Abstract and Introduction
Abstract
Background Pneumococcal conjugate vaccine (PCV) induces protective anticapsular IgG, which mediates disease immunity. IgG persistence may influence long-term protection.
Methods An observational, prospective, longitudinal study of nasopharyngeal carriage among American Indian households from 2006 to 2008 evaluated long-term immunogenicity of 7-valent PCV (PCV7). Children unimmunized with PCV were age-matched to those PCV7 immunized at least 4 years prior (ratio 1:3 or 1:4). Blood collected at the final study visit was analyzed for PCV7 serotype IgG (enzyme-linked immunosorbent assay) and for functional activity (multiplex-opsonophagocytic assay) for serotypes 4, 6B, 14 and 23F. Geometric mean concentrations (GMCs), titers (GMTs) and the odds of serotype-specific IgG ≥0.35 μg/mL were compared according to immunization status using a matched regression approach.
Results Eight unimmunized and 28 immunized children age-matched at the time of serum collection (mean age: 7.9 years) were included. Serotype-specific GMCs, GMTs and proportions above the correlate of protection did not differ between the groups except for serotypes 14 and 23F. Serotype 14 GMCs (immunized 0.7 vs. unimmunized 0.2; P = 0.02) and serotype 23F GMTs (immunized 388.3 vs. unimmunized 47.8; P = 0.03) were significantly higher among immunized children. IgG concentrations and functional titers among immunized children were strongly correlated for serotypes 4 (r = 0.78; P ≤ 0.001) and 14 (r = 0.52; P ≤ 0.01).
Conclusions PCV serotype-specific IgG concentrations 4 years following PCV vaccination do not persist above natural levels for most serotypes. Exposure to pneumococcus may be critical in maintaining persistent serotype-specific IgG; the elimination of circulating vaccine type pneumococci by PCV may have effects on long-term immunity.
Introduction
The 7-valent pneumococcal conjugate vaccine (PCV7, Pfizer, Pearl River, NY; serotypes 4, 6B, 9V, 14, 18C, 19F and 23F) was licensed and introduced into the US infant immunization schedule in 2000 with the primary series given at 2, 4 and 6 months and a booster dose at 12–15 months of age (ie, 3 + 1 schedule). Direct and indirect protection against vaccine serotype invasive disease and colonization was documented, including among high-risk populations. In 2010, PCV7 was replaced with a 13-valent product (PCV13, Pfizer) adding serotypes 1, 3, 5, 6A, 7F and 19A. Although studies have demonstrated that PCVs generate a substantial immune response, limited data exist on the longevity of the response during routine PCV use when vaccine serotype colonization is virtually eliminated and replacement colonization with nonvaccine serotypes has occurred.
Using pooled data from 3 PCV efficacy trials, 0.35 μg/mL was established as the IgG concentration that predicted vaccine efficacy against invasive pneumococcal disease and is accepted by regulatory authorities as the evaluation threshold for licensure of new PCVs. Most studies measure the IgG response following completion of the primary series or immediately following the booster dose; several have evaluated the long-term IgG levels in the context of an efficacy trial, but none to our knowledge in the context of routine PCV use. Translating the 0.35 μg/mL correlate to contextualize the likelihood of IgG yielding protection years following the initial immunization series is poorly understood. The objective of this analysis was to measure serotype-specific pneumococcal IgG concentrations in children who were immunized with PCV7 at least 4 years before determining IgG persistence in a setting where vaccine serotype strains are no longer circulating.