TH17-Based Vaccine Design for Prevention of Streptococcus pneumoniae Colonization

SummaryStreptococcus pneumoniae is a leading cause of mortality in young children. While successful conjugate polysaccharide vaccines exist, a less expensive serotype-independent protein-based pneumococcal vaccine offers a major advancement for preventing life-threatening pneumococcal infections, particularly in developing nations. IL-17A-secreting CD4+ T cells (TH17) mediate resistance to mucosal colonization by multiple pathogens including S. pneumoniae. Screening an expression library containing >96% of predicted pneumococcal proteins, we identified antigens recognized by TH17 cells from mice immune to pneumococcal colonization. The identified antigens also elicited IL-17A secretion from colonized mouse splenocytes and human PBMCs suggesting that similar responses are primed during natural exposure. Immunization of two mouse strains with identified antigens provided protection from pneumococcal colonization that was significantly diminished in animals treated with blocking CD4 or IL-17A antibodies. This work demonstrates the potential of proteomic screening approaches to identify specific antigens for the design of subunit vaccines against mucosal pathogens via harnessingTH17-mediated immunity.

► Comprehensive proteomic screening identifies pneumococcal TH17 cell antigens
► TH17 cells from colonized mice and humans recognize selected antigens
► Purified protein antigens protect naive mice against pneumococcal colonization
► Vaccine-elicited protection from colonization depends on CD4+ T cells and IL-17A