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Volume 13
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Article

A Monoclonal Antibody Combination against both Serotypes A and B Botulinum Toxin Prevents Inhalational Botulism in a Guinea Pig Model

by
Doris M. Snow
1,
Ronald R. Cobb
1,
Juan Martinez
1,
Isaac Finger-Baker
1,
Laura Collins
1,
Sara Terpening
1,
Emily S. Syar
2,
Nancy Niemuth
2,
Dean Kobs
2,
Roy Barnewall
2,
Shauna Farr-Jones
3,
James D. Marks
3 and
Milan T. Tomic
4,*
1
Ology Bioservices, 13200 NW, Nano Ct, Alachua, FL 32615, USA
2
Battelle Biomedical Research Center, West Jefferson, Columbus, OH 43162, USA
3
Department of Anesthesia and Perioperative Care, University of California, 1001 Potrero Ave., San Francisco, CA 94110, USA
4
Research and Development, Ology Bioservices, Inc., 2061 Challenger Dr., Alameda, CA 94501, USA
*
Author to whom correspondence should be addressed.
Toxins 2021, 13(1), 31; https://doi.org/10.3390/toxins13010031
Submission received: 13 November 2020 / Revised: 23 December 2020 / Accepted: 29 December 2020 / Published: 5 January 2021
(This article belongs to the Section Bacterial Toxins)
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Abstract

Botulinum neurotoxins (BoNT) are extremely potent and can induce respiratory failure, requiring long-term intensive care to prevent death. Recombinant monoclonal antibodies (mAbs) hold considerable promise as BoNT therapeutics and prophylactics. In contrast, equine antitoxin cannot be used prophylactically and has a short half-life. Two three-mAb combinations are in development that specifically neutralize BoNT serotype A (BoNT/A) and B (BoNT/B). The three-mAb combinations addressing a single serotype provided pre-exposure prophylaxis in the guinea pig inhalation model. A lyophilized co-formulation of six mAbs, designated G03-52-01, that addresses both A and B serotypes is in development. Here, we investigated the efficacy of G03-52-01 to protect guinea pigs against an aerosol exposure challenge of BoNT/A1 or BoNT/B1. Previously, it was found that each antibody demonstrated a dose-dependent exposure and reached maximum circulating concentrations within 48 h after intramuscular (IM) or intravenous (IV) injection. Here we show that G03-52-01, in a single IM injection of G03-52-01 administered 48 h pre-exposure, protected guinea pigs against an aerosol challenge of up to 238 LD50s of BoNT/A1 and 191 LD50s of BoNT/B1. These data suggest that a single IM administration of G03-52-01 provides pre-exposure prophylaxis against botulism from an aerosol exposure of BoNT/A1 or BoNT/B1.
Keywords: botulinum neurotoxin; aerosol; monoclonal antibody; guinea pig inhalation model; oligoclonal antibody; botulism botulinum neurotoxin; aerosol; monoclonal antibody; guinea pig inhalation model; oligoclonal antibody; botulism

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MDPI and ACS Style

Snow, D.M.; Cobb, R.R.; Martinez, J.; Finger-Baker, I.; Collins, L.; Terpening, S.; Syar, E.S.; Niemuth, N.; Kobs, D.; Barnewall, R.; et al. A Monoclonal Antibody Combination against both Serotypes A and B Botulinum Toxin Prevents Inhalational Botulism in a Guinea Pig Model. Toxins 2021, 13, 31. https://doi.org/10.3390/toxins13010031

AMA Style

Snow DM, Cobb RR, Martinez J, Finger-Baker I, Collins L, Terpening S, Syar ES, Niemuth N, Kobs D, Barnewall R, et al. A Monoclonal Antibody Combination against both Serotypes A and B Botulinum Toxin Prevents Inhalational Botulism in a Guinea Pig Model. Toxins. 2021; 13(1):31. https://doi.org/10.3390/toxins13010031

Chicago/Turabian Style

Snow, Doris M., Ronald R. Cobb, Juan Martinez, Isaac Finger-Baker, Laura Collins, Sara Terpening, Emily S. Syar, Nancy Niemuth, Dean Kobs, Roy Barnewall, and et al. 2021. "A Monoclonal Antibody Combination against both Serotypes A and B Botulinum Toxin Prevents Inhalational Botulism in a Guinea Pig Model" Toxins 13, no. 1: 31. https://doi.org/10.3390/toxins13010031

APA Style

Snow, D. M., Cobb, R. R., Martinez, J., Finger-Baker, I., Collins, L., Terpening, S., Syar, E. S., Niemuth, N., Kobs, D., Barnewall, R., Farr-Jones, S., Marks, J. D., & Tomic, M. T. (2021). A Monoclonal Antibody Combination against both Serotypes A and B Botulinum Toxin Prevents Inhalational Botulism in a Guinea Pig Model. Toxins, 13(1), 31. https://doi.org/10.3390/toxins13010031

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