Monoclonal Antibody Combinations Prevent Serotype A and Serotype B Inhalational Botulism in a Guinea Pig Model
AbstractBotulinum 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. View Full-Text
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Tomic, M.T.; Espinoza, Y.; Martinez, Z.; Pham, K.; Cobb, R.R.; Snow, D.M.; Earnhart, C.G.; Pals, T.; Syar, E.S.; Niemuth, N.; Kobs, D.J.; Farr-Jones, S.; Marks, J.D. Monoclonal Antibody Combinations Prevent Serotype A and Serotype B Inhalational Botulism in a Guinea Pig Model. Toxins 2019, 11, 208.
Tomic MT, Espinoza Y, Martinez Z, Pham K, Cobb RR, Snow DM, Earnhart CG, Pals T, Syar ES, Niemuth N, Kobs DJ, Farr-Jones S, Marks JD. Monoclonal Antibody Combinations Prevent Serotype A and Serotype B Inhalational Botulism in a Guinea Pig Model. Toxins. 2019; 11(4):208.Chicago/Turabian Style
Tomic, Milan T.; Espinoza, Yero; Martinez, Zachary; Pham, Khanh; Cobb, Ronald R.; Snow, Doris M.; Earnhart, Christopher G.; Pals, Traci; Syar, Emily S.; Niemuth, Nancy; Kobs, Dean J.; Farr-Jones, Shauna; Marks, James D. 2019. "Monoclonal Antibody Combinations Prevent Serotype A and Serotype B Inhalational Botulism in a Guinea Pig Model." Toxins 11, no. 4: 208.
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