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Infection and Immunity, March 2003, p. 1491-1496, Vol. 71, No. 3
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.3.1491-1496.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Venezuelan Equine Encephalitis Virus-Vectored Vaccines Protect Mice against Anthrax Spore Challenge

John S. Lee,1* Angela G. Hadjipanayis,1 and Susan L. Welkos2

Virology Division,1 Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland2

Received 5 September 2002/ Returned for modification 22 October 2002/ Accepted 15 November 2002

Anthrax, a disease usually associated with herbivores, is caused by the bacterium Bacillus anthracis. The current vaccine licensed for human use requires a six-dose primary series and yearly boosters and causes reactogenicity in up to 30% of vaccine recipients. A minimally reactogenic vaccine requiring fewer inoculations is warranted. Venezuelan equine encephalitis (VEE) virus has been configured for use as a vaccine vector for a wide variety of immunogens. The VEE vaccine vector is composed of a self-replicating RNA (replicon) containing all of the VEE virus nonstructural genes and a multiple-cloning site in place of the VEE structural genes. Four different anthrax vaccines were constructed by cloning the protective antigen (PA) gene from B. anthracis into the VEE vaccine vector. The anthrax vaccines were produced by assembling the vectors into propagation-deficient VEE replicon particles in vitro. A/J mice inoculated subcutaneously with three doses of the mature 83-kDa PA vaccine were completely protected from challenge with the Sterne strain of B. anthracis. Similar results were obtained with vaccines composed of the PA gene fused to either the B. anthracis secretory sequence or to a tissue plasminogen activator secretory sequence in three additional mouse strains. Mice were unprotected from challenge after inoculation with the carboxy-terminal 63-kDa PA vaccine. These results suggest that these VEE-vectored vaccines may be suitable as candidate vaccines against anthrax.

* Corresponding author. Mailing address: Virology Division, USAMRIID, Fort Detrick, Frederick, MD 21702. Phone: (301) 619-4912. Fax: (301) 619-2290. E-mail: John.Lee{at}det.amedd.army.mil.

Editor: D. L. Burns

Infection and Immunity, March 2003, p. 1491-1496, Vol. 71, No. 3
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.3.1491-1496.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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