[TuOrA1226] HIV-specific Cytotoxic T Lymphocyte (CTL) response in seronegative Ugandan volunteers vaccinated with HIV-ALVAC vCP 205: result of the phase I HIVNET 007 vaccine study

14th International AIDS Conference

Barcelona, Spain — July 7-12, 2002

[TITLE:] HIV-specific Cytotoxic T Lymphocyte (CTL) response in seronegative Ugandan volunteers vaccinated with HIV-ALVAC vCP 205: result of the phase I HIVNET 007 vaccine study

[AUTHOR(S):] H. Cao¹, P Kaleebu², J Flores³, R El-Habib⁴, R Salata⁵, E Mbidde⁶, P Mugyenyi⁷, J Ellner⁸, R Mugerwa⁹

Int Conf AIDS. 2002 Jul 7-12;14:Abstract No. TuOrA1226

BACKGROUND: This first preventative HIV-1 vaccine study in Africa aimed to evaluate the safety and immunogenicity of the ALVAC-HIV vCP205 in seronegative Ugandan volunteers. The vaccine construct was a live recombinant canarypox vector expressing HIV-1 gp120 (MN), the anchoring region of gp41 (LAI), the entire gag and a portion of the pol.

METHODS: Forty low risk individuals were randomized to receive the vCP205 (n=20), ALVAC RG RABIES (n=10) or placebo (n=10) in a double-blinded fashion at months 0, 1, 3 and 6. HIV-specific cellular immune responses were assessed after each immunization, and at months 9 and 18. We report here the CTL responses elicited by this clade B-based immunogen in a geographic region where clade A and D viruses predominate.

RESULTS: Freshly isolated PBMCs were stimulated in vitro with clade B antigens and tested for cytolytic activity using target cells infected with recombinant vaccinia viruses expressing clade A, B and D Gag and Env antigens in the standard chromium release assay. Confirmatory assays with the ELISpot assay were done using cryopreserved PBMCs with overlapping synthetic peptides. Immunogenicity to vCP205 was detected in this study population. The Gag- and Env-specific cumulative response was 40% and 35% respectively, using the Elispot assay, compared to 10% (both Gag and Env) in the standard chromium release assay. HIV-specific activity to clade A and D antigens was also demonstrated, suggesting that vCP205 elicited cross-clade T cell response. Epitope mapping in thevaccine responders identified immmunogenic regions corresponding to known epitopes previously described in HIV-1 infection.

CONCLUSIONS: We have demonstrated that HIV-1-specific CTL responses can be elicited by a clade B ALVAC HIV-1 vaccine in an African population where clades A and D predominate. This study has established the feasibility of conducting vaccine trials in Africa and has transferred sophisticated laboratory analysis on-site.

Presenting author: H. Cao

1CA Dept Health Services, CA DHS, VRDL, 850 Marina Bay Parkway, Richmond, CA 94112, United States.

2Uganda Virus Research Institute, Entebbe, Uganda.

3NIAID, Bethesda, United States.

4Aventis Pasteur, Marcy l'Etoile, France.

5Case Western Reserve University, Cleveland, United States.

6Makerere University, Kampala, Uganda.

7Joint Clinical Research Center, Kampala, Uganda.

8University of Medicine and Dentisty of New Jersey, Newark, United States.

9Makere University, Kampala, United States.

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