Pneumococcal Serotype-Specific Antibodies Persist through Early Childhood after Infant Immunization: Follow-Up from a Randomized Controlled Trial

Abstract

BackgroundIn a previous UK multi-center randomized study 278 children received three doses of 7-valent (PCV-7) or 13-valent (PCV-13) pneumococcal conjugate vaccine at 2, 4 and 12 months of age. At 13 months of age, most of these children had pneumococcal serotype-specific IgG concentrations ≥0.35 µg/ml and opsonophagocytic assay (OPA) titers ≥8.MethodsChildren who had participated in the original study were enrolled again at 3.5 years of age. Persistence of immunity following infant immunization with either PCV-7 or PCV-13 and the immune response to a PCV-13 booster at pre-school age were investigated.ResultsIn total, 108 children were followed-up to the age of 3.5 years and received a PCV-13 booster at this age. At least 76% of children who received PCV-7 or PCV-13 in infancy retained serotype-specific IgG concentrations ≥0.35 µg/ml against each of 5/7 shared serotypes. For serotypes 4 and 18C, persistence was lower at 22–42%. At least 71% of PCV-13 group participants had IgG concentrations ≥0.35 µg/ml against each of 4/6 of the additional PCV-13 serotypes; for serotypes 1 and 3 this proportion was 45% and 52%. In the PCV-7 group these percentages were significantly lower for serotypes 1, 5 and 7F. A pre-school PCV-13 booster was highly immunogenic and resulted in low rates of local and systemic adverse effects.ConclusionDespite some decline in antibody from 13 months of age, these data suggest that a majority of pre-school children maintain protective serotype-specific antibody concentrations following conjugate vaccination at 2, 4 and 12 months of age.Trial Registration ClinicalTrials.gov NCT01095471

Persistence of immunity in children immunised with 13-valent pneumococcal conjugate vaccine and impact on nasopharyngeal carriage: a cross-sectional study

“…Long-term immunogenicity studies on CRM 197 -based PCVs have been largely based on PCV7, indicating that serum IgG levels against vaccine serotypes remained ≥0.35 µg/mL in the majority of children for at least 4 years after the booster. 5 6 In this study, trend lines predicted that IgG titres against the predominant nasopharyngeal isolates in 2010–2014 (19A and 19F) in this region could persist above 0.35 µg/mL for >10 years in both the 2+1 and 3+1 immunisation groups, but the antibody concentrations and the persistence for the rare serotype 7F were lower (<3 years) in both groups.…”

“… 7 Some clinical trials of PCVs also observed a robust immune response to one dose of PCV13 in previously immunised children aged 2–5 years. 5 8 …”

The Efficacy and Duration of Protection of Pneumococcal Conjugate Vaccines Against Nasopharyngeal Carriage

“…The polysaccharide capsule of 19F is more resistant to complement deposition than 6B and requires higher levels of antibodies for opsonophagocytosis. 38 However, although trials 37,40,41 have shown persistence of serum antibodies several years after vaccination, the exact mechanism underlying the protection against acquisition of carriage remains unclear. Such mechanisms could perhaps involve mucosal immunological responses 42 in addition to preexisting circulating serum immunoglobulin (IgG), with serological markers incompletely capturing the mucosal response.…”

The Antibody Response Following a Booster With Either a 10- or 13-valent Pneumococcal Conjugate Vaccine in Toddlers Primed With a 13-valent Pneumococcal Conjugate Vaccine in Early Infancy

“…IgG levels and OPA titers at 24 months were largely determined by the amount of antibody detected 1 month post booster at 13 months of age, which has been previously demonstrated where the same PCV was used for both priming and boosting. 24 These findings suggest that boosting with a different vaccine containing the same capsular serotypes, albeit conjugated to different carrier proteins, induces an immune response that is not only driven by short-lived extrafollicular B cells but also the generation of long-lived plasma cells, a hallmark of immune memory.…”