA,expressed by using the genetic engineering technology, was used as a protein carrier to prepare conjugate vaccine together with Hib polysaccharide. Ten mice at age of 3 weeks were immunized with the conjugate vaccine,while another 10 age-matched mice were immunized with Hib-tetanus toxoid(Hib-TT)vaccine which was produced formerly as a control. The mice treated with equal volume of PBS were set up as the negative control. The IgG antibodies in serum samples against PsaA and Hib polysaccharide were detected in two weeks after the final immunization. A suspension of Pneumococ-cus was injected into the middle ears of mice from experiment and control group. Histopathological analysis was performed to measure the clearance of bacteria in the middle ears and the severity of infection on days 3 and 7 after bacterial challenge. Results The rPsaA protein was prepared by the genetic engineering tech-nology and purified successfully with anion-exchange column. The Hib polysaccharide-PsaA protein conju-gate vaccine was prepared through a series of amide condensation reactions. The detection of IgG antibodies against PsaA protein and Hib polysaccharide in the immunized mice demonstrated that there was no signifi-cant difference with the titer of IgG against Hib polysaccharide between the mice immunized with the Hib-PsaA conjugate vaccine and those immunized with the Hib-TT vaccine. Less Pneumococcus strains were de-tected in the middle ears of mice immunized with the conjugate vaccine than those mice immunized with the Hib-TT vaccine three days after challenge. The mice from control group showed severe inflammation in the middle ears than those from experiment group. The Hib polysaccharide-PsaA protein conjugate vaccine im-proved protection against

  6. HPV vaccine

    Science.gov (United States)

    ... cervix - HPV vaccine; Abnormal Pap smear - HPV vaccine; Vaccination - HPV vaccine ... and Gynecologists. Committee opinion No. 641: human papillomavirus vaccination. Obstet Gynecol . 2015;126(3):e38-e43. PMID: ...

  7. Polysaccharide-specific memory B cells generated by conjugate vaccines in humans conform to the CD27+IgG+ isotype-switched memory B Cell phenotype and require contact-dependent signals from bystander T cells activated by bacterial proteins to differentiate into plasma cells.

    Science.gov (United States)

    Clarke, Edward T; Williams, Neil A; Findlow, Jamie; Borrow, Ray; Heyderman, Robert S; Finn, Adam

    2013-12-15

    The polysaccharides (PS) surrounding encapsulated bacteria are generally unable to activate T cells and hence do not induce B cell memory (BMEM). PS conjugate vaccines recruit CD4(+) T cells via a carrier protein, such as tetanus toxoid (TT), resulting in the induction of PS-specific BMEM. However, the requirement for T cells in the subsequent activation of the BMEM at the time of bacterial encounter is poorly understood, despite having critical implications for protection. We demonstrate that the PS-specific BMEM induced in humans by a meningococcal serogroup C PS (Men C)-TT conjugate vaccine conform to the isotype-switched (IgG(+)CD27(+)) rather than the IgM memory (IgM(+)CD27(+)) phenotype. Both Men C and TT-specific BMEM require CD4(+) T cells to differentiate into plasma cells. However, noncognate bystander T cells provide such signals to PS-specific BMEM with comparable effect to the cognate T cells available to TT-specific BMEM. The interaction between the two populations is contact-dependent and is mediated in part through CD40. Meningococci drive the differentiation of the Men C-specific BMEM through the activation of bystander T cells by bacterial proteins, although these signals are enhanced by T cell-independent innate signals. An effect of the TT-specific T cells activated by the vaccine on unrelated BMEM in vivo is also demonstrated. These data highlight that any protection conferred by PS-specific BMEM at the time of bacterial encounter will depend on the effectiveness with which bacterial proteins are able to activate bystander T cells. Priming for T cell memory against bacterial proteins through their inclusion in vaccine preparations must continue to be pursued.

  8. 冻干A+C群脑膜炎球菌多糖结合疫苗安全性评估%Safety Evaluation of Group A and Group C Meningococcal Polysaccharide Conjugate Vaccine (Freeze-dried)

    Institute of Scientific and Technical Information of China (English)

    刘丹青; 罗献伟; 苏颖; 陆志坚; 王晓萍; 方大春; 潘贵霞; 张怀忠; 夏志才

    2013-01-01

    Objective To evaluate the safety of group A and group C meningococcal polysaccharide conjugate vaccine (freeze-dried)(MPCV-Fd/A+C) which widely used in infants and young children.Methods Stratified cluster sampling method was used to collect 6 to 23 months of age group over 100 thousand people inoculated with 2 doses of MPCV-Fd/A+C in 5 cities of Anhui province.The interval of two doses is one month,each dose is with 0.5ml,containing group A and group C polysaccharide 10μg respectively.Observing the side effect in 30 minutes and 24,48,72 hours after vaccination.Observation ended if there was no report of any adverse events after 7 days.Observation and recording of the side reaction were conducted according to the case report form (inoculation diary cards).Results There were 100,155 people who inoculated MPCV-Fd/A+C.The analysis showed that the rate of fever was 2.57 % after inoculating the first dose within 3 days and that reduced day by day; and the systemic side effect rates of allergy,irritability,lethargy,anorexia,vomiting,diarrhea were 0.04%,0.12%,0.05%,0.06%,0.05% and 0.09% respectively; and the local side effect rates of pain,redness,swelling reaction,subcutaneous induration were 0.03 %,0.05 %,0.04%,0.02% respectively.After the second dose,all side effect rates were reduced.And 90% reaction were mild and grade 4 reaction did not occur.Conclusion The side effect rate of MPCV-Fd/A+C was mild and lower after widely used in infants and young children,it was safe.%目的 评价冻干A+C群脑膜炎球菌多糖结合疫苗(Group A and Group C Meningococcal Polysaccharide Conjugate Vaccine,Freeze-dried; MPCV-Fd/A+C),在婴幼儿中大规模使用后的安全性.方法 采用分层整群抽样,在安徽省5个市,对>10万名6~23月龄婴幼儿接种2剂MPCV-Fd/A+C,2剂间隔1个月,每剂0.5毫升(ml),含A群、C群荚膜多糖各10微克(μg).接种后进行30min即时反应观察,以及24、48、72h的随访观察,接种后第7天如

  9. Quantitative Determination of Free Polysaccharide Content in Haemophilus influenzae Type b Conjugate Vaccine by Acid Precipitation with Sodium Deoxycholate%脱氧胆酸钠酸沉淀法定量测定b型流感嗜血杆菌结合疫苗中游离多糖的含量

    Institute of Scientific and Technical Information of China (English)

