Immunogenicity and Immunological Memory Induced by the 13-Valent Pneumococcal Conjugate Followed by the 23-Valent Polysaccharide Vaccine in HIV-Infected Adults

Background. Vaccine-induced memory B-cell (MBC) subsets have distinct roles in the establishment of protective immunity; MBCs expressing nonswitched immunoglobulin M (IgM(+) MBCs) replenish the MBC pool, whereas MBCs expressing isotype-switched immunoglobulin (sIg(+) MBCs) differentiate into plasma cells upon antigen reencounter. We investigated immunogenicity and MBCs induced by combined 13-valent pneumococcal conjugate vaccine (PCV13) and 23-valent pneumococcal polysaccharide vaccine (PPV23) in human immunodeficiency virus (HIV)-infected adults. Methods. Forty HIV-seropositive adults receiving ART with undetectable viral loads were enrolled. Seventeen had a CD4(+) T-cell count of >= 400 cells/mu L (group A), and 23 had a CD4(+) T-cell count of 200-399 cells/mu L (group B). All adults received PCV13 and, 1 year later, PPV23. Levels of IgM(+)MBCs (defined as polysaccharide [PS]-specific CD19(+)CD10(-)CD27(+)CD21(++)IgM(+)MBCs) and sIg(+)MBCs (defined as PS-specific CD19(+)CD10(-)CD27(+)CD21(++)IgM(-)MBCs) and antibodies against PS14 and PS3 were measured prior and 1 month after each vaccination. Results. Immunization caused a significant increase in PS antibodies, compared with levels at baseline (P < .001). Group B achieved significantly lower titers than group A (P < .05 for both PS14 and PS3). After receipt of PCV13, levels of IgM(+) MBCs were unchanged, whereas levels of sIg(+) MBCs increased significantly (P < .05 for PS14 and P < .001 for PS3). In contrast, following PPV23 receipt, levels of IgM(+) MBCs were significantly reduced, and levels of sIg(+) MBCs remained stable. A positive correlation was observed between baseline IgM(+) and sIg(+) MBC counts 1 month after PCV13 receipt but not after PPV23 receipt. Conclusions. PPV23 receipt 12 months after PCV13 receipt improved PCV13 immunogenicity. The reduction in the IgM(+) MBC count observed after PPV23 receipt suggests that PPV23 has a depleting effect on PCV13-associated immunological memory.