1. Neutralizing Concentrations of Anti-Botulinum Toxin Antibodies Positively Correlate with Mouse Neutralization Assay Results in a Guinea Pig Model.
- Author
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Tomic, Milan T, Farr-Jones, Shauna, Syar, Emily S, Niemuth, Nancy, Kobs, Dean, Hackett, Michael J, Espinoza, Yero, Martinez, Zacchary, Pham, Khanh, Snow, Doris M, Marks, James D, and Cobb, Ronald R
- Subjects
aerosol ,botulinum neurotoxin ,botulism ,guinea pig inhalation model ,monoclonal antibody ,mouse neutralization assay ,neutralizing antibody concentration ,oligoclonal antibody ,Biodefense ,Foodborne Illness ,Rare Diseases ,Emerging Infectious Diseases ,Infectious Diseases ,Vaccine Related ,Biotechnology ,Prevention ,Immunization ,Orphan Drug ,Biochemistry and Cell Biology ,Pharmacology and Pharmaceutical Sciences - Abstract
Botulinum neurotoxins (BoNT) are some of the most toxic proteins known and can induce respiratory failure requiring long-term intensive care. Treatment of botulism includes the administration of antitoxins. Monoclonal antibodies (mAbs) hold considerable promise as BoNT therapeutics and prophylactics, due to their potency and safety. A three-mAb combination has been developed that specifically neutralizes BoNT serotype A (BoNT/A), and a separate three mAb combination has been developed that specifically neutralizes BoNT serotype B (BoNT/B). A six mAb cocktail, designated G03-52-01, has been developed that combines the anti-BoNT/A and anti-BoNT/B mAbs. The pharmacokinetics and neutralizing antibody concentration (NAC) of G03-52-01 has been determined in guinea pigs, and these parameters were correlated with protection against an inhalation challenge of BoNT/A1 or BoNT/B1. Previously, it was shown that each antibody demonstrated a dose-dependent mAb serum concentration and reached maximum circulating concentrations within 48 h after intramuscular (IM) or intraperitoneal (IP) injection and that a single IM injection of G03-52-01 administered 48 h pre-exposure protected guinea pigs against an inhalation challenge of up to 93 LD50s of BoNT/A1 and 116 LD50s of BoNT/B1. The data presented here advance our understanding of the relationship of the neutralizing NAC to the measured circulating antibody concentration and provide additional support that a single IM or intravenous (IV) administration of G03-52-01 will provide pre-exposure prophylaxis against botulism from an aerosol exposure of BoNT/A and BoNT/B.
- Published
- 2021