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Journal of Virology, December 1998, p. 10180-10188, Vol. 72, No. 12
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Enhanced T-Cell Immunogenicity and Protective Efficacy of a Human Immunodeficiency Virus Type 1 Vaccine Regimen Consisting of Consecutive Priming with DNA and Boosting with Recombinant Fowlpox Virus

Stephen J. Kent,1,* Anne Zhao,1 Susan J. Best,2 Jenalle D. Chandler,1,3 David B. Boyle,4 and Ian A. Ramshaw5

AIDS Pathogenesis Research Unit, Macfarlane Burnet Centre for Medical Research, Fairfield 3078, Victoria,1 National Serology Reference Laboratory, Fitzroy 3065,2 Department of Microbiology and Immunology, Melbourne University, Parkville 3052, Victoria,3 CSIRO, Division of Animal Health, Australian Animal Health Laboratories, Geelong 3220, Victoria,4 and Division of Cell Biology and Immunology, John Curtin School for Medical Research, Australian National University, Canberra 2601, ACT,5 Australia

Received 29 May 1998/Accepted 20 August 1998

The induction of human immunodeficiency virus (HIV)-specific T-cell responses is widely seen as critical to the development of effective immunity to HIV type 1 (HIV-1). Plasmid DNA and recombinant fowlpox virus (rFPV) vaccines are among the most promising safe HIV-1 vaccine candidates. However, the immunity induced by either vaccine alone may be insufficient to provide durable protection against HIV-1 infection. We evaluated a consecutive immunization strategy involving priming with DNA and boosting with rFPV vaccines encoding common HIV-1 antigens. In mice, this approach induced greater HIV-1-specific immunity than either vector alone and protected mice from challenge with a recombinant vaccinia virus expressing HIV-1 antigens. In macaques, a dramatic boosting effect on DNA vaccine-primed HIV-1-specific helper and cytotoxic T-lymphocyte responses, but a decline in HIV-1 antibody titers, was observed following rFPV immunization. The vaccine regimen protected macaques from an intravenous HIV-1 challenge, with the resistance most likely mediated by T-cell responses. These studies suggest a safe strategy for the enhanced generation of T-cell-mediated protective immunity to HIV-1.

* Corresponding author. Mailing address: Macfarlane Burnet Centre for Medical Research, P. O. Box 254, Fairfield, Vic, 3078, Australia. Phone: 61392822175. Fax: 61394826152. E-mail: kent{at}burnet.edu.au.

Journal of Virology, December 1998, p. 10180-10188, Vol. 72, No. 12
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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