Herd immunity and pneumococcal conjugate vaccine: a quantitative model.

Department of Biostatistics, Rollins School of Public Health, Emory University, Atlanta, GA 30322, USA.
Vaccine (Impact Factor: 3.49). 08/2007; 25(29):5390-8. DOI: 10.1016/j.vaccine.2007.04.088
Source: PubMed

ABSTRACT 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 serotypes, in particular 19A, were noted in most unvaccinated age groups, but these increases were substantially smaller than the concurrent decreases among the vaccine serotypes. Also, the model estimated PCV7 to have a greater (p=0.014) indirect impact on the incidence of invasive pneumococcal disease caused by all vaccine serotypes among African-Americans of all ages than for whites. Thus, conjugate vaccines may be able to induce herd effects even in situations where vaccine coverage is far from complete or with schedules using fewer than 3 or 4 doses. Because the model was based on incidence rates and PCV7 coverage in Atlanta, our findings should be validated in other geographic areas.

  • [Show abstract] [Hide abstract]
    ABSTRACT: The immunogenicity of polysaccharides as human vaccines was enhanced by coupling to protein carriers. Conjugation transformed the T cell-independent polysaccharide vaccines of the past to T cell-dependent antigenic vaccines that were much more immunogenic and launched a renaissance in vaccinology. This review discusses the conjugate vaccines for prevention of infections caused by Hemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis. Specifically, the characteristics of the proteins used in the construction of the vaccines including CRM, tetanus toxoid, diphtheria toxoid, Neisseria meningitidis outer membrane complex, and Hemophilus influenzae protein D are discussed. The studies that established differences among and key features of conjugate vaccines including immunologic memory induction, reduction of nasopharyngeal colonization and herd immunity, and antibody avidity and avidity maturation are presented. Studies of dose, schedule, response to boosters, of single protein carriers with single and multiple polysaccharides, of multiple protein carriers with multiple polysaccharides and conjugate vaccines administered concurrently with other vaccines are discussed along with undesirable consequences of conjugate vaccines. The clear benefits of conjugate vaccines in improving the protective responses of the immature immune systems of young infants and the senescent immune systems of the elderly have been made clear and opened the way to development of additional vaccines using this technology for future vaccine products.
    Human vaccines & immunotherapeutics. 08/2013; 9(12).
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The standard opsonization phagocytosis and killing assay (OPKA) for antibodies to pneumococcal capsular polysaccharide was modified to permit evaluation of protection-mediating antibodies to pneumococcal surface protein A (PspA). We found that by increasing the incubation time with complement and phagocytes from 45 min to 75 minutes that the protective activity could be readily detected. In another modification we used a capsule type 2 target strain that expressed PspA but not pneumococcal surface protein C (PspC). Using these modifications separately or in combination, rabbit antisera to recombinant α-helical or proline-rich domains of PspA mediated > 50% killing of the target strain. The ability of normal human sera to mediate killing of pneumococci in this modified OPKA correlated with their levels of antibody to PspA and their ability to protect mice against fatal infection with a type 3 strain. Passive protection of mice against pneumococci and killing in the modified OPKA were both lost when normal human serum was adsorbed with rPspA on Sepharose, thus supporting the potential utility of the modified OPKA to detect protective antibody to PspA. In the standard OPKA, monoclonal antibody to PspA was strongly protective in the presence of sub-protective amounts of anti-capsule. Thus, the currently established high-throughput OPKA for antibody to capsule could be modified in either of two ways to permit evaluation of opsonic efficacy of antibodies to PspA.
    Clinical and vaccine Immunology: CVI 08/2013; · 2.37 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background. About 10% of pediatric patients with invasive pneumococcal disease (IPD) die from the disease. Some primary immunodeficiencies (PIDs) are known to confer predisposition to IPD. However, a systematic search for these PIDs has never been carried out in children presenting with IPD. Methods. We prospectively collected pediatric cases of IPD requiring hospitalization, between 2005 and 2011, in 28 pediatric wards throughout France. IPD was defined as a positive pneumococcal culture, PCR result and/or soluble antigen detection at a normally sterile site. The immunological assessment included abdominal ultrasound, whole-blood counts and smears, determinations of plasma Ig and complement levels, and the evaluation of pro-inflammatory cytokines. Results. We included a total of 163 children with IPD (M/F sex ratio: 1.3, median age: 13 months). Seventeen children had recurrent IPD. Meningitis was the most frequent type of infection (87%), others were pleuropneumonitis, isolated bloodstream infection, osteomyelitis, endocarditis and mastoiditis. One patient with recurrent meningitis had a congenital cerebrospinal fluid fistula. The results of immunological explorations were abnormal in 26 children (16%) and a PID was identified in 17 patients (10%), including one case of MyD88 deficiency, three of complement fraction C2 or C3 deficiencies, one of isolated congenital asplenia and two of Bruton's agammaglobulinemia. The proportion of PIDs was much higher in children older than two years than in younger children (26% vs 2%, p<0.001). Conclusions. Children with IPD should undergo immunological investigations, particularly those older than two years, as PIDs may be discovered in up to 26% of cases.
    Clinical Infectious Diseases 04/2014; · 9.42 Impact Factor

Full-text (2 Sources)

Available from
Jun 3, 2014