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

Abstract

BackgroundProtection against disease or colonization from serotypes related to those in pneumococcal conjugate vaccines (i.e. cross-protection) vary by serotype; the basis for this variation is not understood. The 13-valent pneumococcal conjugate vaccine (PCV13) replaced 7-valent conjugate (PCV7) in the USA in 2010 allowing assessment of PCV7 and PCV13 immunogenicity and functional cross-protection in vitro.MethodsPost-primary, pre-booster and post-booster sera from American Indian children receiving exclusively PCV7 or PCV13 were collected. IgG was measured by ELISA for 13 vaccine serotypes; functional antibody was assessed by opsonophagocytic killing assays for serotypes 6A/B/C and 19A/F.ResultsPost-primary IgG geometric mean concentrations (GMC) for serotypes 4 and 9V were lower in PCV13 recipients while 19F GMCs were higher. Only 19F differences persisted after receipt of the booster dose. Functional antibody activity was higher among PCV13 recipients for 6A, 6C, 19A and 19F (p<0.04), and among PCV7 recipients for 6B (p = 0.01). Following PCV7, functional antibodies to 6A but not 19A were observed. High levels of 6C functional activity were seen after PCV13 but not PCV7.ConclusionsFunctional antibody activity against 6A/B/C and 19A/F suggest that PCV13 is likely to control the 19A disease and 6C disease remaining despite widespread use of PCV7.

Schedules for Pneumococcal Vaccination of Preterm Infants: An RCT

“…4,21 However, compared with previous term (PCV13) and preterm (PCV7) studies, antibody concentrations after primary and booster vaccination are lower overall, resulting in lower seroprotection after primary vaccination. 4,5,8,9,22 Similarly, compared with the recent PCV13 preterm study, 7 lower IgG GMCs and seroprotection rates were seen for all serotypes. These differences may be due to the different laboratory testing methods used for serotype-specific antibody concentrations, but potential biological explanations include interactions with concurrently administered vaccines, the younger gestation of the study cohort, or our broad inclusion criteria encompassing infants with complex medical problems (representative of the preterm population).…”

“…1 -3 In most industrialized countries with established pneumococcal immunization programs, the 13-valent pneumococcal conjugate vaccine (PCV13) has superseded the 7-valent pneumococcal conjugate vaccine (PCV7) and has been shown to be highly immunogenic in term infants. [4][5][6] The immunogenicity of PCV13 in premature infants receiving a 2-3-4 and 12-month schedule was only recently reported and revealed lower immunoglobulin G (IgG) concentrations for 8 serotypes after both primary and booster doses compared with term infants. 7 This lower immunogenicity is consistent with previous PCV7 studies 8 -10 and is concerning because premature infants are also less likely to benefit from the protective maternal antibodies transferred during late pregnancy.…”

Pneumococcal carriage in young children after introduction of PCV13 in Hong Kong

“…Serotype 6C has been reported to be disease causing with an increase in prevalence of IPD caused by 6C in the post PCV era [32][33][34][35]. Serotypes 6A and 6C are structurally similar with in-vitro immunological crossreactivity, the inclusion of 6A in the PCV13 has been reported to induce cross-functional anti-6C opsonophagocytic responses [36][37][38]. However, the prevalence of 6C in carriage isolates as well as increasingly reported IPD caused by 6C in the post PCV13 era raises the concern whether PCV13 can provide adequate protection against 6C.…”

Interchangeability of meningococcal group C conjugate vaccines with different carrier proteins in the United Kingdom infant immunisation schedule

“…Hib polyribosylribitol phosphate (PRP), diphtheria, tetanus and PT IgG were quantified using validated ELISAs, based on previously described assays [12][13][14][15]. Serotype-specific pneumococcal antibodies were measured as described previously [16].…”