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Journal of Virology, April 2004, p. 3930-3940, Vol. 78, No. 8
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.8.3930-3940.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Highly Effective Control of an AIDS Virus Challenge in Macaques by Using Vesicular Stomatitis Virus and Modified Vaccinia Virus Ankara Vaccine Vectors in a Single-Boost Protocol

Elizabeth Ramsburg,1 Nina F. Rose,1 Preston A. Marx,2 Megan Mefford,2 Douglas F. Nixon,3 Walter J. Moretto,3 David Montefiori,4 Patricia Earl,5 Bernard Moss,5 and John K. Rose1*

Yale University School of Medicine, New Haven, Connecticut,1 Tulane University Health Sciences Center, New Orleans, Louisiana,2 Gladstone Institute of Virology and Immunology, San Francisco, California,3 Duke University Medical Center, Durham, North Carolina,4 National Institute of Allergy and Infectious Diseases, Bethesda, Maryland5

Received 26 September 2003/ Accepted 22 December 2003

Previous studies have shown that vaccination and boosting of rhesus macaques with attenuated vesicular stomatitis virus (VSV) vectors encoding Env and Gag proteins of simian immunodeficiency virus-human immunodeficiency virus (SHIV) hybrid viruses protect rhesus macaques from AIDS after challenge with the highly pathogenic SHIV 89.6P (23). In the present study, we compared the effectiveness of a single prime-boost protocol consisting of VSV vectors expressing SHIV Env, Gag, and Pol proteins to that of a protocol consisting of a VSV vector prime followed with a single boost with modified vaccinia virus Ankara (MVA) expressing the same SHIV proteins. After challenge with SHIV 89.6P, MVA-boosted animals controlled peak challenge viral loads to less than 2 x 106 copies/ml (a level significantly lower than that seen with VSV-boosted animals and lower than those reported for other vaccine studies employing the same challenge). MVA-boosted animals have shown excellent preservation of CD4+ T cells, while two of four VSV-boosted animals have shown significant loss of CD4+ T cells. The improved protection in MVA-boosted animals correlates with trends toward stronger prechallenge CD8+-T-cell responses to SHIV antigens and stronger postchallenge SHIV-neutralizing antibody production.

* Corresponding author. Mailing address: Department of Pathology, Yale University School of Medicine, 310 Cedar St., New Haven, CT 06510. Phone: (203) 785-6795. Fax: (203) 785-7467. E-mail: john.rose{at}yale.edu.

Journal of Virology, April 2004, p. 3930-3940, Vol. 78, No. 8
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.8.3930-3940.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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