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Accepted (AM)Open Access (License Unspecified), Open
Journal article
Localization of the sites and characterization of the mechanisms by which anti-light chain antibodies neutralize the actions of the botulinum holotoxin
Vaccine, v 27(19), pp 2616-2624
2009
PMID: 19428868
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The recombinant, catalytically active light chain of botulinum toxin type A was evaluated as a potential vaccine candidate. Previous studies have shown that the light chain can elicit protective immunity
in vivo. [Kiyatkin N, Maksymowych AB, Simpson LL. Induction of immune response by oral administration of recombinant botulinum toxin. Infect Immun 1997;65(11):4586–91], but the underlying basis for this observation was not determined. In the present study, antibodies directed against the light chain were shown to act at three different sites in the body to produce neutralization. Firstly, these antibodies acted to block toxin absorption into the body. This was demonstrated
in vitro, in studies on binding and transport of toxin across epithelial monolayers, and
in vivo, in studies on inhalation poisoning. Secondly, anti-light chain antibodies acted to promote clearance of toxin from the general circulation. This was demonstrated
in vivo in studies on toxin levels in blood and in parallel studies on toxin accumulation in liver and spleen. Finally, anti-light chain antibodies acted to protect cholinergic nerves from botulinum toxin action. This was demonstrated in two types of
in vitro assays: rate of paralysis of murine phrenic nerve-hemidiaphragm preparations and extent of binding to Neuro-
2a cells. When taken together, these data show that anti-light chain antibodies can evoke three layers of protection against botulinum toxin.
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Details
- Title
- Localization of the sites and characterization of the mechanisms by which anti-light chain antibodies neutralize the actions of the botulinum holotoxin
- Creators
- Tsuyoshi Takahashi - Jefferson CollegeSuresh G. Joshi - Drexel UniversityFetweh Al-Saleem - Jefferson CollegeDenise Ancharski - Jefferson CollegeAjay Singh - Jefferson CollegeZidoon Nasser - Jefferson CollegeLance L. Simpson - Jefferson College
- Publication Details
- Vaccine, v 27(19), pp 2616-2624
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000265735400015
- Scopus ID
- 2-s2.0-63449094093
- Other Identifier
- 991019167647104721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Immunology
- Medicine, Research & Experimental