Predictors of Pneumococcal Conjugate Vaccine Immunogenicity among Infants and Toddlers in an American Indian PnCRM7 Efficacy Trial

Abstract

Background. Pneumococcal conjugate vaccines are important for the prevention of serious illness and death among infants. Factors associated with pneumococcal conjugate vaccine immunogenicity have not been explored.Methods. Children !24 months of age received 2, 3, or 4 doses of 7-valent pneumococcal conjugate vaccine (PnCRM7) or control vaccine depending on age at enrollment. Serum samples were tested for serotype-specific antibodies by enzyme-linked immunosorbant assay. Multiple linear regression was used to determine predictors of immunogenicity.Results. Among 315 PnCRM7-vaccinated subjects and 295 control subjects enrolled at !7 months of age, geometric mean concentrations (GMCs) of antibodies were significantly higher after dose 3 than after dose 2 for all serotypes except type 4. The proportion of subjects with antibody concentrations у5.0 mg/mL was higher for all serotypes, but the proportion with concentrations у0.35 mg/mL was higher only for types 6B and 23F. Threedose and 2-dose regimens for those 7-11 and 12-23 months of age, respectively, were highly immunogenic. Increased maternal antibody concentrations were associated with reduced responses to dose 1 and 3 but not to dose 4 of PnCRM7.Conclusions. Maternal antibody is associated with a reduced infant response to PnCRM7 but does not interfere with immune memory. In infants, a third priming dose increases the antibody GMC and the proportion achieving an antibody concentration у5.0 mg/mL but has little impact on the proportion achieving a concentration у0.35 mg/mL.

Comparative Immunogenicity of 7 and 13-Valent Pneumococcal Conjugate Vaccines and the Development of Functional Antibodies to Cross-Reactive Serotypes

“…This observation is supported in our study by the higher 19F OPA titers in PCV13 recipients when matched on 19F IgG concentrations and suggests that PCV13 may confer enhanced protection from 19F disease over and above that seen in the PCV7 era. Encouragingly, our results also show that for the seven common serotypes in both vaccines, IgG concentrations were similar compared to previous studies among various populations that have been studied including the same population of American Indian children [18], other children in the United States [19], [20] and other developed [21], [22] and developing countries [23], [24].…”

Age-Stratified Prevalences of Pneumococcal-Serotype-Specific Immunoglobulin G in England and Their Relationship to the Serotype-Specific Incidence of Invasive Pneumococcal Disease Prior to the Introduction of the Pneumococcal 7-Valent Conjugate Vaccine

“…The data generated for serotype-specific IgG concentrations in young infants are comparable to those of previous studies (2,19,26,32,35). However, they are lower than the antibody levels reported from pneumococcal vaccine studies in England (13) and studies of American Indian infants (28), which may be accounted for by differences in assay procedures or the carriage rates of the population.…”

Immunogenicity, Impact on Carriage and Reactogenicity of 10-Valent Pneumococcal Non-Typeable Haemophilus influenzae Protein D Conjugate Vaccine in Kenyan Children Aged 1–4 Years: A Randomized Controlled Trial

“…Although the serotype-specific antibody concentrations in this study were lower than observed following 1 or 2 doses of 9-valent PCV in UK toddlers, the proportions achieving the threshold of ≥0.35 mcg/mL for each serotype were comparable [32]. Antibody GMCs following one dose of vaccine in 12–23 month olds in our study appear similar to those observed in American Indian children vaccinated with 7-valent PCV for serotypes 6B, 9V, and 14; however, GMCs were higher in our study for serotypes 4, 18C and 19F and lower for serotype 23F [33].…”