Cross-reactive immunity within pneumococcal serogroups: Implications for next-generation vaccine development.

OBJECTIVES

This study aims to investigate within-serogroup cross-reactive immunity among pneumococcal serotypes using inhibition opsonophagocytic assays (OPA). The findings provide immunologic insights into serotype-replacement dynamics with implications for the design of future pneumococcal vaccines.

METHODS

Pooled sera were prepared from 24 adults aged ≥40 years: Pool 1 (PCV13/PPSV23 recipients), Pool 2 (PCV20 recipients), and Pool 3 (PCV21 recipients). Cross-reactivity was examined across five major serogroups (6, 9, 15, 19, 23) by measuring residual OPA titers after adsorption with homologous or heterologous inactivated pneumococcal strain.

RESULTS

Cross-reactivity varied by serogroup. In serogroup 6, 6A induced broad cross-protection against 6B and 6C, whereas 6D showed only homologous reactivity. In serogroup 15, inhibition OPA revealed inconsistent cross-reactivity between serotypes 15B and 15C, with only limited cross-reactivity observed for 15A. Pooled sera from PCV21 recipients (containing 15A and 15C) demonstrated pronounced heterologous inhibition toward 15B. In serogroup 19, cross-reactivity between 19A and 19F was partial and asymmetric. Heterologous adsorption showed negligible reductions in OPA titers for serogroups 9 and 23.

CONCLUSIONS

The inhibition OPA enabled a precise assessment of serogroup-level cross-reactive immunity, revealing heterogeneous patterns of cross-reactivity. These findings underscore the need for careful serotype selection and epitope evaluation in next-generation vaccine formulations.