Epitope-Based Multimeric Subunit Vaccine (ATOMSSUISpenta) Confers Broad Protection Against Streptococcus suis Infection.

Abstract

Streptococcus suis (S. suis) is a zoonotic pathogen that causes severe economic losses in the swine industry and life-threatening infections in humans. The high serotype variability and genomic diversity of S. suis have hindered the development of cross-protective vaccines. Although recent advances in in silico prediction and database-driven antigen discovery have accelerated the development of protein-based vaccines, discrepancies between predicted immunogenicity and experimentally verified protective efficacy in animal models emphasize the need to integrate computational design with empirical validation. Using an in silico-assisted design strategy, predicted T and B cell epitope-rich domains from five S. suis antigens (HP0197, Fnbp, Sao, ScpB, and SLY) were assembled into a multimeric vaccine construct, designated ATOMSSUISpenta, through optimization for predicted immunogenicity, solubility, and allergenicity. Vaccine immunogenicity and efficacy were evaluated in mice through antigen-specific antibody profiling, cellular immunity analysis, and in vivo assessment of protective and cross-serotype immunity. ATOMSSUISpenta elicited strong antigen-specific humoral immune responses against all five component antigens in a mouse model. The vaccine also induced robust Th1- and Th17-type cellular immune responses, which are critical for effective opsonic and mucosal defense against S. suis infection. In addition, we found that ATOMSSUISpenta conferred significant protection in a S. suis serotype 2 infection model and induced opsonic antibody activities against serotypes 4 and 9. These findings highlight the potential of ATOMSSUISpenta as a subunit vaccine strategy with potential for broader protection against S. suis and demonstrate the effectiveness of epitope-based multimeric design in targeting antigenically diverse Gram-positive pathogens.