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

Toxins

Emily S. Syar¹  Michael J. Hackett¹  Dean Kobs¹  Nancy Niemuth¹  Shauna Farr-Jones²  James D. Marks²  Ronald R. Cobb³  Doris M. Snow³  Milan T. Tomic⁴  Khanh Pham⁴  Yero Espinoza⁴  Zacchary Martinez⁴ 

[1] Battelle Biomedical Research Center, West Jefferson, Columbus, OH 43162, USA;Department of Anesthesia and Perioperative Care, University of California, 1001 Potrero Ave., San Francisco, CA 94110, USA;National Resilience, Inc., 13200 NW, Nano Ct, Alachua, FL 32615, USA;National Resilience, Inc., 2061 Challenger Dr., Alameda, CA 94501, USA;

关键词: botulinum neurotoxin;    botulism;    aerosol;    monoclonal antibody (mAb);    guinea pig inhalation model;    oligoclonal antibody;   

DOI  :  10.3390/toxins13090671

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown