A Monoclonal Antibody Combination against both Serotypes A and B Botulinum Toxin Prevents Inhalational Botulism in a Guinea Pig Model
Open Access
- 5 January 2021
- Vol. 13 (1), 31
- https://doi.org/10.3390/toxins13010031
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
This publication has 49 references indexed in Scilit:
- Analysis of the Mechanisms That Underlie Absorption of Botulinum Toxin by the Inhalation RouteInfection and Immunity, 2012
- Advanced Development of the rF1V and rBV A/B Vaccines: Progress and ChallengesAdvances in Preventive Medicine, 2011
- Identification of the Factors That Govern the Ability of Therapeutic Antibodies to Provide Postchallenge Protection Against Botulinum Toxin: A Model for Assessing Postchallenge Efficacy of Medical Countermeasures against Agents of Bioterrorism and Biological WarfareThe Journal of pharmacology and experimental therapeutics, 2011
- Botulinum neurotoxin neutralizing activity of immune globulin (IG) purified from clinical volunteers vaccinated with recombinant botulinum vaccine (rBV A/B)Vaccine, 2010
- Use of botulinum toxin in the neurology clinicNature Reviews Neurology, 2010
- Inhalational Botulism in Rhesus Macaques Exposed to Botulinum Neurotoxin Complex Serotypes A1 and B1Clinical and Vaccine Immunology, 2010
- Fake Botox, Real ThreatScientific American, 2010
- Human Botulism Immune Globulin for the Treatment of Infant BotulismThe New England Journal of Medicine, 2006
- Sequence homology and structural analysis of the clostridial neurotoxinsJournal of Molecular Biology, 1999
- Therapeutic Uses of Botulinum ToxinThe New England Journal of Medicine, 1991