    袁军; 李新国; 瞿明霞

    2011-01-01

    目的 建立一种b型流感嗜血杆菌(Haemophilus influenzae type b,Hib)结合疫苗中游离多糖含量新的检测方法.方法 分别对标准蛋白溶液、多糖溶液和标加衍生多糖(A H-PRP)的结合物原液进行脱氧胆酸钠(NaDC)酸沉淀处理,观察该方法 对蛋白和多糖的沉淀效果.分别采用NaDC酸沉淀法和乙醇分步沉淀法测定结合疫苗原液中的游离多糖含量.结果 不同浓度的标准蛋白溶液经NaDC酸沉淀法处理后,沉淀中蛋白的回收率在96%~ 99%之间;不同浓度的多糖溶液经NaDC酸沉淀法处理后,上清中的多糖回收率在99%~106%之间;该方法 对结合物中的游离多糖能起到很好的分离效果;两种方法 测定结合疫苗原液中的游离多糖含量差异有统计学意义(P<0.01).结论 NaDC酸沉淀法能专一性地沉淀蛋白物质,对游离多糖无沉淀作用,该方法 具有良好的重复性和准确性,可用于测定Hib结合疫苗中的游离多糖含量.%Objective To develop a novel method for determination of free polysaccharide content in Haemophilus influenzae type b (Hib) conjugate vaccine. Methods Standard protein solution, polysaccharide solution and bulk of conjugate added with polysaccharide derivative were treated by acid precipitation with sodium deoxycholate (NaDC ) and observed for precipitation effect of protein and polysaccharide. The free polysaccharide content in bulk of conjugate vaccine was determined by acid precipitation with NaDC and fractional precipitation with ethanol respectively. Results After acid precipitation with NaDC, the recovery rates of protein in precipitate of standard protein solution at various concentrations were 96% ~ 99%, while those of polysaccharide in supernatant of polysaccharide solution were 99% ~ 106%. The free polysaccharide in conjugate was effectively separated by the developed method. The free polysaccharide contents in bulk of conjugate vaccine determined by acid

  10. Vaccine process technology.

    Science.gov (United States)

    Josefsberg, Jessica O; Buckland, Barry

    2012-06-01

    The evolution of vaccines (e.g., live attenuated, recombinant) and vaccine production methods (e.g., in ovo, cell culture) are intimately tied to each other. As vaccine technology has advanced, the methods to produce the vaccine have advanced and new vaccine opportunities have been created. These technologies will continue to evolve as we strive for safer and more immunogenic vaccines and as our understanding of biology improves. The evolution of vaccine process technology has occurred in parallel to the remarkable growth in the development of therapeutic proteins as products; therefore, recent vaccine innovations can leverage the progress made in the broader biotechnology industry. Numerous important legacy vaccines are still in use today despite their traditional manufacturing processes, with further development focusing on improving stability (e.g., novel excipients) and updating formulation (e.g., combination vaccines) and delivery methods (e.g., skin patches). Modern vaccine development is currently exploiting a wide array of novel technologies to create safer and more efficacious vaccines including: viral vectors produced in animal cells, virus-like particles produced in yeast or insect cells, polysaccharide conjugation to carrier proteins, DNA plasmids produced in E. coli, and therapeutic cancer vaccines created by in vitro activation of patient leukocytes. Purification advances (e.g., membrane adsorption, precipitation) are increasing efficiency, while innovative analytical methods (e.g., microsphere-based multiplex assays, RNA microarrays) are improving process understanding. Novel adjuvants such as monophosphoryl lipid A, which acts on antigen presenting cell toll-like receptors, are expanding the previously conservative list of widely accepted vaccine adjuvants. As in other areas of biotechnology, process characterization by sophisticated analysis is critical not only to improve yields, but also to determine the final product quality. From a regulatory

  11. 用于Hib结合疫苗生产的新型候选菌株的评价%Evaluation on a new candidate strain for Haemophilus influenzae type b conjugate vaccine production

    Institute of Scientific and Technical Information of China (English)

    王伟; 马雷钧; 王月红; 朱为; 马相虎

    2011-01-01

    目的 观察b型流感嗜血杆菌(Haemophilus influenzae type b,Hib)760705株在连续传代过程中的稳定性.方法 将Hib 760705株工作种子批菌种连续传代,对第5、第8、第10代Hib培养物进行全面检测,包括培养特性(细菌培养、卫星试验)、染色镜检、生化反应,以检测第5、第8、第10代Hib的生物学特性.同时采用血清凝集试验和聚合酶链反应荚膜分型方法进行b型荚膜多糖稳定性检测.结果 Hib 760705株工作种子批培养物在连续传代过程中具有典型的细菌学特性,能够稳定地产生b型荚膜多糖.结论 Hib 760705株有明确的来源和背景,可以稳定传代,具备作为Hib结合疫苗生产用候选菌株的条件.%Objective To observe the passage stability of Haemophilus influenzae type b(Hib) strain 760705. Methods Hib strain 760705 was cultured for 10 passages from the working seed lot, and the subcultures of the 5th, 8th and 10th passages were detected for biological charactristics comprehensively,including cultural characteristics( bacterial culture and satellite test), staining and microscopic examination,and biochemical reactions. Serological agglutination test and polymerase chain reaction for capsular typing were applied to confirm the generation stability of type b capsular polysaccharide. Results The subcultures of Hib strain 760705 had typical bacteriological characteristics and capability of yielding type b capsular polysaccharide. Conclusions Hib strain 760705 has a clear origin and background and can be subcultured stably, thus suggesting that it can be a candidate strain for Hib conjugate vaccine production.

  12. Comparative estimation of coverage between national immunization program vaccines and non-NIP vaccines in Korea.

    Science.gov (United States)

    Choe, Young June; Yang, Jae Jeong; Park, Sue K; Choi, Eun Hwa; Lee, Hoan Jong

    2013-09-01

    This study aimed to describe the differences in vaccination coverage between National Immunization Program (NIP) vaccines and non-NIP vaccines in Korea and to identify factors affecting the difference. Nationwide face-to-face interview-based questionnaire survey among randomly selected 4,374 participants aged 7-83 months was conducted. Vaccination coverage analyzed according to the birth cohorts, geographic areas, and socio-demographic characteristics. We found that NIP vaccines recorded higher primary vaccination coverage compared to non-NIP vaccines (95.9%-100% vs 30.7%-85.4%). The highest rate was Haemophilus influenzae type b (Hib) vaccine (85.4%), which was introduced in 1996, and the lowest rate was rotavirus vaccine (30.7%), which was introduced recently. On multivariate analysis, having a sibling were significantly associated with lower uptake of Hib vaccine, pneumococcal conjugate vaccine (PCV), and rotavirus vaccine; while, older mother's age and attendance to daycare center were significantly associated with lower uptake of PCV and rotavirus vaccine (P < 0.001). We found differences in the vaccine coverage rate between NIP vaccines and non-NIP vaccines; and the data suggests potential disparity in accessing non-NIP vaccines in Korea. Expansion of NIP to include non-NIP vaccines can provide better protection against the diseases through increased coverage.

  13. Vaccine Safety

    Science.gov (United States)

    ... Vaccine Safety Shingles (Herpes Zoster) Vaccine Safety Smallpox Vaccine Safety Common Concerns Adjuvants Autism CDC Statement: 2004 Pediatrics Paper on MMR and Autism Fainting (Syncope) Febrile ...

