Neutralizing Concentrations of Anti-Botulinum Toxin Antibodies Positively Correlate with Mouse Neutralization Assay Results in a Guinea Pig Model.

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.

• Authors: Milan T Tomic, Shauna Farr-Jones, Emily S Syar, Nancy Niemuth, Dean Kobs, Michael J Hackett, Yero Espinoza, Zacchary Martinez, Khanh Pham, Doris M Snow, James D Marks, Ronald R Cobb
• Journal: Toxins (Toxins (Basel)) Vol. 13 Issue 9 (09 21 2021) ISSN: 2072-6651 [Electronic] Switzerland
• PMID: 34564675 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Neutralizing
• Antitoxins
• Drug Combinations
• Botulinum Toxins

Topics

• Animals
• Antibodies, Monoclonal (immunology, therapeutic use)
• Antibodies, Neutralizing (immunology, therapeutic use)
• Antitoxins (immunology, therapeutic use)
• Botulinum Toxins (toxicity)
• Botulism (drug therapy)
• Clostridium botulinum (genetics)
• Disease Models, Animal
• Drug Combinations
• Guinea Pigs
• Mice
• Serogroup