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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2025-01-01
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| author | Eun-Sun Choi Seong-Wook Pyo So-Hyeon Kim Jun-Ho Jeon Gi-Eun Rhie Mi-Ran Yun Hwajung Yi Yoon-Seok Chung |
| author_facet | Eun-Sun Choi Seong-Wook Pyo So-Hyeon Kim Jun-Ho Jeon Gi-Eun Rhie Mi-Ran Yun Hwajung Yi Yoon-Seok Chung |
| author_sort | Eun-Sun Choi |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-870d7b4de1444da3831fa7987ad045c5 |
| institution | Kabale University |
| issn | 2076-393X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
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| series | Vaccines |
| spelling | doaj-art-870d7b4de1444da3831fa7987ad045c52025-01-24T13:51:44ZengMDPI AGVaccines2076-393X2025-01-011313910.3390/vaccines13010039Development of a Recombinant Fusion Vaccine Candidate Against Lethal <i>Clostridium botulinum</i> Neurotoxin Types A and BEun-Sun Choi0Seong-Wook Pyo1So-Hyeon Kim2Jun-Ho Jeon3Gi-Eun Rhie4Mi-Ran Yun5Hwajung Yi6Yoon-Seok Chung7Division of High-Risk Pathogens, Department of Laboratory Diagnosis and Analysis, Korea Disease Control and Prevention Agency, KDCA, Cheongju 28159, Republic of KoreaDivision of High-Risk Pathogens, Department of Laboratory Diagnosis and Analysis, Korea Disease Control and Prevention Agency, KDCA, Cheongju 28159, Republic of KoreaDivision of High-Risk Pathogens, Department of Laboratory Diagnosis and Analysis, Korea Disease Control and Prevention Agency, KDCA, Cheongju 28159, Republic of KoreaDivision of Infectious Disease Diagnosis, Chungcheong Regional Center for Disease Control and Prevention, Korea Disease Control and Prevention Agency, KDCA, Cheongju 28159, Republic of KoreaDirector General, Center for Vaccine Research, National Institute of Health, Korea Disease Control and Prevention Agency, KDCA, Cheongju 28159, Republic of KoreaDivision of Infectious Disease Vaccine Research, Center for Vaccine Research, National Institute of Health, Korea Disease Control and Prevention Agency, KDCA, Cheongju 28159, Republic of KoreaDivision of High-Risk Pathogens, Department of Laboratory Diagnosis and Analysis, Korea Disease Control and Prevention Agency, KDCA, Cheongju 28159, Republic of KoreaDivision of High-Risk Pathogens, Department of Laboratory Diagnosis and Analysis, Korea Disease Control and Prevention Agency, KDCA, Cheongju 28159, Republic of KoreaBackground: 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.https://www.mdpi.com/2076-393X/13/1/39<i>Clostridium botulinum</i>botulismneurotoxinfusion vaccinereceptor binding domain |
| spellingShingle | Eun-Sun Choi Seong-Wook Pyo So-Hyeon Kim Jun-Ho Jeon Gi-Eun Rhie Mi-Ran Yun Hwajung Yi Yoon-Seok Chung Development of a Recombinant Fusion Vaccine Candidate Against Lethal <i>Clostridium botulinum</i> Neurotoxin Types A and B Vaccines <i>Clostridium botulinum</i> botulism neurotoxin fusion vaccine receptor binding domain |
| title | Development of a Recombinant Fusion Vaccine Candidate Against Lethal <i>Clostridium botulinum</i> Neurotoxin Types A and B |
| title_full | Development of a Recombinant Fusion Vaccine Candidate Against Lethal <i>Clostridium botulinum</i> Neurotoxin Types A and B |
| title_fullStr | Development of a Recombinant Fusion Vaccine Candidate Against Lethal <i>Clostridium botulinum</i> Neurotoxin Types A and B |
| title_full_unstemmed | Development of a Recombinant Fusion Vaccine Candidate Against Lethal <i>Clostridium botulinum</i> Neurotoxin Types A and B |
| title_short | Development of a Recombinant Fusion Vaccine Candidate Against Lethal <i>Clostridium botulinum</i> Neurotoxin Types A and B |
| title_sort | development of a recombinant fusion vaccine candidate against lethal i clostridium botulinum i neurotoxin types a and b |
| topic | <i>Clostridium botulinum</i> botulism neurotoxin fusion vaccine receptor binding domain |
| url | https://www.mdpi.com/2076-393X/13/1/39 |
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