ScholarWorks@중앙대학교

초록

Botulinum neurotoxin serotype A (BoNT-A), produced by Clostridium botulinum, is one of the most potent biological toxins and is a significant bioterrorism threat. Although recombinant subunit vaccines are considered promising vaccine candidates, their detailed immunogenic profile and comprehensive safety are not yet clearly characterized. In this study, we evaluated the efficacy and safety of a mutated recombinant subunit vaccine candidate, BA15, in a murine model. Immunogenicity was assessed by measuring total IgG titers, IgG subclass distribution (IgG1 and IgG2a), and antigen-induced Th1/Th2 cytokine secretion (IFN-γ, IL-4) from splenocyte cultures. Protective efficacy was determined by survival following a lethal BoNT-A challenge. Safety was rigorously evaluated via serial monitoring of body weight, food intake, neuromuscular function (grip strength and rotarod performance), and serum biochemical markers of hepatic, renal, and metabolic function. BA15 immunization elicited robust total IgG responses, with a mild predominance of IgG1 over IgG2a, indicating a slightly Th2-skewed but balanced humoral response. Splenocytes from immunized mice produced both IFN-γ and IL-4 upon antigen stimulation, reflecting concurrent Th1 and Th2 activation. BA15 vaccination conferred complete protection against the lethal BoNT-A challenge, with 100% survival and no clinical signs of botulism. Notably, intramuscular injection of BA15 was well-tolerated; no significant differences were observed in body weight, food intake, neuromuscular test performance, or serum biochemical parameters between the BA15 group and saline-injected control group, indicating a favorable safety profile. This work supports the translational potential of BA15 as a safe and effective subunit vaccine candidate for botulism prevention and addresses key preclinical requirements for further development.

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