Pneumococcal capsular polysaccharide vaccine-mediated protection against serotype 3 Streptococcus pneumoniae in immunodeficient mice

Pneumococcal capsular polysaccharide (PPS) vaccines are less immunogenic in immunocompromised than immunocompetent individuals. However, neither the efficacy of PPS vaccines in immunocompromised individuals nor the host cellular subsets required for vaccine efficacy against pneumococcal disease have been directly investigated. In this study, we vaccinated CD4-deicient (CD4 ^-/-), CD8-deficient (CB8^-/-), and secretory immunoglobulin M-deficient (sIgM^-/-) mice and wild-type C57BL/6 (Wt) mice with a conjugate of PPS of serotype 3 and tetanus toxoid (PPS3-TT) and determined the antibody response and efficacy of vaccination against systemic and pulmonary challenge with serotype 3 pneumococcus in immunized and control mice. Our results showed that the isotype and predominant IgG subclass of the PPS3 response differed between immunodeficient mouse strains and between immunodeficient and Wt mice, with CB8^-/- mice having the most robust response. Vaccination protected Wt, CB4^-/-, and sIgM^-/- mice from death resulting from both systemic and pulmonary challenge, whereas CB8^-/- mice were protected only from systemic and not from pulmonary challenge. Passive vaccination with PPS3-TT-induced sera from Wt, CB4 ^-/-, CD8^-/-, and sIgM^-/- mice protected naïve Wt mice from death due to pulmonary challenge; however, CB8 ^-/- mice were not protected by sera from Wt or CB8^-/- mice. Our findings suggest that PPS-based vaccines can be effective in the setting of CD4 T-cell deficiency but that CD8 T cells could be required for vaccine-mediated protection against pulmonary challenge with serotype 3 pneumococcus.