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

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 , a commensal that exhibits immune cross-reactivity with , to confer protective immunity to lung infection in mice. First, we assessed the immune response and protective effect of wild-type against lung infection by strains D39 (serotype 2) and TIGR4 (serotype 4). Second, we examined the ability of an mutant expressing the type 4 capsule ( TIGR4cps) to elicit focused protection against TIGR4. Our results showed that intranasal immunization of mice with produced significantly higher levels of serum IgG and IgA antibodies reactive to both and , as well as enhanced production of interleukin 17A (IL-17A), but not gamma interferon (IFN-γ) and IL-4, compared with control mice. The immunization resulted in a reduced bacterial load in respiratory tissues following lung infection with TIGR4 or D39 compared with control mice. With TIGR4cps, protection upon challenge with TIGR4 was superior. Thus, these findings show the potential of 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. 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. and the commensal share immunogenic characteristics that make an attractive vaccine candidate against In this study, we evaluated the potential of and its mutant expressing pneumococcal capsule type 4 ( TIGR4cps) to induce protection against lung infection in mice. Our findings show that intranasal vaccination with protects against strains D39 (serotype 2) and TIGR4 (serotype 4) in a serotype-independent fashion, which is associated with enhanced antibody and T cell responses. Furthermore, TIGR4cps conferred additional protection against TIGR4, but not against D39. The findings highlight the potential of to generate protection that combines both serotype-independent and serotype-specific responses.