A Monoclonal Antibody Combination against both Serotypes A and B Botulinum Toxin Prevents Inhalational Botulism in a Guinea Pig Model
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 prophylac...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-01-01
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| Series: | Toxins |
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| Online Access: | https://www.mdpi.com/2072-6651/13/1/31 |
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| author | Doris M. Snow Ronald R. Cobb Juan Martinez Isaac Finger-Baker Laura Collins Sara Terpening Emily S. Syar Nancy Niemuth Dean Kobs Roy Barnewall Shauna Farr-Jones James D. Marks Milan T. Tomic |
| author_facet | Doris M. Snow Ronald R. Cobb Juan Martinez Isaac Finger-Baker Laura Collins Sara Terpening Emily S. Syar Nancy Niemuth Dean Kobs Roy Barnewall Shauna Farr-Jones James D. Marks Milan T. Tomic |
| author_sort | Doris M. Snow |
| collection | DOAJ |
| description | 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 LD<sub>50</sub>s of BoNT/A1 and 191 LD<sub>50</sub>s 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. |
| first_indexed | 2024-03-10T13:29:34Z |
| format | Article |
| id | doaj.art-f418db8c7f81479aaeacc484f74d01c3 |
| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-03-10T13:29:34Z |
| publishDate | 2021-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj.art-f418db8c7f81479aaeacc484f74d01c32023-11-21T08:28:45ZengMDPI AGToxins2072-66512021-01-011313110.3390/toxins13010031A Monoclonal Antibody Combination against both Serotypes A and B Botulinum Toxin Prevents Inhalational Botulism in a Guinea Pig ModelDoris M. Snow0Ronald R. Cobb1Juan Martinez2Isaac Finger-Baker3Laura Collins4Sara Terpening5Emily S. Syar6Nancy Niemuth7Dean Kobs8Roy Barnewall9Shauna Farr-Jones10James D. Marks11Milan T. Tomic12Ology Bioservices, 13200 NW, Nano Ct, Alachua, FL 32615, USAOlogy Bioservices, 13200 NW, Nano Ct, Alachua, FL 32615, USAOlogy Bioservices, 13200 NW, Nano Ct, Alachua, FL 32615, USAOlogy Bioservices, 13200 NW, Nano Ct, Alachua, FL 32615, USAOlogy Bioservices, 13200 NW, Nano Ct, Alachua, FL 32615, USAOlogy Bioservices, 13200 NW, Nano Ct, Alachua, FL 32615, USABattelle Biomedical Research Center, West Jefferson, Columbus, OH 43162, USABattelle Biomedical Research Center, West Jefferson, Columbus, OH 43162, USABattelle Biomedical Research Center, West Jefferson, Columbus, OH 43162, USABattelle Biomedical Research Center, West Jefferson, Columbus, OH 43162, USADepartment of Anesthesia and Perioperative Care, University of California, 1001 Potrero Ave., San Francisco, CA 94110, USADepartment of Anesthesia and Perioperative Care, University of California, 1001 Potrero Ave., San Francisco, CA 94110, USAResearch and Development, Ology Bioservices, Inc., 2061 Challenger Dr., Alameda, CA 94501, USABotulinum 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 LD<sub>50</sub>s of BoNT/A1 and 191 LD<sub>50</sub>s 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.https://www.mdpi.com/2072-6651/13/1/31botulinum neurotoxinaerosolmonoclonal antibodyguinea pig inhalation modeloligoclonal antibodybotulism |
| spellingShingle | Doris M. Snow Ronald R. Cobb Juan Martinez Isaac Finger-Baker Laura Collins Sara Terpening Emily S. Syar Nancy Niemuth Dean Kobs Roy Barnewall Shauna Farr-Jones James D. Marks Milan T. Tomic A Monoclonal Antibody Combination against both Serotypes A and B Botulinum Toxin Prevents Inhalational Botulism in a Guinea Pig Model Toxins botulinum neurotoxin aerosol monoclonal antibody guinea pig inhalation model oligoclonal antibody botulism |
| title | A Monoclonal Antibody Combination against both Serotypes A and B Botulinum Toxin Prevents Inhalational Botulism in a Guinea Pig Model |
| title_full | A Monoclonal Antibody Combination against both Serotypes A and B Botulinum Toxin Prevents Inhalational Botulism in a Guinea Pig Model |
| title_fullStr | A Monoclonal Antibody Combination against both Serotypes A and B Botulinum Toxin Prevents Inhalational Botulism in a Guinea Pig Model |
| title_full_unstemmed | A Monoclonal Antibody Combination against both Serotypes A and B Botulinum Toxin Prevents Inhalational Botulism in a Guinea Pig Model |
| title_short | A Monoclonal Antibody Combination against both Serotypes A and B Botulinum Toxin Prevents Inhalational Botulism in a Guinea Pig Model |
| title_sort | monoclonal antibody combination against both serotypes a and b botulinum toxin prevents inhalational botulism in a guinea pig model |
| topic | botulinum neurotoxin aerosol monoclonal antibody guinea pig inhalation model oligoclonal antibody botulism |
| url | https://www.mdpi.com/2072-6651/13/1/31 |
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