| Autor: |
Milan T. Tomic, Yero Espinoza, Zachary Martinez, Khanh Pham, Ronald R. Cobb, Doris M. Snow, Christopher G. Earnhart, Traci Pals, Emily S. Syar, Nancy Niemuth, Dean J. Kobs, Shauna Farr-Jones, James D. Marks |
| Jazyk: |
angličtina |
| Rok vydání: |
2019 |
| Předmět: |
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| Zdroj: |
Toxins, Vol 11, Iss 4, p 208 (2019) |
| Druh dokumentu: |
article |
| ISSN: |
2072-6651 |
| DOI: |
10.3390/toxins11040208 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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