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Clin. Vaccine Immunol. doi:10.1128/CVI.00402-07
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Detoxified lethal toxin as a potential mucosal vaccine against anthrax

Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Box 672, 601 Elmwood Avenue, Rochester, New York 14642, USA

^* To whom correspondence should be addressed. Email: Mingtao_Zeng{at}urmc.rochester.edu.

	Abstract

The nontoxic mutant lethal factor (mLF/E687C) and functional protective antigen (PA63) of Bacillus anthracis were evaluated as mucosal vaccines against anthrax in A/J mice. Three-time intranasal vaccination with 30 µg of mLF or 60 µg of PA63 elicited significant serum and mucosal antibody responses, with the anthrax lethal toxin neutralizing titers of 40 and 60 in immune sera, respectively. However, only 30% and 60% of the vaccinated animals in the two groups could survive from the challenge with 100 x LD₅₀ of B. anthracis Sterne spores, respectively. In contrast, three-time vaccination with the combination of 30 µg of mLF and 60 µg of PA63, the detoxified lethal toxin, elicited significantly higher antibody responses against LF and PA than vaccination using the individual mLF or PA63 with the same dose and schedule. Vaccination with the detoxified lethal toxin resulted in significant higher lethal toxin neutralizing antibody titers in sera (90). Animals vaccinated with 3 doses of the detoxified lethal toxin were completely protected against the spore challenge. The data suggested that mLF and PA63 have a mutual enhancement effect for evoking systemic and mucosal immune responses and the detoxified lethal toxin can be used as an efficient mucosal vaccine against anthrax.