Systems Analysis of Immunity to Pneumococcal Vaccination in Preterm and Full-term Infants

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Abstract
Background: Preterm infants mount lower humoral responses to the 13-valent pneumococcal conjugate vaccine (PCV13) than full-term infants; however, the long-term impact of prematurity on vaccine-induced protection remains unclear. This study investigates the innate and adaptive immune responses to PCV13 in preterm versus full-term infants. Methods: Thirty-eight infants (19 preterm, 19 full-term) received PCV13 at 2, 4, 6, and 12 months. Polysaccharide-specific memory B cells (MBCs) were enumerated and phenotyped by flow cytometry, while PS-specific IgG concentrations were measured by ELISA before and after the third and booster doses. RNA sequencing was performed before and 3 days after the third dose. Results: Primary immunization induced a markedly broader, predominantly proinflammatory transcriptional response in preterm infants. Preterm infants exhibited higher frequencies of total and PS-specific extragerminal center (GC) MBCs but lower switched MBCs following primary immunization; these differences largely converged postbooster. Polysaccharide-specific IgG titers remained generally lower in preterm infants. Polysaccharide-specific switched MBCs postprimary correlated positively with antibody titers postbooster. The broad upregulation of proinflammatory genes in preterm infants was negatively correlated with antibody concentrations. Conclusions: PCV13 immunization elicits distinct immunological profiles in preterm versus full-term infants. Booster immunization largely harmonized MBC composition across gestational groups, while early GC-derived MBC populations emerged as candidate correlates of durable immunity.

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