Monoclonal Antibody Combinations Prevent Serotype A and Serotype B Inhalational Botulism in a Guinea Pig Model

Toxins

DeanJ. Kobs¹  EmilyS. Syar¹  Nancy Niemuth¹  Shauna Farr-Jones²  JamesD. Marks²  RonaldR. Cobb³  DorisM. Snow³  ChristopherG. Earnhart⁴  Khanh Pham⁵  Zachary Martinez⁵  MilanT. Tomic⁵  Yero Espinoza⁵  Traci Pals⁶ 

[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;Ology Bioservices, Alachua, FL 32615, USA;PRISM Program Office, Medical Countermeasures Systems, Ft. Detrick, MD 21702, USA;Research and Development, Ology Bioservices, Inc., 626 Bancroft Way, Suite D, Berkeley, CA 94710, USA;Vaccines and Therapeutics Division, Chemical and Biological Office, Ft. Detrick, MD 21702, USA;

关键词: botulinum neurotoxin;    aerosol;    monoclonal antibody;    guinea pig inhalation model;    oligoclonal antibody;    inhalational botulism;    botulism;   

DOI  :  10.3390/toxins11040208

来源: DOAJ

【 摘 要 】

Botulinum neurotoxins (BoNT) are some of the most toxic proteins known, with a human LD₅₀ of ~1 ng/kg. Equine antitoxin has a half-life in circulation of less than 1 day and is limited to a treatment rather than a prevention indication. The development of monoclonal antibodies (mAbs) may represent an alternative therapeutic option that can be produced at high quantities and of high quality and with half-lives of >10 days. Two different three mAb combinations are being developed that specifically neutralize BoNT serotypes A (BoNT/A) and B (BoNT/B). We investigated the pharmacokinetics of the anti-BoNT/A and anti-BoNT/B antibodies in guinea pigs (Cavia porcellus) and their ability to protect guinea pigs against an aerosol challenge of BoNT/A1 or BoNT/B1. Each antibody exhibited dose-dependent exposure and reached maximum circulating concentrations within 48 h post intraperitoneal or intramuscular injection. A single intramuscular dose of the three mAb combination protected guinea pigs against an aerosol challenge dose of 93 LD₅₀ of BoNT/A1 and 116 LD₅₀ of BoNT/B1 at 48 h post antibody administration. These mAbs are effective in preventing botulism after an aerosol challenge of BoNT/A1 and BoNT/B1 and may represent an alternative to vaccination to prevent type A or B botulism in those at risk of BoNT exposure.

【 授权许可】

Unknown