  14. Pneumococcal Vaccination Recommendations for Children and Adults by Age and/or Risk Factor

    Science.gov (United States)

    Pneumococcal Vaccination Recommendations for Children 1 and Adults by Age and/or Risk Factor Routine Recommendations for Pneumococcal Conjugate ... X X X X X 1 For PCV13 vaccination of healthy children, see “Recommen- dations for Pneumococcal ...

  15. A combined Haemophilus influenzae type B Neisseria meningitidis serogroup C tetanus toxoid conjugate vaccine is immunogenic and well-tolerated when coadministered with diphtheria, tetanus, acellular pertussis hepatitis B-inactivated poliovirus at 3, 5 and 11 months of age: results of an open, randomized, controlled study.

    Science.gov (United States)

    Vesikari, Timo; Forstén, Aino; Desole, Maria Guiseppina; Ferrera, Giuseppe; Caubet, Magalie; Mesaros, Narcisa; Boutriau, Dominique

    2013-05-01

    This study evaluated the immunogenicity, reactogenicity and safety of the combined Haemophilus influenzae type B Neisseria meningitidis serogroup C tetanus toxoid conjugate vaccine (Hib-MenC-TT) coadministered with diphtheria, tetanus, acellular pertussis hepatitis B-inactivated poliovirus (DTPa-HBV-IPV) as 2 primary and 1 booster doses at 3, 5 and 11 months of age. In this phase III open study (NCT00327184), 709 infants were randomized in 2 parallel groups (1:1) to receive either Hib-MenC-TT coadministered with DTPa-HBV-IPV or control vaccines (MenC-TT coadministered with DTPa-HBV-IPV/Hib). Serum bactericidal activity for MenC (rSBA-MenC) and antibody concentrations against polyribosylribitol phosphate from Hib (anti-PRP) and hepatitis B (anti-HBs) were measured at 1 month after dose 2, before booster and 1 month after booster dose. Solicited (local/general) and unsolicited symptoms were assessed up to 4 and 31 days, respectively, after each vaccination. Serious adverse events were recorded throughout the study. One month after dose 2, high percentages of infants in both groups had rSBA-MenC titers ≥ 8 (≥ 99.1%), anti-PRP concentrations ≥ 0.15 μg/mL (≥ 96.5%) and anti-HBs concentrations ≥ 10 mIU/mL (≥ 95.3%), which persisted up to the booster vaccination (≥ 94.5%, ≥ 86.1%, ≥ 94.2%) and increased again after the booster dose (100%, 100%, ≥ 99%). Exploratory analyses indicated that rSBA-MenC geometric mean titers were lower and anti-PRP geometric mean concentrations were higher in the infants vaccinated with Hib-MenC-TT compared with the control vaccines at all time points. The safety profiles of the coadministered vaccines were similar in both groups. The Hib-MenC-TT and DTPa-HBV-IPV vaccines are immunogenic with a clinically acceptable safety profile when coadministered as 2 primary doses during infancy and 1 booster dose at 11 months of age.

  16. Pneumococcal conjugate vaccines for preventing otitis media

    NARCIS (Netherlands)

    Fortanier, Alexandre C.; Venekamp, Roderick P.; Boonacker, Chantal W. B.; Hak, Eelko; Schilder, Anne G. M.; Sanders, Elisabeth A. M.; Damoiseaux, Roger A. M. J.

    2014-01-01

    BACKGROUND: Acute otitis media (AOM) is a very common respiratory infection in early infancy and childhood. The marginal benefits of antibiotics for AOM in low-risk populations in general, the increasing problem of bacterial resistance to antibiotics and the huge estimated direct and indirect annual

  17. Pneumococcal conjugate vaccines for preventing otitis media

    NARCIS (Netherlands)

    Fortanier, Alexandre C.; Venekamp, Roderick P.; Boonacker, Chantal W. B.; Hak, Eelko; Schilder, Anne G. M.; Sanders, Elisabeth A. M.; Damoiseaux, Roger A. M. J.

    2014-01-01

    BACKGROUND: Acute otitis media (AOM) is a very common respiratory infection in early infancy and childhood. The marginal benefits of antibiotics for AOM in low-risk populations in general, the increasing problem of bacterial resistance to antibiotics and the huge estimated direct and indirect annual

  18. Pneumococcal conjugate vaccines for preventing otitis media

    NARCIS (Netherlands)

    Jansen, Angelique G S C; Hak, Eelko; Veenhoven, Reinier H; Damoiseaux, Roger A M J; Schilder, Anne G M; Sanders, Elisabeth A M

    2009-01-01

    BACKGROUND: Acute otitis media (AOM) is a very common early infancy and childhood disease. The marginal benefits of antibiotics on AOM, the increasing problem of bacterial resistance to antibiotics, and the huge estimated direct and indirect annual costs associated with otitis media (OM) have prompt

  19. 测定b型流感嗜血杆菌结合疫苗游离多糖的脱氧胆酸钠沉淀法的建立%Establishment of a sodium deoxycholate precipitation method for determination of the free polysaccharide in Haemophilus influenzae type b conjugate vaccine

    Institute of Scientific and Technical Information of China (English)

    沈坚; 梁芳; 方曼莉; 王伟; 赵菲琼; 马相虎

    2014-01-01

    目的 建立测定b型流感嗜血杆菌(Haemophilus in fluenzae type b,Hib)结合疫苗游离多糖的脱氧胆酸钠(sodium deoxycholate,DOC)沉淀法.方法 在一定的酸性条件下,用1%DOC沉淀分离Hib结合疫苗中的结合多糖和游离多糖,测定上清和沉淀的多糖含量,并对该法进行验证.结果 DOC沉淀法的标准曲线具有可靠的线性,决定系数>0.999.该法的准确性和精密度良好,多糖加样回收率为103%~108%,相对标准偏差均<10%.结论 建立的DOC沉淀法可用于Hib结合疫苗中的游离多糖测定.%Objective To establish a sodium deoxycholate precipitation method for determination of the free polysaccharide in Haemophilus influenzae type b (Hib) conjugate vaccine.Methods The conjugated and the free polysaccharides were separated using 1 % sodium deoxycholate (DOC) under certain conditions.The contents of free polysaccharide in supernatant and precipitate were detected.The DOC precipitation method was validated.Results The standard curve of the DOC precipitation method had good linearity and the coefficient of determination was >0.999.The DOC precipitation method had good accuracy and precision.Recoveries and relative standard deviations of the establish method were 103%-108% and <10%,respectively.Conclusion The established DOC precipitation method can be used to detect the free polysaccharide in Hib conjugate vaccine.

  20. Dendrimers for Vaccine and Immunostimulatory Uses

    DEFF Research Database (Denmark)

    Heegaard, Peter M. H.; Boas, Ulrik; Sørensen, Nanna Skall

    2010-01-01

    for efficient immunostimulating compounds (adjuvants) that can increase the efficiency of vaccines, as dendrimers can provide molecularly defined multivalent scaffolds to produce highly defined conjugates with small molecule immunostimulators and/or antigens. The review gives an overview on the use...... of dendrimers as molecularly defined carriers/presenters of small antigens, including constructs that have built-in immunostimulatory (adjuvant) properties, and as stand-alone adjuvants that can be mixed with antigens to provide efficient vaccine formulations. These approaches allow the preparation...... of molecularly defined vaccines with highly predictable and specific properties and enable knowledge-based vaccine design substituting the traditional empirically based approaches for vaccine development and production....

