Peripheral CD4 T follicular cells induced by a conjugated pneumococcal vaccine correlate with enhanced opsonophagocytic antibody responses in younger individuals

Abstract

Background: PCV13 (conjugated polysaccharide) and PPSV23 (polysaccharide only) are two licensed vaccines targeting S. pneumoniae. The role of CD4 T-cell responses in pneumococcal vaccines among healthy participants and their impact on antibodies is not yet known.

Methods: Ten adults (5 old and 5 young) received PCV13 (prime) and a year later PPSV23 (boost). Blood samples were collected prior to and multiple time points after vaccination. CD4 T cells responding to CRM₁₉₇, polysaccharide (PS), CRM₁₉₇ conjugated polysaccharide (CPS), PCV13 and PPSV23 vaccines were measured by flow cytometry. Serum antibodies were analyzed via multiplex opsonophagocytosis (MOPA) and pneumococcal IgG assays.

Results: Vaccine-specific CD4 T cells were induced in all ten vaccinees post PCV13. Older vaccinees mounted higher peak responses and those specific for PCV13 and conjugated PS-1 were more polyfunctional compared to the younger group. Vaccine-elicited peripheral T follicular helper (Tfh) cells were only detected in the younger group who also exhibited a higher fold change in OPA titers post both vaccines. Importantly, Tfh cells following PCV13 correlated only with PCV13 serotype specific OPA titers after PPSV23 vaccination.

Conclusions: These findings demonstrate age related differences in immune response and the potential importance of Tfh in modulating functional antibody responses following pneumococcal vaccination.

Keywords: (3–10): PCV13; CD4 T cells; Glycoconjugate and CRM(197); Opsonophagocytic antibodies; PPSV23; Pneumococcal antibodies; Polysaccharide; Proliferation; T follicular helper cells.