21   Safety and Immunogenicity Study of vCP1452/rgp160 Therapeutic Vaccines in Patients Treated with HAART for Over Two Years.

X. Jin*¹, M. Ramanathan Jr.¹, S. Barsoum¹, G. Deschenes¹, L. Ba¹, J. Binley¹, A. Hurley¹, R. El Habib², P. Caudrelierl², L. Zhang¹, D. D. Ho¹, and M. Markowitz¹.
¹Aaron Diamond AIDS Res. Ctr., The Rockefeller Univ., New York, NY and²Aventis, Lyon, France.

Background:To examine whether immune responses can be adequately boosted in patients on prolonged HAART, we conducted a safety and immunogenicity study using vCP1452, a recombinant canarypox vaccine carrying HIV-1 genes (gag, pol, env and nef), together with recombinant gp160.

Methods:Fourteen individuals treated within 90 days of primary infection and whose plasma viremia had been suppressed to undetectable levels by HAART for >2 years were enrolled. While continuing antiretroviral therapy, each subject received four intramuscular injections (days 0, 30, 90 and 180) of vCP1452 plus recombinant gp160.

Results:No significant adverse effects were observed except for mild transient tenderness at ALVAC injection sites. All patients have 2- to 3-log increases in anti-gp120 or anti-p24 antibody titers post vaccination. T-helper- cell activity, as assessed by lymphocyte proliferation to gp160 and p24, increased in six individuals, but the responses were not sustained. HIV-specific CD8⁺T cells were quantified before and after each vaccination, using intracellular cytokine staining for gamma-interferon after specific stimulation using viral antigens. Six patients had increases in CD8⁺T cells specific for more than one viral antigens, two patients had increases in CD8⁺T cells specific for a single HIV antigen, four patients had no detectable CD8 responses, and such analyses are in progress for two other patients.

Conclusions:In summary, vaccination with vCP1452 and recombinant gp160 is safe and immunogenic in this cohort of newly HIV-1-infected patients on effective antiretroviral therapy. The immunogenicity data will be correlated with the virologic outcome in twelve patients who will have already stopped therapy post vaccination.