  1. Antimicrobial susceptibility of Streptococcus pneumoniae isolates from vaccinated and non-vaccinated patients with a clinically confirmed diagnosis of community-acquired pneumonia in Belgium.

    Science.gov (United States)

    Lismond, Ann; Carbonnelle, Sylviane; Verhaegen, Jan; Schatt, Patricia; De Bel, Annelies; Jordens, Paul; Jacobs, Frédérique; Dediste, Anne; Verschuren, Frank; Huang, Te-Din; Tulkens, Paul M; Glupczynski, Youri; Van Bambeke, Françoise

    2012-03-01

    We assessed the in vitro susceptibility of Streptococcus pneumoniae isolates from patients with confirmed community-acquired pneumonia (CAP) to β-lactams, macrolides and fluoroquinolones and the association of non-susceptibility and resistance with serotypes/serogroups (STs/SGs), patient's risk factors and vaccination status. Samples (blood or lower respiratory tract) were obtained in 2007-2009 from 249 patients (from seven hospitals in Belgium) with a clinical and radiological diagnosis of CAP [median age 61 years (11.6% aged 94% ST19A), 73.5% resistant to macrolides and 18-21% intermediate to β-lactams; and SG6, 33% resistant to clarithromycin. Apparent vaccine failures: 3/17 for 7-valent vaccine (children; ST6B, 23F); 16/29 for 23-valent vaccine (adults ST3, 7F, 12F, 14, 19A, 22F, 23F, 33F). Isolates from nursing home residents, hospitalised patients and patients with non-respiratory co-morbidities showed increased MICs for amoxicillin, all β-lactams, and β-lactams and macrolides, respectively. Regarding antibiotic susceptibilities: (i) amoxicillin is still useful for empirical therapy but with a high daily dose; (ii) cefuroxime axetil and macrolides (but not telithromycin) are inappropriate for empirical therapy; and (iii) moxifloxacin and levofloxacin are the next 'best empirical choice' (no resistant isolates) but levofloxacin will require 500 mg twice-daily dosing for effective coverage.

  2. Metal-leachate-induced conjugate protein instability.

    Science.gov (United States)

    Li, Ning; Osborne, Brandi; Singh, Satish K; Wang, Wei

    2012-08-01

    During the scale-up of an ultrafiltration/diafiltration (UF/DF) step for a protein-based conjugate vaccine, significant precipitation was observed at room temperature. It was found that a specific type of metal hosebarb fitting used in the UF/DF system, when placed in the conjugate solution, caused the precipitation. Inductively Coupled Plasma Mass Spectrometry analysis showed significant amounts of Ni(II), Zn(II), and Cu(II) present in the conjugate solution. A kinetic study showed that the concentration of these metal ions gradually increased with increasing incubation time with a corresponding decrease in conjugate concentration. Direct spiking of trace amounts of NiCl₂, ZnCl₂, and CuCl₂ into the conjugate solution also caused precipitation, and spiking studies showed that the metal ions caused precipitation of the conjugate but not of the carrier protein, antigen, or carrier protein + linker. The precipitation was found to be significantly dependent on buffer species but not solution pH and led to an irreversible loss of tertiary structure even after dissolution in and removal of guanidine hydrochloride. The precipitation is likely the result of formation of transition-metal complexes with histidine residues on the antigen peptide, which may involve both intraconjugate and interconjugate antigens. Such complexation may lead to formation of multimers that may exceed the solubility limit.

  3. Travel advice for the immunocompromised traveler: prophylaxis, vaccination, and other preventive measures [Corrigendum

    Directory of Open Access Journals (Sweden)

    Patel RR

    2015-04-01

    Full Text Available Patel RR, Liang SY, Koolwal P, Kuhlmann FM. Therapeutics and Clinical Risk Management. 2015;11:217–228.On page 224, Meningococcal vaccine heading, second sentence “Vaccination is recommended with the quadrivalent polysaccharide (Menactra™” should have read “Vaccination with the quadrivalent meningococcal conjugate vaccine (MCV4 is recommended”. Read the original paper

  4. O:2-CRM(197) conjugates against Salmonella Paratyphi A.

    Science.gov (United States)

    Micoli, Francesca; Rondini, Simona; Gavini, Massimiliano; Lanzilao, Luisa; Medaglini, Donata; Saul, Allan; Martin, Laura B

    2012-01-01

    Enteric fevers remain a common and serious disease, affecting mainly children and adolescents in developing countries. Salmonella enterica serovar Typhi was believed to cause most enteric fever episodes, but several recent reports have shown an increasing incidence of S. Paratyphi A, encouraging the development of a bivalent vaccine to protect against both serovars, especially considering that at present there is no vaccine against S. Paratyphi A. The O-specific polysaccharide (O:2) of S. Paratyphi A is a protective antigen and clinical data have previously demonstrated the potential of using O:2 conjugate vaccines. Here we describe a new conjugation chemistry to link O:2 and the carrier protein CRM(197), using the terminus 3-deoxy-D-manno-octulosonic acid (KDO), thus leaving the O:2 chain unmodified. The new conjugates were tested in mice and compared with other O:2-antigen conjugates, synthesized adopting previously described methods that use CRM(197) as carrier protein. The newly developed conjugation chemistry yielded immunogenic conjugates with strong serum bactericidal activity against S. Paratyphi A.

  5. Pneumococcal conjugate vaccine: A newer vaccine available in India

    OpenAIRE

    Verma, Ramesh; Khanna, Pardeep

    2012-01-01

    Streptococcus pneumoniae, or “pneumococcus,” causes pneumonia and infections of the brain and blood that are responsible for significant mortality in children under five years as well as in the elderly. Pneumococcal diseases are a major public health problem worldwide. S. pneumoniae is responsible for 15–50% of all episodes of community-acquired pneumonia, 30–50% of all cases of acute otitis media, and a significant proportion of bacterial meningitis and bacteremia. S. pneumoniae kills at lea...

  6. [Incidence of admissions due to pneumonia in children under 24 months old before and after the introduction of the 10-valent pneumococcal conjugate vaccine into the National Immunization Program of Chile].

