Intranasal Immunization with the Commensal Streptococcus mitis Confers Protective Immunity against Pneumococcal Lung Infection

Streptococcus pneumoniae causes various diseases worldwide. Current pneumococcal vaccines protect against a limited number of more than 90 pneumococcal serotypes, accentuating the urgent need to develop novel prophylactic strategies.S. pneumoniae and the commensalStreptococcus mitis share immunogenic characteristics that makeS. mitis an attractive vaccine candidate againstS. pneumoniae . In this study, we evaluated the potential ofS. mitis and its mutant expressing pneumococcal capsule type 4 (S. mitis TIGR4cps) to induce protection againstS. pneumoniae lung infection in mice. Our findings show that intranasal vaccination withS. mitis protects againstS. pneumoniae strains D39 (serotype 2) and TIGR4 (serotype 4) in a serotype-independent fashion, which is associated with enhanced antibody and T cell responses. Furthermore,S. mitis TIGR4cps conferred additional protection againstS. pneumoniae TIGR4, but not against D39. The findings highlight the potential ofS. mitis to generate protection that combines both serotype-independent and serotype-specific responses.