Synthetic peptide vaccines targeting SVA elicit robust protective immune responses in swine

Senecavirus A (SVA), an emerging pathogen in swine, causes vesicular disease with clinical manifestations similar to foot-and-mouth disease (FMD), vesicular stomatitis (VS), and swine vesicular disease (SVD), posing a significant economic threat to the global swine industry. Therefore, it is of vital importance to develop a safe and effective SVA vaccine. In this study, guided by the principles of synthetic biology, we designed and synthesized two SVA candidate synthetic peptides, TT-073 and TT-074, based on the highly conserved B-cell neutralizing epitope VP2_150-160aa from the SVA capsid protein, and a helper T-cell epitope derived from the F protein of the urticaria virus. These peptides were synthesized using solid-phase peptide synthesis (SPPS). Initially, we systematically evaluated the immunogenicity of the synthetic peptides in mice when combined with various adjuvants. The results demonstrated that the Montanide ISA 50Vc adjuvant, in conjunction with the synthetic peptides, elicited the most robust immune response. Building upon this finding, we subsequently formulated the TT-073 and TT-074 synthetic peptide vaccines in varying dosage regimens with Montanide ISA 50Vc adjuvant for swine immunization. Compared to TT-073 synthetic peptide, the TT-074 synthetic peptide exhibited superior immunogenicity. Notably, the high-dose formulation of the TT-074 synthetic peptide induced higher levels of neutralizing antibodies (1:111) while effectively activating both humoral and cellular immune responses, thereby providing robust protection against SVA challenge. This study underscores the immense potential of synthetic biology in vaccine development and provides critical theoretical insights for the future development of synthetic peptide vaccines targeting other pathogens.