Divergent Memory B Cell Responses in a Mixed Infant Pneumococcal Conjugate Vaccine Schedule

Abstract

Background: Vaccine-induced immunity against pneumococcal infection relies on the generation of high concentrations of antibody and B cell memory. Both the 10-and the 13-valent pneumococcal conjugate vaccines (PCV10 and PCV-13) effectively reduce disease caused by vaccine serotypes. It is unknown whether the generation of B cell memory requires several doses of the same vaccine or whether different PCVs are interchangeable. Methods: Children in the United Kingdom (n=178) who had previously received PCV-13 at 2 and 4 months were randomized 1: 1 to receive a PCV13 or PCV-10 booster at age 12 months. Peripheral blood memory B cells (B MEM) were quantified before and at 1 and 12 months after vaccination using a cultured enzyme-linked immunospot assay for pneumococcal serotypes 1, 3, 4, 9V, 14, 19A, and diphtheria and tetanus toxoid. Correlations between B MEM frequencies and simultaneously measured antibody (IgG and opsonophagocytic assay) was also assessed. Results: A significant rise in postbooster B MEM frequency was seen for 5 out of 6 serotypes in the PCV-13 group and none in the PCV-10 group. In the PCV-13 group, there was a particularly large increase in serotype 3-specific B MEM associated with only a small increase in antibody. Postbooster B MEM responses correlated positively with antibody, but correlations between prebooster B MEM and subsequent B MEM and antibody responses were inconsistent. Conclusions: After priming with PCV-13 in early infancy, a booster dose of PCV-10 does not induce detectable peripheral blood B MEM responses but a PCV-13 booster does induce robust responses. Booster responses to PCVs may be dependent on homologous carrier protein priming.