Development of an Equine Antitoxin by Immunizing the Halla Horse with the Receptor-Binding Domain of Botulinum Neurotoxin Type A1.
Abstract: Botulinum neurotoxins (BoNTs), produced by , are the most toxic substances known. However, the number of currently approved medical countermeasures for these toxins is very limited. Therefore, studies on therapeutic antitoxins are essential to prepare for toxin-related emergencies. Currently, more than 10,000 Halla horses, a crossbreed between the native Jeju and Thoroughbred horses, are being raised in Jeju Island of Korea. They can be used for equine antitoxin experiments and production of hyperimmune serum against BoNT/A1. Instead of the inactivated BoNT/A1 toxoid, Halla horse was immunized with the receptor-binding domain present in the C-terminus of heavy chain of BoNT/A1 (BoNT/A1-HCR) expressed in . The anti-BoNT/A1-HCR antibody titer increased rapidly by week 4, and this level was maintained for several weeks after boosting immunization. Notably, 20 μL of the week 24 BoNT/A1-HCR(-immunized) equine serum showed an in vitro neutralizing activity of over 8 international unit (IU) of a reference equine antitoxin. Furthermore, 20 μL of equine serum and 100 μg of purified equine F(ab') showed 100% neutralization of 10,000 LD in vivo. The results of this study shall contribute towards optimizing antitoxin production for BoNT/A1, which is essential for emergency preparedness and response.
Publication Date: 2019-07-10 PubMed ID: 31280529DOI: 10.4014/jmb.1904.04027Google Scholar: Lookup
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- Journal Article
Summary
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This research reports on developing an antitoxin to counter the effects of a highly potent toxin, Botulinum Neurotoxins Type A1, using the Halla horse as a source of antitoxin serum.
Background
- Botulinum neurotoxins (BoNTs) are produced by bacteria and are considered the most poisonous substances. Despite their high toxicity, there are few medical countermeasures currently approved for these toxins. The research on therapeutic antitoxins is critical to prepare for emergency situations related to toxin exposure.
Study Design and Methodology
- The study utilized more than 10,000 Halla horses, a crossbreed between Jeju and Thoroughbred horses raised in Jeju Island, Korea, for the experiments. The researchers used these horses to test the production of a serum against BoNT/A1 toxin.
- For immunization, the researchers adopted a different approach. Rather than using the entire inactivated BoNT/A1 toxoid, they utilized the receptor-binding domain present at the end region of the heavy chain in the toxin. This segment was expressed in the horses using biotechnological methods.
Results & Findings
- The immunization was effective, with increased levels of anti-BoNT/A1-HCR antibody found by week 4. This response was maintained for several weeks after the secondary immunization (boosting).
- At week 24, the antitoxin produced by the horse’s immune system successfully neutralized the effects of the toxin in vitro at over 8 international unit (IU) of a reference equine antitoxin.
- Moreover, the serum and a specific fragment of the equine antibody achieved 100% neutralization of a massive dose of the toxin during in vivo trials.
Conclusions
- The results from this study contribute to improving the production of antitoxins for BoNT/A1. Such developments are crucial for being prepared for and responding to emergencies caused by exposure to this highly toxic substance.
Cite This Article
APA
Kim NY, Park KE, Lee YJ, Kim YM, Hong SH, Son WR, Hong S, Lee S, Ahn HB, Yang J, Seo JP, Lim YK, Yu CH, Hur GH, Jeong ST, Lee HS, Song K, Kang TJ, Shin YK, Choi JS, Choi JY.
(2019).
Development of an Equine Antitoxin by Immunizing the Halla Horse with the Receptor-Binding Domain of Botulinum Neurotoxin Type A1.
J Microbiol Biotechnol, 29(7), 1165-1176.
https://doi.org/10.4014/jmb.1904.04027 Publication
Researcher Affiliations
- ABION Inc., R&D Center, Seoul 08394, Republic of Korea.
- ABION Inc., R&D Center, Seoul 08394, Republic of Korea.
- ABION Inc., R&D Center, Seoul 08394, Republic of Korea.
- ABION Inc., R&D Center, Seoul 08394, Republic of Korea.
- ABION Inc., R&D Center, Seoul 08394, Republic of Korea.
- ABION Inc., R&D Center, Seoul 08394, Republic of Korea.
- Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea.
- Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea.
- Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 08826, Republic of Korea.
- Korea National College of Agriculture and Fisheries, Jeonju 54874, Republic of Korea.
- College of Veterinary Medicine, Jeju National University, Jeju 63309, Republic of Korea.
- College of Veterinary Medicine, Jeju National University, Jeju 63309, Republic of Korea.
- Agency for Defense Development, Daejeon 34186, Republic of Korea.
- Agency for Defense Development, Daejeon 34186, Republic of Korea.
- Agency for Defense Development, Daejeon 34186, Republic of Korea.
- LOGONE Bio Convergence Research Foundation, CRO Center, Seoul 08826, Republic Korea.
- LOGONE Bio Convergence Research Foundation, The Center for Companion Diagnostics, Seoul 08826, Republic Korea.
- College of Pharmacy, Sahmyook University, Seoul 01795, Republic of Korea.
- Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea.
- Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 08826, Republic of Korea.
- College of Pharmacy, Daegu Catholic University, Daegu 38430, Republic of Korea.
- ABION Inc., R&D Center, Seoul 08394, Republic of Korea.
- Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea.
MeSH Terms
- Animals
- Antibodies, Bacterial / blood
- Antibodies, Bacterial / immunology
- Bacterial Vaccines / chemistry
- Bacterial Vaccines / immunology
- Botulinum Antitoxin / blood
- Botulinum Antitoxin / immunology
- Botulinum Toxins, Type A / chemistry
- Botulinum Toxins, Type A / immunology
- Clostridium botulinum / immunology
- Female
- Horses
- Immunization / veterinary
- Mice, Inbred BALB C
- Neutralization Tests / veterinary
- Peptide Fragments / chemistry
- Peptide Fragments / immunology
- Rabbits
Citations
This article has been cited 1 times.- Shi DY, Lu JS, Mao YY, Liu FJ, Wang R, Du P, Yu S, Yu YZ, Yang ZX. Characterization of a novel tetravalent botulism antitoxin based on receptor-binding domain of BoNTs. Appl Microbiol Biotechnol 2023 May;107(10):3205-3216.
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