Development of a Recombinant Fusion Vaccine Candidate Against Lethal <i>Clostridium botulinum</i> Neurotoxin Types A and B
Background: Botulinum neurotoxins (BoNTs), produced by <i>Clostridium botulinum</i>, 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 domai...
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| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-01-01
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| Series: | Vaccines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-393X/13/1/39 |
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| Summary: | Background: Botulinum neurotoxins (BoNTs), produced by <i>Clostridium botulinum</i>, 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<sub>N</sub>), and a heavy-chain receptor-binding domain (HC<sub>C</sub>). The HC<sub>C</sub> 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<sub>C</sub> domains of botulinum neurotoxin type A (BoNT/A) and botulinum neurotoxin type B (BoNT/B) in <i>Escherichia coli</i> to produce a recombinant protein (rHC<sub>C</sub>B-L-HC<sub>C</sub>ArHCcB) that offers dual protection against both toxins by inhibiting their receptor binding. To evaluate the efficacy of the vaccine, mice were immunized intramuscularly with rHC<sub>C</sub>B-L-HC<sub>C</sub>A plus alum thrice at 2-week intervals, followed by the assessment of immunogenicity and protective efficacy. Results: The antibody titer in mice immunized with rHC<sub>C</sub>B-L-HC<sub>C</sub>A was significantly higher than that in mice immunized with alum alone, protecting them from the lethal challenges of BoNT/A (10<sup>5</sup> 50% lethal dose, LD<sub>50</sub>) and B (10<sup>3</sup> LD<sub>50</sub>). Conclusion: These findings suggest that rHC<sub>C</sub>B-L-HC<sub>C</sub>A may simultaneously be an effective vaccine candidate against BoNT/A and B. |
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| ISSN: | 2076-393X |