Attenuated Vesicular Stomatitis Viruses as Vaccine Vectors

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Journal of Virology, May 1999, p. 3723-3732, Vol. 73, No. 5
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Attenuated Vesicular Stomatitis Viruses as Vaccine Vectors

Anjeanette Roberts, Linda Buonocore, Ryan Price, John Forman, and John K. Rose^*

Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06510

Received 6 October 1998/Accepted 26 January 1999

We showed previously that a single intranasal vaccination of mice with a recombinant vesicular stomatitis virus (VSV) expressingan influenza virus hemagglutinin (HA) protein provided completeprotection from lethal challenge with influenza virus (A. Roberts,E. Kretzschmar, A. S. Perkins, J. Forman, R. Price, L. Buonocore,Y. Kawaoka, and J. K. Rose, J. Virol. 72:4704-4711, 1998). Becausesome pathogenesis was associated with the vector itself, in thepresent study we generated new VSV vectors expressing HA whichare completely attenuated for pathogenesis in the mouse model.The first vector has a truncation of the cytoplasmic domain ofthe VSV G protein and expresses influenza virus HA (CT1-HA). Thisnonpathogenic vector provides complete protection from lethalinfluenza virus challenge after intranasal administration. A secondvector with VSV G deleted and expressing HA ( $Delta$ G-HA) is also protectiveand nonpathogenic and has the advantage of not inducing neutralizingantibodies to the vectoritself.

^* Corresponding author. Mailing address: Department of Pathology, Yale University School of Medicine, New Haven, CT 06510. Phone:(203) 785-6794. Fax: (203) 785-7467. E-mail: jrose{at}biomed.med.yale.edu.

Journal of Virology, May 1999, p. 3723-3732, Vol. 73, No. 5
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

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