Next Article in Journal
Emerging Roles of Aryl Hydrocarbon Receptors in the Altered Clearance of Drugs during Chronic Kidney Disease
Previous Article in Journal
Cholera Toxin Encapsulated within Several Vibrio cholerae O1 Serotype Inaba Outer Membrane Vesicles Lacks a Functional B-Subunit
Article Menu
Issue 4 (April) cover image

Export Article

Open AccessArticle

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

1
Research and Development, Ology Bioservices, Inc., 626 Bancroft Way, Suite D, Berkeley, CA 94710, USA
2
Ology Bioservices, Alachua, FL 32615, USA
3
PRISM Program Office, Medical Countermeasures Systems, Ft. Detrick, MD 21702, USA
4
Vaccines and Therapeutics Division, Chemical and Biological Office, Ft. Detrick, MD 21702, USA
5
Battelle Biomedical Research Center, West Jefferson, Columbus, OH 43162, USA
6
Department of Anesthesia and Perioperative Care, University of California, 1001 Potrero Ave., San Francisco, CA 94110, USA
*
Author to whom correspondence should be addressed.
Toxins 2019, 11(4), 208; https://doi.org/10.3390/toxins11040208
Received: 22 February 2019 / Revised: 29 March 2019 / Accepted: 30 March 2019 / Published: 6 April 2019
(This article belongs to the Section Bacterial Toxins)
  |  
PDF [1432 KB, uploaded 6 April 2019]
  |  

Abstract

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. View Full-Text
Keywords: botulinum neurotoxin; aerosol; monoclonal antibody; guinea pig inhalation model; oligoclonal antibody; inhalational botulism; botulism botulinum neurotoxin; aerosol; monoclonal antibody; guinea pig inhalation model; oligoclonal antibody; inhalational botulism; botulism
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material

SciFeed

Share & Cite This Article

MDPI and ACS Style

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.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Toxins EISSN 2072-6651 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top