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O011 - ESTABLISHMENT OF SEROTYPE-SPECIFIC IMMUNOLOGICAL MEMORY BY DIFFERENT INFANT IMMUNIZATION SCHEDULES WITH PCV13 (ID 498)
Abstract
Background
Vaccine-induced memory B cell(MBC) composition is important for vaccine effectiveness, since different MBC subsets have distinct roles in the duration and magnitude of protection. Here, we compare the immunogenicity and phenotype of immunological memory induced by the three commonly used PCV13 infant immunisation schedules (3+0,2+1,3+1).
Methods
Thirty infants(aged 2-15 months) were stratified into 3 groups: 3+0(n=14), 2+1(n=7), 3+1(n=9). Peripheral Blood Monocyte Cells(PBMCs) and serum were collected before and 28days after the last dose of each schedule. Antibodies were assessed by ELISA. Pneumococcal serotype(PS)-specific IgM, switched Ig(swIg) and extra-germinal center(extra-GC) MBCs were enumerated with Flow Cytometry.
Results
All schedules yield protective antibody titers. Higher levels are achieved when the third dose is given as a booster [GMT(mg/dl) 3+0 vs 2+1: PS1 7.9 vs 19.5 p=.24, PS3 1.7 vs 3.8 p<.05, PS9V 13.6 vs 31.2 p=.12]. Regarding PS-specific MBC response to booster, 2-dose priming(2+1) leads to expansion of the swIg MBC pool (26% pre- vs 45% post-booster, p<.05), whereas 3-dose priming(3+1) to higher IgM MBCs (13% pre vs 29% post-booster,p=.28). PS-specific extra-GC MBCs in group 3+0 were higher after the last dose compared to the other groups [79% vs 46% (2+1) vs 54% (3+1),p<.05].
Conclusions
The number of primary doses affects the phenotype of produced MBCs, suggesting long-term effects on the induced protection as, upon antigen restimulation, IgM MBCs maintain the MBC pool whereas swIg MBCs differentiate into plasma cells. At six months of age (after 3+0 schedule), subjects were unable to establish GC-derived MBCs implying an age-related effect on germinal center formation following vaccination.