    Science.gov (United States)

    Fernández V, José Pablo; Goecke H, Carola; von Borries, Cecilia; Tapia R, Natalia; Santolaya de P, María Elena

    2015-01-01

    Streptococcus pneumoniae is the leading cause of bacterial pneumonia in children, especially in the hospitalized population. The 10-valent pneumococcal vaccine was included in the National Immunization Program of Chile in 2011. This study aims to evaluate the incidence of pneumonia in hospitalized children<24 months of age in the Luis Calvo Mackenna Hospital before and after the introduction of the pneumococcal vaccine into the National Immunization Program. Passive surveillance study. Patients<24 months with discharge diagnosis of bacterial pneumonia from Luis Calvo Mackenna Hospital were studied between 2009 and 2013. Data were obtained from the Luis Calvo Mackenna Hospital's Statistical Service. The incidence of pneumonia was evaluated in the pre-vaccination period (2009-2010) and in the post-vaccination period (2012-2013). During the study period, an average of 4,321 discharges/year was observed in children<24 months (range: 3,587-4,702), with a significant decrease from pre- to post-vaccination vaccine period (4,644 vs 4,013, P<.001). The average incidence of pneumonia ranged from 3.4/100,000 to 1.5/100,000 in the pre- and post-vaccine period, respectively (P=.009), with an annual mean of 157 cases of pneumonia in the pre- vaccine period, and 62 cases in the postvaccine period (P<.001) and a decrease in incidence between the two periods of 56%. This study confirms information previously obtained in other countries, which show a decrease in the incidence of pneumonia associated with the implementation of a pneumococcal vaccine at the population level. Ongoing surveillance is required to evaluate if this effect is maintained over time and expands to older populations. Copyright © 2015 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  7. Revisiting conjugate schedules.

    Science.gov (United States)

    MacAleese, Kenneth R; Ghezzi, Patrick M; Rapp, John T

    2015-07-01

    The effects of conjugate reinforcement on the responding of 13 college students were examined in three experiments. Conjugate reinforcement was provided via key presses that changed the clarity of pictures displayed on a computer monitor in a manner proportional to the rate of responding. Experiment 1, which included seven parameters of clarity change per response, revealed that responding decreased as the percentage clarity per response increased for all five participants. These results indicate that each participant's responding was sensitive to intensity change, which is a parameter of conjugate reinforcement schedules. Experiment 2 showed that responding increased during conjugate reinforcement phases and decreased during extinction phases for all four participants. Experiment 3 also showed that responding increased during conjugate reinforcement and further showed that responding decreased during a conjugate negative punishment condition for another four participants. Directions for future research with conjugate schedules are briefly discussed.

  8. CASE REPORT OF CEREBRAL ATROPHY INDUCED BY HAEMOPHILUS INFLUENZA TYPE B CONJUGATE VACCINE%b型流感嗜血杆菌结合疫苗致脑萎缩病例报告

    Institute of Scientific and Technical Information of China (English)

    王仁富; 廖红英

    2012-01-01

    [目的]对接种某种b型流感嗜血杆菌结合疫苗后发生脑萎缩的个案进行分析,结合该个案提出对避免预防接种异常反应工作提出建议.[方法]个案分析.[结果]患儿的脑萎缩是接种疫苗后发生抽搐、发热、意识障碍等症状产生的后遗症.[结论]预防接种工作人员在接种疫苗时须加强安全意识,避免异常反应的发生.%[Objective] To analyze the cases with brain atrophy induced by vaccination with Haemophilus influenzae type b vaccine, combined with the case put forward to avoid abnormal reaction to the work of vaccination recommendations. [Methods] Case report analysis was taken. [RssultS] Children with brain atrophy is the occurrence of seizures after vaccination, fever, disturbance of consciousness and olher symptoms resulting sequela. [Conclusion] Vaccination of staff should be vaccinated to enhance safety awareness and prevent the occurrence of abnormal reaction.

  9. Advances with vaccination against Neisseria meningitidis.

    Science.gov (United States)

    Borrow, Ray

    2012-12-01

    In the last decade, meningococcal serogroup C conjugate vaccination programs have been demonstrated to be hugely successful with a truly impressive public health impact. In sub-Saharan Africa, with the implementation of an affordable serogroup A conjugate vaccine, it is hoped that a similar public health impact will be demonstrated. Challenges still remain in the quest to develop and implement broadly protective vaccines against serogroup B disease. New, broad coverage vaccines against serogroup B are for the first time becoming available although little is known about their antibody persistence, effectiveness or effect on nasopharyngeal carriage. Enhanced surveillance following any potential vaccine introduction against serogroup B needs to be thoroughly implemented. The future now holds a distinct possibility, globally, for substantially decreasing meningococcal disease, regardless of infecting serogroup. © 2012 Blackwell Publishing Ltd.

  10. [Travelers' vaccines].

    Science.gov (United States)

    Ouchi, Kazunobu

    2011-09-01

    The number of Japanese oversea travelers has gradually increased year by year, however they usually pay less attention to the poor physical condition at the voyage place. Many oversea travelers caught vaccine preventable diseases in developing countries. The Vaccine Guideline for Oversea Travelers 2010 published by Japanese Society of Travel Health will be helpful for spreading the knowledge of travelers' vaccine and vaccine preventable diseases in developing countries. Many travelers' vaccines have not licensed in Japan. I hope these travelers' vaccines, such as typhoid vaccine, meningococcal vaccine, cholera vaccine and so on will be licensed in the near future.

  11. Hib Vaccines: Past, Present, and Future Perspectives

    Directory of Open Access Journals (Sweden)

    Adi Essam Zarei

    2016-01-01

    Full Text Available Haemophilus influenzae type b (Hib causes many severe diseases, including epiglottitis, pneumonia, sepsis, and meningitis. In developed countries, the annual incidence of meningitis caused by bacteria is approximately 5–10 cases per population of 100,000. The Hib conjugate vaccine is considered protective and safe. Adjuvants, molecules that can enhance and/or regulate the fundamental immunogenicity of an antigen, comprise a wide range of diverse compounds. While earlier developments of adjuvants created effective products, there is still a need to create new generations, rationally designed based on recent discoveries in immunology, mainly in innate immunity. Many factors may play a role in the immunogenicity of Hib conjugate vaccines, such as the polysaccharides and proteins carrier used in vaccine construction, as well as the method of conjugation. A Hib conjugate vaccine has been constructed via chemical synthesis of a Hib saccharide antigen. Two models of carbohydrate-protein conjugate have been established, the single ended model (terminal amination-single method and cross-linked lattice matrix (dual amination method. Increased knowledge in the fields of immunology, molecular biology, glycobiology, glycoimmunology, and the biology of infectious microorganisms has led to a dramatic increase in vaccine efficacy.

