An Effective Prophylactic and Therapeutic Protection Against Botulinum Type A Intoxication in Mice and Rabbits Using a Humanized Monoclonal Antibody.

IF 3.9 3区医学 Q2 FOOD SCIENCE & TECHNOLOGY

Toxins Pub Date : 2025-03-14 DOI:10.3390/toxins17030138

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

{"title":"An Effective Prophylactic and Therapeutic Protection Against Botulinum Type A Intoxication in Mice and Rabbits Using a Humanized Monoclonal Antibody.","authors":"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","doi":"10.3390/toxins17030138","DOIUrl":null,"url":null,"abstract":"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 LD50 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 LD50. The results indicated that 5 mg of HZ45 could treat the NZWs within 8 h after exposure to 10 LD50 botulinum. Consequently, in an in vivo context, including mice and rabbits, HZ45 mAb could protect against botulinum type A intoxication.","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 3","pages":""},"PeriodicalIF":3.9000,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11946523/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Toxins","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3390/toxins17030138","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"FOOD SCIENCE & TECHNOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

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 LD₅₀ 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 LD₅₀. The results indicated that 5 mg of HZ45 could treat the NZWs within 8 h after exposure to 10 LD₅₀ botulinum. Consequently, in an in vivo context, including mice and rabbits, HZ45 mAb could protect against botulinum type A intoxication.

查看原文本刊更多论文

求助全文

约1分钟内获得全文求助全文

来源期刊

Toxins TOXICOLOGY-

CiteScore

7.50

自引率

16.70%

发文量

765

审稿时长

16.24 days

期刊介绍： Toxins (ISSN 2072-6651) is an international, peer-reviewed open access journal which provides an advanced forum for studies related to toxins and toxinology. It publishes reviews, regular research papers and short communications. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced.