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Journal of Virology, July 2001, p. 6107-6114, Vol. 75, No. 13
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.13.6107-6114.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Rearrangement of the Genes of Vesicular Stomatitis Virus Eliminates Clinical Disease in the Natural Host: New Strategy for Vaccine Development

E. Brian Flanagan,1 Joann M. Zamparo,2 L. Andrew Ball,1 Luis L. Rodriguez,2,* and Gail W. Wertz1

Department of Microbiology, University of Alabama School of Medicine, Birmingham, Alabama 35294,1 and Plum Island Animal Disease Center, Agricultural Research Service, U.S. Department of Agriculture, Greenport, New York 119442

Received 22 December 2000/Accepted 28 March 2001

Gene expression among the nonsegmented negative-strand RNA viruses is controlled by distance from the single transcriptional promoter, so the phenotypes of these viruses can be systematically manipulated by gene rearrangement. We examined the potential of gene rearrangement as a means to develop live attenuated vaccine candidates against Vesicular stomatitis virus (VSV) in domestic swine, a natural host for this virus. The results showed that moving the nucleocapsid protein gene away from the single transcriptional promoter attenuated and ultimately eliminated the potential of the virus to cause disease. Combining this change with relocation of the surface glycoprotein gene yielded a vaccine that protected against challenge with wild-type VSV. By incremental manipulation of viral properties, gene rearrangement provides a new approach to generating live attenuated vaccines against this class of virus.

* Corresponding author. Mailing address: Plum Island Animal Disease Center, Agricultural Research Service, USDA, P.O. Box 848, Greenport, NY 11944-0848. Phone: (631) 323-3364. Fax: (631) 323-2507. E-mail: lrodriguez{at}piadc.ars.usda.gov.

Journal of Virology, July 2001, p. 6107-6114, Vol. 75, No. 13
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.13.6107-6114.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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