  12. Safety, immunogenicity and persistence of immune response to the combined diphtheria, tetanus, acellular pertussis, poliovirus and Haemophilus influenzae type b conjugate vaccine (DTPa-IPV/Hib) administered in Chinese infants

    Science.gov (United States)

    Li, Yanping; Li, Rong Cheng; Ye, Qiang; Li, Changgui; Liu, You Ping; Ma, Xiao; Li, Yanan; Zhao, Hong; Chen, Xiaoling; Assudani, Deepak; Karkada, Naveen; Han, Htay Htay; Van Der Meeren, Olivier; Mesaros, Narcisa

    2017-01-01

    ABSTRACT We conducted 3 phase III, randomized, open-label, clinical trials assessing the safety, reactogenicity (all studies), immunogenicity (Primary vaccination study) and persistence of immune responses (Booster study) to the combined diphtheria, tetanus, pertussis, poliomyelitis, and Haemophilus influenzae type b vaccine (DTPa-IPV/Hib) in Chinese infants and toddlers. In the Pilot study (NCT00964028), 50 infants (randomized 1:1) received 3 doses of DTPa-IPV/Hib at 2–3–4 (Group A) or 3–4–5 months of age (Group B). In the Primary study (NCT01086423), 984 healthy infants (randomized 1:1:1) received 3 doses of DTPa-IPV/Hib at 2–3–4 (Group A) or 3–4–5 (Group B) months of age, or concomitant DTPa/Hib and poliomyelitis (IPV) vaccination at 2–3–4 months of age (Control group); 825 infants received a booster dose of DTPa/Hib and IPV at 18–24 months of age (Booster study; NCT01449812). In the Pilot study, unsolicited symptoms were more frequent in Group A (16 versus 1 infant; mostly upper respiratory tract infection and pyrexia); this observation was attributed to an epidemic outbreak of viral infections. Non-inferiority of 3-dose primary vaccination with DTPa-IPV/Hib over separately administered DTPa/Hib and IPV was demonstrated for Group A (primary objective). Similar antibody concentrations were observed in all groups, except for anti-polyribosyl-ribitol phosphate and anti-poliovirus types 1–3 which were higher in DTPa-IPV/Hib recipients. Protective antibody levels against all vaccine antigens remained high until booster vaccination. Three-dose vaccination with DTPa-IPV/Hib had a clinically acceptable safety profile. PMID:27768515

  13. Production of glycoprotein vaccines in Escherichia coli

    Directory of Open Access Journals (Sweden)

    Ihssen Julian

    2010-08-01

    Full Text Available Abstract Background Conjugate vaccines in which polysaccharide antigens are covalently linked to carrier proteins belong to the most effective and safest vaccines against bacterial pathogens. State-of-the art production of conjugate vaccines using chemical methods is a laborious, multi-step process. In vivo enzymatic coupling using the general glycosylation pathway of Campylobacter jejuni in recombinant Escherichia coli has been suggested as a simpler method for producing conjugate vaccines. In this study we describe the in vivo biosynthesis of two novel conjugate vaccine candidates against Shigella dysenteriae type 1, an important bacterial pathogen causing severe gastro-intestinal disease states mainly in developing countries. Results Two different periplasmic carrier proteins, AcrA from C. jejuni and a toxoid form of Pseudomonas aeruginosa exotoxin were glycosylated with Shigella O antigens in E. coli. Starting from shake flask cultivation in standard complex medium a lab-scale fed-batch process was developed for glycoconjugate production. It was found that efficiency of glycosylation but not carrier protein expression was highly susceptible to the physiological state at induction. After induction glycoconjugates generally appeared later than unglycosylated carrier protein, suggesting that glycosylation was the rate-limiting step for synthesis of conjugate vaccines in E. coli. Glycoconjugate synthesis, in particular expression of oligosaccharyltransferase PglB, strongly inhibited growth of E. coli cells after induction, making it necessary to separate biomass growth and recombinant protein expression phases. With a simple pulse and linear feed strategy and the use of semi-defined glycerol medium, volumetric glycoconjugate yield was increased 30 to 50-fold. Conclusions The presented data demonstrate that glycosylated proteins can be produced in recombinant E. coli at a larger scale. The described methodologies constitute an important step

  14. Cancer Vaccines

    Science.gov (United States)

    ... Genetics Services Directory Cancer Prevention Overview Research Cancer Vaccines On This Page What is the immune system? ... cells recognized by the immune system? What are vaccines? What are cancer vaccines? How do cancer preventive ...

  15. Leptospirosis vaccines

    Directory of Open Access Journals (Sweden)

    Jin Li

    2007-12-01

    Full Text Available Abstract Leptospirosis is a serious infection disease caused by pathogenic strains of the Leptospira spirochetes, which affects not only humans but also animals. It has long been expected to find an effective vaccine to prevent leptospirosis through immunization of high risk humans or animals. Although some leptospirosis vaccines have been obtained, the vaccination is relatively unsuccessful in clinical application despite decades of research and millions of dollars spent. In this review, the recent advancements of recombinant outer membrane protein (OMP vaccines, lipopolysaccharide (LPS vaccines, inactivated vaccines, attenuated vaccines and DNA vaccines against leptospirosis are reviewed. A comparison of these vaccines may lead to development of new potential methods to combat leptospirosis and facilitate the leptospirosis vaccine research. Moreover, a vaccine ontology database was built for the scientists working on the leptospirosis vaccines as a starting tool.

  16. Towards a sustainable, quality and affordable Haemophilus influenzae type b vaccine for every child in the world

    NARCIS (Netherlands)

    Hamidi, A.

    2016-01-01

    Haemophilus influenzae type b (Hib) conjugate vaccine is a safe and effective vaccine that can prevent meningitis and pneumonia caused by Hib disease. Hib vaccine is recommended for all children under 5 years. Despite the availability of safe and effective Hib vaccines since early 1987, Gambia was

  17. Towards a sustainable, quality and affordable Haemophilus influenzae type b vaccine for every child in the world

    NARCIS (Netherlands)

    Hamidi, A.

    2016-01-01

    Haemophilus influenzae type b (Hib) conjugate vaccine is a safe and effective vaccine that can prevent meningitis and pneumonia caused by Hib disease. Hib vaccine is recommended for all children under 5 years. Despite the availability of safe and effective Hib vaccines since early 1987, Gambia was t

  18. Vaccine Hesitancy.

    Science.gov (United States)

    Jacobson, Robert M; St Sauver, Jennifer L; Finney Rutten, Lila J

    2015-11-01

    Vaccine refusal received a lot of press with the 2015 Disneyland measles outbreak, but vaccine refusal is only a fraction of a much larger problem of vaccine delay and hesitancy. Opposition to vaccination dates back to the 1800 s, Edward Jenner, and the first vaccine ever. It has never gone away despite the public's growing scientific sophistication. A variety of factors contribute to modern vaccine hesitancy, including the layperson's heuristic thinking when it comes to balancing risks and benefits as well as a number of other features of vaccination, including falling victim to its own success. Vaccine hesitancy is pervasive, affecting a quarter to a third of US parents. Clinicians report that they routinely receive requests to delay vaccines and that they routinely acquiesce. Vaccine rates vary by state and locale and by specific vaccine, and vaccine hesitancy results in personal risk and in the failure to achieve or sustain herd immunity to protect others who have contraindications to the vaccine or fail to generate immunity to the vaccine. Clinicians should adopt a variety of practices to combat vaccine hesitancy, including a variety of population health management approaches that go beyond the usual call to educate patients, clinicians, and the public. Strategies include using every visit to vaccinate, the creation of standing orders or nursing protocols to provide vaccination without clinical encounters, and adopting the practice of stating clear recommendations. Up-to-date, trusted resources exist to support clinicians' efforts in adopting these approaches to reduce vaccine hesitancy and its impact.

