AEGiS-15IAC: Efficacy of DNA and fowlpoxvirus prime/boost vaccines for HIV-1 and SHIV.

15th International AIDS Conference

Bangkok, Thailand - July 11-16, 2004

Efficacy of DNA and fowlpoxvirus prime/boost vaccines for HIV-1 and SHIV.

Int Conf AIDS 2004 Jul 11-16; 15:(abstract no. ThOrA1345)

De Rose R, Dale CJ, Stratov I, Chea S, Purcell DF, Ramshaw IA, Thomson S, Boyle DB, Coupar B, Ramsay AJ, Ffrench R, Law M, Emery S, Cooper DA, Kent SJ
University of Melbourne, Melbourne, Australia

BACKGROUND: DNA/poxvirus prime/boost HIV vaccine regimens have generally proven superior to other regimens in the induction of high-level HIV-specific T cell responses. We analysed optimised HIV-1 subtype B and SHIV DNA and Fowlpoxvirus (FPV) vaccines for the induction of protective immunity. The number of vaccinations required and the effect of cytokine (IFNgamma or IL-12) co-expression in the FPV boost was also studied.

METHODS: 60 macaques (6/group) were vaccinated IM with DNA vaccines expressing modified gag, pol, env, tat, rev and vpu of HIV-1 or SHIV and optimised for primate CpG content (1 mg twice) and boosted with FPV expressing modified gag, pol and env (5 x 10[7] pfu). Comparator groups were boosted with FPV co-expressing either IFNgamma or IL-12, administered FPV or DNA alone, or given only 1 DNA prime. Animals were challenged with either non-pathogenic HIV-1 or pathogenic SHIV[229].

RESULTS: DNA/FPV regimens induced high levels of functional T cells by IFNgamma ELISpot (Mean 1005 SFC/10[6] PBMC to inactivated SIV). Intracellular IFNgamma staining, proliferation, and epitope mapping studies demonstrated a coordinated induction of broad CD4+ and CD8+ T cell immunity (mean CD4 responses 1.0%, CD8 responses 3.4%). Immunogenicity of comparator groups was inferior. Significant protection against SHIV challenge was demonstrated (mean VL reduction 1.5 log at peak and 1.3 log at set point). Protection was consistent with immunogenicity across groups, with the exception that the regimen of three DNA vaccines alone induced similar protection to the DNA/FPV regimen.

CONCLUSIONS: An optimised set and schedule of DNA and FPV HIV-1 vaccines, suitable for proceeding into human clinical trials, are highly immunogenic and protective in macaques. Subtype A/E DNA and FPV vaccines with further expansions in antigen content, and the effect of dose, are currently being studied in preparation for expanded clinical trials in Thailand. Funding: NIH/NIAID contract N01AI05395

Keywords: AEGIS, HIV-1, Fowlpox virus, AIDS Vaccines, SIV, Genes, gag, Genes, pol, Genes, env, Gene Products, tat, Vaccines, DNA, HIV Antibodies, CD8-Positive T-Lymphocytes, HIV Infections, T-Lymphocytes, HIV, Vaccination, Thailand, Humans, genetics, immunology

040711
ThOrA1345