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

Abstract Background Streptococcus suis (S. suis) is a zoonotic pathogen causing economic losses in the swine industry and severe human infections. High serotype variability and genomic diversity of S. suis hinder cross-protective vaccine development. Although advances in in silico prediction-driven antigen discovery have accelerated protein vaccine development, discrepancies between predicted immunogenicity and experimentally verified protection in animal models emphasize the need to integrate computational design with empirical validation. Methods Using an in silico design strategy, predicted T- and B-cell epitope-rich domains from S. suis antigens (HP0197, Fnbp, Sao, ScpB, and SLY) were assembled into a multimeric vaccine, ATOMSSUISpenta, optimized for predicted immunogenicity, solubility, and allergenicity. Vaccine efficacy was evaluated in mice through antibody profiling, cellular immunity analysis, and assessment of cross-serotype immunity. Results ATOMSSUISpenta elicited strong humoral responses against all component antigens. The vaccine also induced Th1- and Th17-type cellular responses, critical for opsonic and mucosal defense against S. suis. In addition, ATOMSSUISpenta conferred significant protection in a S. suis serotype 2 infection and induced opsonic antibodies against serotypes 4 and 9. Conclusions These findings highlight ATOMSSUISpenta as a subunit vaccine strategy with potential for broader protection and demonstrate the effectiveness of epitope-based multimeric design against antigenically diverse Gram-positive pathogens.