  19. The first dose of a Haemophilus influenzae type b conjugate vaccine reactivates memory B cells: evidence for extensive clonal selection, intraclonal affinity maturation, and multiple isotype switches to IgA2

    DEFF Research Database (Denmark)

    Hougs, L; Juul, L; Ditzel, H J

    1999-01-01

    selected, and expanded population of cells existing before vaccination, i.e., memory B cells. The dominating heavy and light chains of the response were combined in a Fab that bound HibCP. It was shown that the shared heavy and light chain mutations increased the affinity for HibCP considerably, indicating...... that the clonal selection had been driven by affinity. Pre-existing memory cells in unvaccinated adults may explain several features of Ab responses to polysaccharide vaccines and may play a role in acquiring the ability to respond to pure polysaccharides during infancy....

  20. Polymer-protein conjugation via a 'grafting to' approach-a comparative study of the performance of protein-reactive RAFT chain transfer agents

    NARCIS (Netherlands)

    Vanparijs, N.; Maji, S.; Louage, B.; Voorhaar, L.; Laplace, D.; Shi, Y.; Hennink, W. E.; Hoogenboom, R.; De Geest, B. G.

    2015-01-01

    Efficient polymer-protein conjugation is a crucial step in the design of many therapeutic protein formulations including nanoscopic vaccine formulations, antibody-drug conjugates and to enhance the in vivo behaviour of proteins. Here we aimed at preparing well-defined polymers for conjugation to pro

  1. The efficacy and safety of a nicotine conjugate vaccine (NicVAX®) or placebo co-administered with varenicline (Champix®) for smoking cessation: study protocol of a phase IIb, double blind, randomized, placebo controlled trial

    National Research Council Canada - National Science Library

    Hoogsteder, Philippe H J; Kotz, Daniel; van Spiegel, Paul I; Viechtbauer, Wolfgang; Brauer, Ruth; Kessler, Paul D; Kalnik, Matthew W; Fahim, Raafat E F; van Schayck, Onno C P

    2012-01-01

    ... its receptors in the brain and causing the release of dopamine. The aim of this paper is to describe the design of a phase IIb, multi-center, double blind, randomized, placebo controlled trial to assess the efficacy of the nicotine vaccine...

  2. [Research and development strategies, examples among new vaccines].

    Science.gov (United States)

    Denis, F; Ploy, M-C

    2009-05-01

    Classical methods are still providing new vaccines, but molecular biology and genetic engineering have enabled new approaches to development. Changes in vaccinology have involved the isolation, presentation and administration of vaccinal antigens or attenuated vaccinal strains. New methods of vaccine delivery other than injection will be used (e.g. mucosal administration) and new vectors or adjuvants will be added to vaccines in order to stimulate specific responses. New vaccines can also be obtained by using viral-like particles (VLP of papillomavirus), conjugate polysaccharides (N. meningitidis, S. pneumoniae) or the reassortment of segmented genomes (rotavirus, influenza). Here, we analyze the different steps of a vaccine's life using concrete cases of two new vaccines against papillomavirus and rotavirus. Vaccination has a promising future.

  3. Vaccination coverage of patients with inborn errors of metabolism and the attitudes of their parents towards vaccines.

    Science.gov (United States)

    Cerutti, Marta; De Lonlay, Pascale; Menni, Francesca; Parini, Rossella; Principi, Nicola; Esposito, Susanna

    2015-11-27

    To evaluate vaccination coverage of children and adolescents with inborn errors of metabolism (IEMs) and the attitudes of their parents towards vaccination, the vaccination status of 128 patients with IEM and 128 age- and gender-matched healthy controls was established by consulting the official vaccination chart. In children with IEMs, compared with healthy controls, low vaccination rates and/or delays in administration were observed for pneumococcal conjugate, meningococcus C, measles, mumps, rubella, diphtheria-tetanus-pertussis-inactivated polio, Bacillus Calmette-Guerin, and influenza vaccines. Among the parents of IEM patients, vaccine schedule compliance was primarily driven by the doctors at the hospital's reference centres; among the parents of the healthy controls, compliance was driven by the primary care paediatricians. These results show that IEM patients demonstrate sub-optimal vaccination coverage. Further studies of the different vaccines in each IEM disorder and educational programmes aimed at physicians and parents to increase immunization coverage in these patients are urgently needed.

  4. 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.

  5. Childhood Vaccines: What They Are and Why Your Child Needs Them

    Science.gov (United States)

    ... can get a copy of the most current child and adolescent vaccination schedules from an organization, such as the American ... MMR, patient education, patient information, pneumococcal conjugate, Td, vaccination, vaccines, varicella, well-child care Family Health, Infants and Toddlers, Prevention and ...

  6. Segmented conjugated polymers

    Indian Academy of Sciences (India)

    G Padmanaban; S Ramakrishnan

    2003-08-01

    Segmented conjugated polymers, wherein the conjugation is randomly truncated by varying lengths of non-conjugated segments, form an interesting class of polymers as they not only represent systems of varying stiffness, but also ones where the backbone can be construed as being made up of chromophores of varying excitation energies. The latter feature, especially when the chromophores are fluorescent, like in MEHPPV, makes these systems particularly interesting from the photophysics point of view. Segmented MEHPPV- samples, where x represents the mole fraction of conjugated segments, were prepared by a novel approach that utilizes a suitable precursor wherein selective elimination of one of the two eliminatable groups is affected; the uneliminated units serve as conjugation truncations. Control of the composition x of the precursor therefore permits one to prepare segmented MEHPPV- samples with varying levels of conjugation (elimination). Using fluorescence spectroscopy, we have seen that even in single isolated polymer chains, energy migration from the shorter (higher energy) chromophores to longer (lower energy) ones occurs – the extent of which depends on the level of conjugation. Further, by varying the solvent composition, it is seen that the extent of energy transfer and the formation of poorly emissive inter-chromophore excitons are greatly enhanced with increasing amounts of non-solvent. A typical S-shaped curve represents the variation of emission yields as a function of composition suggestive of a cooperative collapse of the polymer coil, reminiscent of conformational transitions seen in biological macromolecules.

  7. PNEUMOCOCCAL INFECTION IN CHILDREN: OPPORTUNITIES OF PROPHYLAXIS

    Directory of Open Access Journals (Sweden)

    S.M. Kharit

    2009-01-01

    Full Text Available The article is dedicated to the actual problem of modern health care — pneumococcal infections and opportunities of its prophylaxis. Authors describe risk groups of development of invasive pneumococcal infections. A characteristics of available at the present times in Russia and all over the world vaccines, including pneumococcal 7-valent vaccine (PCV7 Prevenar, intended to the prophylaxis of pneumococcal infections in children under the age 2 months — 5 years old. An experience of PCV7 use in the world in analyzed. The article gives an estimation of perspectives of inclusion of PCV7 to the national immunizations schedule.Key words: children, pneumococcal infections, prophylaxis, pneumococcal conjugated 7-valent vaccine.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2009;8(5:62-69

  8. DENGUE VACCINES.

    Science.gov (United States)

    Thisyakorn, Usa; Thisyakorn, Chule

    2015-01-01

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

  9. Adjuvants for Vaccines to Drugs of Abuse and Addiction

    OpenAIRE

    Alving, Carl R.; Matyas, Gary R.; Torres, Oscar; Jalah, Rashmi; Beck, Zoltan

    2014-01-01

    Immunotherapeutic vaccines to drugs of abuse, including nicotine, cocaine, heroin, oxycodone, methamphetamine, and others are being developed. The theoretical basis of such vaccines is to induce antibodies that sequester the drug in the blood in the form of antibody-bound drug that cannot cross the blood brain barrier, thereby preventing psychoactive effects. Because the drugs are haptens a successful vaccine relies on development of appropriate hapten-protein carrier conjugates. However, bec...

