AEGiS-14IAC: Preclinical immunogenicity of a multiprotein DNA/MVA vaccine for HIV-1.

14th International AIDS Conference

Barcelona, Spain - July 7-12, 2002

Preclinical immunogenicity of a multiprotein DNA/MVA vaccine for HIV-1.

Int Conf AIDS 2002 Jul 7-12; 14:(abstract no.. TuOrA1224)

Smith JM, Amara RR, Sharma S, Patel M, Earl P, Wyatt L, Moss B, Robinson HL
Yerkes Regional Primate Research Center, Emory University, Atlanta, GA, United States

BACKGROUND: Building on the success of preclinical trials using a DNA prime/MVA boost strategy in which protection from disease was achieved in the macaque/SHIV-89.6P model (Science 292:69), we have developed a DNA vaccine, pGA2/JS2, expressing HIV-1 Gag, Pr, RT, Env, Tat, Rev and Vpu from a single DNA. Plasmid GA2/JS2 is to be used in conjunction with a matched recombinant Modified Vaccinia Ankara vector, MVA/HIV-48, expressing Gag, Pol and Env, in a prime-boost protocol as a human vaccine for AIDS.

METHODS: Macaques were primed i.m. with either 3.0 mg or 0.3 mg of pGA2/JS2 DNA at weeks 0 and 8. All animals were boosted i.m. at week 24 with 1x108 pfu of MVA/HIV-48, with a control group receiving MVA/HIV-48 only. Cellular immune responses were tested using IFN-γ ELISPOTs and intracellular cytokine staining (ICC) following stimulation of PBMCs with pools of overlapping peptides for subtype B and an AG recombinant.

RESULTS: The frequency and breadth of the ELISPOT and ICC responses were similar to those in our successful SHIV trial. The DNA inoculations raised only low levels of cellular responses that were strongly boosted by the rMVA. One week post the rMVA the geometric mean frequencies of total ELISPOTs per million PBMC for the clade B pools were 905 in the 3 mg and 1148 in the 0.3mg DNA-primed groups. At this time, the rMVA-only group had a geometric mean frequency of 3 ELISPOTs per million PBMC. ICC analyses revealed averages of 1.3 % of total CD4 and 2.3 % of total CD8 responding to the clade B immunogen in the high dose DNA primed group, and averages of 0.68% and 0.88% of total CD4 and CD8 cells responding in the low dose DNA-primed group. The cellular immune response was focused on Gag and Env and had excellent breadth against the clade AG Gag peptides.

CONCLUSIONS: The DNA/MVA multiprotein vaccine elicited both a strong and broad cellular immune response to Gag and Env following priming with both 0.3 and 3.0 mg doses of DNA.

Keywords: AEGIS, HIV-1, Simian Acquired Immunodeficiency Syndrome, HIV Antibodies, Vaccines, DNA, HIV Infections, HIV Envelope Protein gp120, HIV, CD8-Positive T-Lymphocytes, Acquired Immunodeficiency Syndrome, HIV Core Protein p24, Case-Control Studies, Human, immunology

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