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

Streptococcus pneumoniae is a bacterial pathogen that causes various diseases of public health concern worldwide. Current pneumococcal vaccines target the capsular polysaccharide surrounding the cells. However, only up to 13 of more than 90 pneumococcal capsular serotypes are represented in the current conjugate vaccines. In this study, we used two experimental approaches to evaluate the potential of Streptococcus mitis , a commensal that exhibits immune cross-reactivity with S. pneumoniae , to confer protective immunity to S. pneumoniae lung infection in mice. Firstly, we assessed the immune response and protective effect of S. mitis wild type against lung infection by S. pneumoniae strains D39 (serotype 2) and TIGR4 (serotype 4). Secondly, we examined the ability of S. mitis mutant expressing the S. pneumoniae type 4 capsule ( S. mitis TIGR4cps) to elicit focused protection against S. pneumoniae TIGR4. Our results showed that intranasal immunization of mice with S. mitis displayed significantly higher levels of serum IgG and IgA antibodies reactive to both S. mitis and S. pneumoniae as well as an enhanced production of IL-17A, but not IFN-γ and IL-4, compared with control mice. The immunization resulted in reduced bacterial load in the respiratory tissues, following lung infection with S. pneumoniae TIGR4 or D39, compared with control mice. With the S. mitis TIGR4cps, protection upon challenge with S. pneumoniae TIGR4 was superior. Thus, these findings show the S. mitis potential to elicit natural serotype-independent protection against two pneumococcal serotypes and to provide the benefits of the well-recognized protective effect of capsule-targeting vaccines. IMPORTANCE Streptococcus pneumoniae causes various diseases worldwide. Current pneumococcal vaccines protect against limited number of more than 90 pneumococcal serotypes, accentuating the urgent need to develop novel prophylactic strategies. S. pneumoniae and the commensal Streptococcus mitis share immunogenic characteristics, which make the S. mitis an attractive vaccine candidate against S. pneumoniae . In this study, we evaluated the potential of S. mitis and its mutant expressing the pneumococcal capsule type 4 ( S. mitis TIGR4cps) to induce protection against S. pneumoniae lung infection in mice. Our findings show that intranasal vaccination with S. mitis protects against S. 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 against S. pneumoniae TIGR4, but not against D39. The findings highlight the potential of S. mitis to generate protection that combines both serotype-independent and serotype-specific responses.