An Effective Prophylactic and Therapeutic Protection Against Botulinum Type A Intoxication in Mice and Rabbits Using a Humanized Monoclonal Antibody
Botulinum neurotoxins (BoNTs) are the most potent toxins on Earth and are classified as Category A biological agents. BoNTs lead to paralysis in humans and cause botulism. Antibody therapeutics can effectively treat toxin-mediated infectious diseases. In this study, we generated a pharmaceutical hum...
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MDPI AG
2025-03-01
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| Series: | Toxins |
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| Online Access: | https://www.mdpi.com/2072-6651/17/3/138 |
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| author | Chi Ho Yu Young-Jo Song Dong Hyun Song Hae Eun Joe Chang-Hwan Kim Hyungseok Yun Na Young Kim Euni Sim Seong Tae Jeong Gyeung Haeng Hur |
| author_facet | Chi Ho Yu Young-Jo Song Dong Hyun Song Hae Eun Joe Chang-Hwan Kim Hyungseok Yun Na Young Kim Euni Sim Seong Tae Jeong Gyeung Haeng Hur |
| author_sort | Chi Ho Yu |
| collection | DOAJ |
| description | Botulinum neurotoxins (BoNTs) are the most potent toxins on Earth and are classified as Category A biological agents. BoNTs lead to paralysis in humans and cause botulism. Antibody therapeutics can effectively treat toxin-mediated infectious diseases. In this study, we generated a pharmaceutical humanized monoclonal antibody (HZ45 mAb) to prevent or treat botulism. HZ45 binds to the heavy chain receptor (HCR) domain of the toxin, preventing the toxin from entering the cell. The mAb was produced using hybridoma technology and phage display. We evaluated HZ45 mAb for the neutralization of BoNT serotype A (BoNT/A) in mice and rabbits. The survival results showed that pretreatment with HZ45 mAb provided 100% protection at a dose of 0.1 mg per mouse against a maximum of 100 LD<sub>50</sub> of BoNT/A. To assess the therapeutic efficacy of HZ45 mAb in New Zealand white rabbits (NZWs), a 5 mg dose was administered 4 or 8 h after challenge with 10 LD<sub>50</sub>. The results indicated that 5 mg of HZ45 could treat the NZWs within 8 h after exposure to 10 LD<sub>50</sub> botulinum. Consequently, in an in vivo context, including mice and rabbits, HZ45 mAb could protect against botulinum type A intoxication. |
| format | Article |
| id | doaj-art-8ae02c730e404817bc8f5fefbb6acdd2 |
| institution | DOAJ |
| issn | 2072-6651 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj-art-8ae02c730e404817bc8f5fefbb6acdd22025-08-20T02:43:04ZengMDPI AGToxins2072-66512025-03-0117313810.3390/toxins17030138An Effective Prophylactic and Therapeutic Protection Against Botulinum Type A Intoxication in Mice and Rabbits Using a Humanized Monoclonal AntibodyChi Ho Yu0Young-Jo Song1Dong Hyun Song2Hae Eun Joe3Chang-Hwan Kim4Hyungseok Yun5Na Young Kim6Euni Sim7Seong Tae Jeong8Gyeung Haeng Hur9Agency for Defense Development, Yuseong, P.O. Box 35, Daejeon 305-600, Republic of KoreaAgency for Defense Development, Yuseong, P.O. Box 35, Daejeon 305-600, Republic of KoreaAgency for Defense Development, Yuseong, P.O. Box 35, Daejeon 305-600, Republic of KoreaAgency for Defense Development, Yuseong, P.O. Box 35, Daejeon 305-600, Republic of KoreaAgency for Defense Development, Yuseong, P.O. Box 35, Daejeon 305-600, Republic of KoreaAgency for Defense Development, Yuseong, P.O. Box 35, Daejeon 305-600, Republic of KoreaABION Inc., Seoul 08394, Republic of KoreaABION Inc., Seoul 08394, Republic of KoreaAgency for Defense Development, Yuseong, P.O. Box 35, Daejeon 305-600, Republic of KoreaAgency for Defense Development, Yuseong, P.O. Box 35, Daejeon 305-600, Republic of KoreaBotulinum neurotoxins (BoNTs) are the most potent toxins on Earth and are classified as Category A biological agents. BoNTs lead to paralysis in humans and cause botulism. Antibody therapeutics can effectively treat toxin-mediated infectious diseases. In this study, we generated a pharmaceutical humanized monoclonal antibody (HZ45 mAb) to prevent or treat botulism. HZ45 binds to the heavy chain receptor (HCR) domain of the toxin, preventing the toxin from entering the cell. The mAb was produced using hybridoma technology and phage display. We evaluated HZ45 mAb for the neutralization of BoNT serotype A (BoNT/A) in mice and rabbits. The survival results showed that pretreatment with HZ45 mAb provided 100% protection at a dose of 0.1 mg per mouse against a maximum of 100 LD<sub>50</sub> of BoNT/A. To assess the therapeutic efficacy of HZ45 mAb in New Zealand white rabbits (NZWs), a 5 mg dose was administered 4 or 8 h after challenge with 10 LD<sub>50</sub>. The results indicated that 5 mg of HZ45 could treat the NZWs within 8 h after exposure to 10 LD<sub>50</sub> botulinum. Consequently, in an in vivo context, including mice and rabbits, HZ45 mAb could protect against botulinum type A intoxication.https://www.mdpi.com/2072-6651/17/3/138botulinum neurotoxinmonoclonal antibodymouserabbit |
| spellingShingle | Chi Ho Yu Young-Jo Song Dong Hyun Song Hae Eun Joe Chang-Hwan Kim Hyungseok Yun Na Young Kim Euni Sim Seong Tae Jeong Gyeung Haeng Hur An Effective Prophylactic and Therapeutic Protection Against Botulinum Type A Intoxication in Mice and Rabbits Using a Humanized Monoclonal Antibody Toxins botulinum neurotoxin monoclonal antibody mouse rabbit |
| title | An Effective Prophylactic and Therapeutic Protection Against Botulinum Type A Intoxication in Mice and Rabbits Using a Humanized Monoclonal Antibody |
| title_full | An Effective Prophylactic and Therapeutic Protection Against Botulinum Type A Intoxication in Mice and Rabbits Using a Humanized Monoclonal Antibody |
| title_fullStr | An Effective Prophylactic and Therapeutic Protection Against Botulinum Type A Intoxication in Mice and Rabbits Using a Humanized Monoclonal Antibody |
| title_full_unstemmed | An Effective Prophylactic and Therapeutic Protection Against Botulinum Type A Intoxication in Mice and Rabbits Using a Humanized Monoclonal Antibody |
| title_short | An Effective Prophylactic and Therapeutic Protection Against Botulinum Type A Intoxication in Mice and Rabbits Using a Humanized Monoclonal Antibody |
| title_sort | effective prophylactic and therapeutic protection against botulinum type a intoxication in mice and rabbits using a humanized monoclonal antibody |
| topic | botulinum neurotoxin monoclonal antibody mouse rabbit |
| url | https://www.mdpi.com/2072-6651/17/3/138 |
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