TH17-Based Vaccine Design for Prevention of Streptococcus pneumoniae Colonization

Abstract

Summary Streptococcus 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 harnessing TH17-mediated immunity.

Directed vaccination against pneumococcal disease

“…The latter result indicates an important role of the humoral immune system arm in the mechanism driving the results obtained throughout this study and suggests that an additional T-cell response also contributes. Interestingly, these observations are in line with the recognition that priming of T H 17 cells is an important factor mediating the clearance of pathogens at mucosal surfaces (42). However, a more mechanistic analysis of individual and combined antigens is required to characterize better the immunological underpinnings of the results presented.…”

Serotype-independent pneumococcal experimental vaccines that induce cellular as well as humoral immunity

“…In recent efforts using tools from proteomics and chromatography, the WCA soluble fraction was used as a source for the identification of pneumococcal antigens that, when administered alone, could confer protection against pneumococcal colonization in mice. Several such proteins have been identified (47). These findings are presently the limit of structure-function information on the WCA.…”

“…A protein that is not essential for viability but significant in immunological recognition by the host can be altered or eliminated (e.g., a major recent study addressing the issue described two strains in which surface proteins with vaccine potential were not expressed) (27). Candidate vaccines combining several common proteins (42,47), in addition to gaining potency, may reduce the possibility that pneumococcus would readily evolve to evade immunity induced by vaccination.…”

Cytokine responses in primary and secondary respiratory syncytial virus infections

“…Hence, the generation of pathogen-specific IL-17 cells may be an important component of effective secondary responses to respiratory pathogens (15). IL-17-producing T cells are induced in primary infections through pathways that involve STAT3 and IL-6 (16,17).…”