Development of a Recombinant Fusion Vaccine Candidate Against Lethal Neurotoxin Types A and B.

BACKGROUND

Botulinum neurotoxins (BoNTs), produced by , are potent protein toxins that can cause botulism, which leads to death or neuroparalysis in humans by targeting the nervous system. BoNTs comprise three functional domains: a light-chain enzymatic domain (LC), a heavy-chain translocation domain (HC), and a heavy-chain receptor-binding domain (HC). The HC domain is critical for binding to neuronal cell membrane receptors and facilitating BoNT internalization via endocytosis. Accordingly, it may serve as a vaccine candidate, inducing anti-BoNT-neutralizing antibodies in animals. Here, we aimed to develop a vaccine capable of simultaneously defending against both BoNT/A and B.

METHODS

We combined the HC domains of botulinum neurotoxin type A (BoNT/A) and botulinum neurotoxin type B (BoNT/B) in to produce a recombinant protein (rHCB-L-HCArHCcB) that offers dual protection against both toxins by inhibiting their receptor binding. To evaluate the efficacy of the vaccine, mice were immunized intramuscularly with rHCB-L-HCA plus alum thrice at 2-week intervals, followed by the assessment of immunogenicity and protective efficacy.

RESULTS

The antibody titer in mice immunized with rHCB-L-HCA was significantly higher than that in mice immunized with alum alone, protecting them from the lethal challenges of BoNT/A (10 50% lethal dose, LD) and B (10 LD).

CONCLUSION

These findings suggest that rHCB-L-HCA may simultaneously be an effective vaccine candidate against BoNT/A and B.