AIDSWEEKLY Plus; Monday, December 7, 1998
Daniel J. DeNoon, Senior Editor
Animals primed with a DNA vaccine encoding HIV-1 antigens and then boosted with a recombinant fowlpox virus (rFPV) vaccine expressing the same antigens were able to resist challenge. Protection appeared to be due to HIV-1 specific T-helper type 1 (Th1) immune responses.
"This study suggests a primary role for T-cell responses in protection from HIV-1 challenge," concluded Stephen J. Kent of the Macfarlane Burnet Center for Medical Research, Victoria, Australia, and colleagues.
Kent et al. reported their findings in the Journal of Virology ("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," J Virol, 1998;72(12):10180-8).
Many workers believe that an effective AIDS vaccine must stimulate Th1 responses and elicit strong cellular immune responses to HIV. DNA vaccines and recombinant viruses are considered particularly promising in this regard because they tend to elicit cellular rather than humoral immunity.
The DNA component of the vaccine used the plasmid pNL4.3dpol, which expresses the HIV-1[NL4.3] env and gag genes. The fowlpox component used rFPV containing the HIV-1[BH10] env gene.
Mice immunized with the DNA/rFPV prime/boost vaccine resisted challenge with recombinant vaccinia virus expressing HIV-1 antigens.
Macaque monkeys immunized with the vaccine were challenged with HIV-1[LAI]. The virus normally establishes only an acute infection before being cleared by T-cell responses. None of the four vaccinated animals, but all four unvaccinated controls, developed acute HIV infections. The vaccinated animals had much stronger HIV specific T cell responses than the control animals.
"Further enhancement of the breadth and strength of the HIV specific T-cell responses and abrogation of the antibody response by co-delivery of a Th1 cytokine together with the DNA- and rFPV-encoded vaccine antigens could determine whether T-cell responses alone can control primate lentivirus infections in vivo," Kent et al. wrote.
The researchers are currently evaluating the ability of this vaccine strategy to protect animals against more pathogenic lentiviral strains. They are hopeful that their approach will bear fruit.
"This combination vaccine strategy could represent the basis of a safe and effective HIV-1 vaccine," they suggested.
This work was supported by the National Health and Medical Research Council, Australia.
The corresponding author for this study is Stephen J. Kent, Macfarlane Burnet Centre for Medical Research, P.O. Box 254, Fairfield, Victoria 3078, Australia. Phone: 61392822175. Fax: 61394826152. Email: <kent@burnet.edu.au>.
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