AEGiS-13IAC: DNA and fowlpoxvirus (FPV) HIV vaccines - co-expression of interferon-gamma by FPV further boosts HIV-specific T cell responses.

13th International AIDS Conference

Durban, South Africa - July 9-July 14, 2000

DNA and fowlpoxvirus (FPV) HIV vaccines - co-expression of interferon-gamma by FPV further boosts HIV-specific T cell responses.

Int Conf AIDS 2000 Jul 9-14; 13:(abstract no. TuOrA290)

Kent S, Zhao A, Dale CJ, Land S, Boyle D, Ramshaw I
S. Kent, Macfarlane Burnet Centre, Yarra Bend Rd, Fairfield 3078, Australia, Tel.: +61 392 822 175, Fax: +61 394 826 152, E-mail: kent@burnet.edu.au

BACKGROUND: A preventive HIV vaccine would be a quantum advance on current efforts to control the HIV pandemic. While HIV protein vaccines have not shown encouraging efficacy and live attenuated vaccines are unsafe, both plasmid DNA and fowlpoxvirus (FPV) HIV vaccines can induce CTL responses in a proportion of outbred primates, although neither is particularly efficacious alone.

METHODS: A DNA/FPV prime/boost HIV-1 vaccine regimen has been studied in macaques and a rFPV expressing both HIV-1gag/pol and human interferon-g (FPVgag/pol-IFNg) was constructed and assessed for safety and ability to enhance HIV-primed T cells in macaques (M. nemestrina).

RESULTS: CTL and Th1 responses were dramatically enhanced in both mice and monkeys following DNA/FPV prime/boost regimens. High level CTL and Th responses to both Env and Gag proteins were observed in all studied monkeys following immunisation. Inoculation of DNA/FPV vaccinated animals with *100 monkey infectious doses of HIV-1 resulted in very rapid clearance of HIV-1, almost certainly mediated by HIV-specific CTL/Th1 responses. Recent studies have demonstrated that novel FPV vaccines co-expressing IFNg could be even more effective in boosting HIV-primed T cells. FPV gag/pol-IFNg vaccinations were safe and generated enhanced T cell proliferative responses (of a Th1 phenotype) to HIV antigens but not control tetanus antigens. Enhanced CTL responses to HIV antigens were also observed following FPVgag/pol-IFNg expressing vaccinations.

CONCLUSIONS: These observations suggest that priming with DNA vaccines and boosting with avipox co-expressing IFNg should induce unprecendented levels HIV-specific T cells and could be useful therapeutic or preventive HIV-1 vaccines. An urgent investment in moving these regimens through the clinical trials process could reap significant dividends to humanity.

Keywords: AEGIS, AIDS Vaccines, Fowlpox virus, T-Lymphocytes, Interferon Type II, HIV Infections, HIV-1, HIV Antigens, Vaccines, DNA, Gene Products, gag, HIV Seropositivity, Vaccination, Greece, Human, Animal, Mice, immunology
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