  10. Implications of plant glycans in the development of innovative vaccines.

    Science.gov (United States)

    Rosales-Mendoza, Sergio; Salazar-González, Jorge A; Decker, Eva L; Reski, Ralf

    2016-07-01

    Plant glycans play a central role in vaccinology: they can serve as adjuvants and/or delivery vehicles or backbones for the synthesis of conjugated vaccines. In addition, genetic engineering is leading to the development of platforms for the production of novel polysaccharides in plant cells, an approach with relevant implications for the design of new types of vaccines. This review contains an updated outlook on this topic and provides key perspectives including a discussion on how the molecular pharming field can be linked to the production of innovative glycan-based and conjugate vaccines.

  11. Qualidade conjugal: mapeando conceitos

    Directory of Open Access Journals (Sweden)

    Clarisse Mosmann

    2006-12-01

    Full Text Available Apesar da ampla utilização do conceito de qualidade conjugal, identifica-se falta de clareza conceitual acerca das variáveis que o compõem. Esse artigo apresenta revisão da literatura na área com o objetivo de mapear o conceito de qualidade conjugal. Foram analisadas sete principais teorias sobre o tema: Troca Social, Comportamental, Apego, Teoria da Crise, Interacionismo Simbólico. Pelos postulados propostos nas diferentes teorias, podem-se identificar três grupos de variáveis fundamentais na definição da qualidade conjugal: recursos pessoais dos cônjuges, contexto de inserção do casal e processos adaptativos. Neste sentido, a qualidade conjugal é resultado do processo dinâmico e interativo do casal, razão deste caráter multidimensional.

  12. Polymers for Protein Conjugation

    Directory of Open Access Journals (Sweden)

    Gianfranco Pasut

    2014-01-01

    Full Text Available Polyethylene glycol (PEG at the moment is considered the leading polymer for protein conjugation in view of its unique properties, as well as to its low toxicity in humans, qualities which have been confirmed by its extensive use in clinical practice. Other polymers that are safe, biodegradable and custom-designed have, nevertheless, also been investigated as potential candidates for protein conjugation. This review will focus on natural polymers and synthetic linear polymers that have been used for protein delivery and the results associated with their use. Genetic fusion approaches for the preparation of protein-polypeptide conjugates will be also reviewed and compared with the best known chemical conjugation ones.

  13. Immunogenicity and Efficacy of Different Haemophilus influenzae type b Vaccines

    Directory of Open Access Journals (Sweden)

    Mojgani, N.

    2014-11-01

    Full Text Available Haemophilus influenzae, a major cause of meningitis in young children leading to death and other neurological sequelae. The disease leaves 15 to 35% of the survivors with permanent disabilities, such as, mental retardation or deafness. Despite the availability of new and more powerful antibiotics children with Hib meningitis still suffer from high mortality or morbidity. The emergence of multiresistant Hib strains causes increasing difficulties in selecting proper antibiotics for the treatment. Since 1970, the capsular polysaccharide polyribosylribitol phosphate (PRP in H. influenzae b has been the target for vaccine development. The first Hib polysaccharide vaccine licensed in 1985, proved immunogenic in human adults, but failed to elicit an immune response in children under 2 years of age who were at greatest risk of developing the invasive Hib infection. These factors led to one of the most exciting advances in pediatrics, the development of Hib conjugate vaccines. Unlike most other vaccines for preventing a particular disease which are generally similar for all types, the specific characteristics of the available Hib conjugate vaccines licensed vary from each other in structure and immunological properties. In this review the immunogenicity and efficacy of Hib vaccines including a PRP vaccine; b Conjugate vaccines; and c Combination vaccines is evaluated.

  14. Rabies Vaccine

    Science.gov (United States)

    ... high risk of exposure to rabies, such as veterinarians, animal handlers, rabies laboratory workers, spelunkers, and rabies biologics production workers should be offered rabies vaccine. The vaccine should also be considered for: (1) ...

  15. Edible vaccines.

    OpenAIRE

    Artnzen, C J

    1997-01-01

    Vaccines were the result of trial and error research until molecular biology and genetic engineering made possible the creation of of many new and improved vaccines. New vaccines need to be inexpensive, easily administered, and capable of being stored and transported without refrigeration; without these characteristics, developing countries find it difficult to adopt vaccination as the central strategy for preventing their most devastating diseases. The authors describe a promising approach t...

  16. Periodontal vaccine

    OpenAIRE

    Ranjan Malhotra; Anoop Kapoor; Vishakha Grover; Aaswin Kaur Tuli

    2011-01-01

    Vaccine is the name applied generally to a substance of the nature of dead or attenuated living infectious material introduced into the body with the object of increasing its power to resist or get rid of a disease. Vaccines are generally prophylactic, i.e. they ameliorate the effects of future infection. One such vaccine considered here is the "Periodontal vaccine". Till date, no preventive modality exists for periodontal disease and treatment rendered is palliative. Thus, availability of pe...

  17. HPV Vaccine

    Science.gov (United States)

    ... Surgery? A Week of Healthy Breakfasts Shyness HPV Vaccine KidsHealth > For Teens > HPV Vaccine Print A A A What's in this article? ... 11 or 12 through age 21 If needed, kids can get the vaccine starting at age 9. continue How Does the ...

  18. Antibody persistence for up to 5 years after a fourth dose of Haemophilus influenzae type b and Neisseria meningitidis serogroups C and Y-tetanus toxoid conjugate vaccine (HibMenCY-TT) given at 12-15 months of age.

    Science.gov (United States)

    Marshall, Gary S; Blatter, Mark; Marchant, Colin; Aris, Emmanuel; Mesaros, Narcisa; Miller, Jacqueline M

    2013-06-01

    A 4-dose series of recently licensed Haemophilus influenzae type b-meningococcal serogroups C and Y-tetanus toxoid conjugate vaccine (HibMenCY-TT) was immunogenic with a clinically acceptable safety profile in infants, with antibodies persisting in most participants for 1 year following dose 4. This study assessed antibody persistence up to 5 years after vaccination. Participants had received HibMenCY-TT or Hib-TT at 2, 4 and 6 months of age. At age 12-15 months, HibMenCY-TT vaccinees received a fourth HibMenCY-TT dose (HibMenCY x 4 group), whereas those who received Hib-TT received a fourth dose of either Hib-TT (Hib) or HibMenCY-TT (HibMenCY x 1). Blood samples were collected 1 month and 1, 3 and 5 years after the last dose for measurement of antipolyribosylribitol phosphate (the Hib capsular po