This Article Full Text (PDF) Other Versions of this Article: IAI.01025-07v1 76/3/1314    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Baldwin, M. R. Articles by Barbieri, J. T. Search for Related Content PubMed PubMed Citation Articles by Baldwin, M. R. Articles by Barbieri, J. T.

 Previous Article  |  Next Article 

Infect. Immun. doi:10.1128/IAI.01025-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

A subunit vaccine against the seven serotypes of botulism

Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, WI USA; Food Research Institute, University of Wisconsin at Madison, Madison, WI USA

^* To whom correspondence should be addressed. Email: jtb01{at}mcw.edu.

	Abstract

The botulinum neurotoxins (BoNTs) are the most toxic proteins for humans and are classified as category A toxins. There are seven serotypes of the BoNTs defined by the lack of cross serotype toxin neutralization. Thus, an effective vaccine must neutralize each BoNT serotype. The BoNTs are organized as di-chain A-B toxins, where the N-terminal domain (LC) is a zinc metalloprotease targeting SNARE proteins that is linked to the C-terminal domain (HC) by a disulfide bond. The HC comprises a translocation domain (HCT) and a C-terminal receptor binding domain (HCR). HCRs of the seven serotypes of the BoNTs (hepta-HCR) were engineered for expression in Escherichia coli, and each HCR was purified from E. coli lysates. Immunization of mice with the E. coli-derived hepta-serotype HCR vaccine elicited an antibody response to each of the seven BoNT HCRs and neutralized challenge by 10,000 LD₅₀ of each of the seven BoNTs serotypes. A solid phase assay showed that the anti-hepta-serotype HCR sera inhibited HCR/A and HCR/B binding to the ganglioside GT1b, the first step in BoNT intoxication of neurons. This is the first E. coli derived vaccine that effectively neutralizes each of the seven BoNT serotypes.

This article has been cited by other articles:

• Keller, J. E. (2008). Characterization of New Formalin-Detoxified Botulinum Neurotoxin Toxoids. CVI 15: 1374-1379 [Abstract] [Full Text]