Development of an Equine Antitoxin by Immunizing the Halla Horse with the Receptor-Binding Domain of Botulinum Neurotoxin Type A1

Kim, Na Young; Park, Kyung-eui; Lee, Yong Jin; Kim, Yeong Mun; Hong, Sung Hwan; Son, Weon-Young; Hong, Sung Kyu; Lee, Saehyung; Ahn, Hye Bin; Yang, Jae-Hyuk; Seo, Jong-pil; Lim, Yoon-Kyu; Yu, Chi Ho; Hur, Gyeung Haeng; Jeong, Seong Tae; Lee, Hun Seok; Song, Kyoung; Kang, Tae Jin; Shin, Young Kee; Choi, Joon-Seok; Choi, Jun Young

doi:10.4014/jmb.1904.04027

Cited by 1 publication

(2 citation statements)

References 56 publications

(70 reference statements)

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“…According to previously published methods, we prepared total equine IgG and F(ab′) 2 (Kim et al 2019;Shi et al 2020;Wang et al 2005). Briefly, pyrogen-free distilled water was used to dilute the hyperimmune sera (1:2 v/v) and the pH was adjusted to 3.0 using 1 N HCl.…”

Section: Preparation and Properties Of Monovalent Batsmentioning

confidence: 99%

“…Genetically engineered monoclonal antibodies are also in the development stage (Raja et al 2022;Rasetti-Escargueil et al 2017;Tomic et al 2021). However, technologically, equine-derived BAT is the most mature BAT available to date (Kim et al 2019;Rasseti-Escargueil and Popoff 2019;Richardson et al 2020). The H-BAT and other traditionary antitoxins were derived from the plasma of horses immunized with inactivated toxins or toxoid, which is harmful to the animals and limits the potency of the antitoxins.…”

Section: Introductionmentioning

confidence: 99%

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Characterization of a novel tetravalent botulism antitoxin based on receptor-binding domain of BoNTs

Shi¹,

Lu²,

Mao³

et al. 2023

Appl Microbiol Biotechnol

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Botulinum neurotoxin (BoNTs; serotypes A, B, E, and F) cause botulism disease in humans, which could be effectively treated using antitoxins. Herein, we established a novel receptor-binding domain (RBD)-based antitoxin using recombinant C terminal heavy chain (Hc) domains of BoNTs as immunogens. Immunization of horses with these recombinant Hc domains allowed the purification and digestion of IgGs from hyper-immune sera to produce high-quality and high-efficiency monovalent botulism antitoxin F(ab′) 2 against each BoNT (M-BATs). However, these M-BATs could not bind or neutralize other serotypes of BoNTs, and that there were no cross-protective effects among these M-BATs. This suggested the need to prepare tetravalent antitoxins to neutralize the four BoNTs simultaneously. Thus, these M-BATs were formulated into a novel tetravalent botulism antitoxin (T-BAT), in which a 10-ml volume contained 10000 IU of BoNT/A and 5000 IU of BoNT/B, BoNT/E, and BoNT/F antitoxins. The novel antitoxin preparation could prevent and treat the four mixed botulinum neurotoxins simultaneously in vivo, representing strong efficacy in an animal poisoning model. Moreover, these antibodies in T-BAT could bind the RBD, whereas conventional antitoxins based on inactivated toxins mainly bind the light chain or heavy chain translocation domain (HN) and weakly bind the important RBD in current experimental conditions. The high levels of RBD-specific novel antitoxins can efficiently bind the RBD and neutralize natural or recombinant toxins containing this RBD. The findings of the present study experimentally support the use of RBD-specific antitoxins to treat BoNT serotype A, B, E, and F-mediated botulism. This study demonstrated the concept of developing potent novel multivalent antitoxins against all BoNTs or other toxins, using the RBD of these toxins as an alternative antigen to inactivated toxins. Key points • Antitoxins based on the receptor-binding domains of botulinum neurotoxins were made. • Novel antitoxin binds RBD; traditional antitoxin mainly binds light chain or HN domain. • A tetravalent antitoxin could prevent and treat the four mixed neurotoxins in vivo. Supplementary Information The online version contains supplementary material available at 10.1007/s00253-023-12515-2.

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Section: Preparation and Properties Of Monovalent Batsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Characterization of a novel tetravalent botulism antitoxin based on receptor-binding domain of BoNTs

Shi¹,

Lu²,

Mao³

et al. 2023

Appl Microbiol Biotechnol

View full text Add to dashboard Cite

show abstract

Development of an Equine Antitoxin by Immunizing the Halla Horse with the Receptor-Binding Domain of Botulinum Neurotoxin Type A1

Abstract: showed 100% neutralization of 10,000 LD 5 0 in vivo. The results of this study shall contribute towards optimizing antitoxin production for BoNT/A1, which is essential for emergency preparedness and response.

Cited by 1 publication

References 56 publications

Characterization of a novel tetravalent botulism antitoxin based on receptor-binding domain of BoNTs

Characterization of a novel tetravalent botulism antitoxin based on receptor-binding domain of BoNTs

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