View All Abstracts for Session 59
322 Cytotoxic T-Lymphocyte Responses in Volunteers Enrolled in a Phase I/II HIV-1 Prime-Boost Trial in Thailand
M. de Souza*1, C. Karnasuta1, J. Cox2, S. Gurunathan3, W. Heyward4, D. Birx2, J. Mc Neil2, A. Brown1, P. Pittisuttithum5, S. Nitayaphan1, and the TAVEG 6
1Armed Forces Res. Inst. of Med. Sci., Bangkok, Thailand; 2US Military Res. Program, Rockville, MD, USA; 3Aventis-Pasteur, Swiftwater, PA, USA; 4VaxGen, Inc., Brisbane, CA, USA; 5Vaccine Trial Ctr., Bangkok, Thailand; and 6Thai AIDS Vaccine Evaluation Group, Bangkok, Thailand
Background: To determine the frequency of cytotoxic T-lymphocyte (CTL) responses in HIV seronegative recipients of canarypox (ALVAC-vCP1521) and HIV recombinant bivalent gp120 (AIDSVAX B/E) as a boost.
Methods:The injection regimen was 0, 1, 3, and 6 months. Five subjects were initially enrolled in a phase I study to assess the safety of ALVAC-vCP1521 (Aventis Pasteur, Lyon, France), live recombinant canarypox-expressing HIV subtype E Env and B Gag/Pro. Volunteers were randomly assigned into 3 groups for phase II. Group A (n = 30) received placebo. Groups B and C received ALVAC-vCP1521. Group 2 (n = 45) received a boost of 200 mug of AIDSVAX B/E (VaxGen, Inc., Brisbane, USA) at 3 and 6 months. Group 3 (n = 45) received 600 mug of AIDSVAX B/E at 3 and 6 months. CTL assays were conducted at baseline, 1.5, 3.5, 6.5, 9, and 12 months for both phase I and phase II participants. Freshly isolated peripheral blood mononuclear cells were stimulated in vitro with HIV antigens and used as effectors in a standard chromium release assay with autologous EBV-transformed B cells infected with recombinant vaccinia viruses expressing clade E Env and clade B Gag/Pro antigens as targets.
Results: Two of 5 participants enrolled in the phase I study demonstrated CTL activity to HIV Env following the second injection. To date, CTL assays at 3 and 6 months following the fourth injection are ongoing and analysis is still blinded for the phase II component. CTL assays conducted at baseline on 124 volunteers were uniformly negative. Positive CTL responses were observed as early as 2 weeks following the second injection. Post-fourth injection, CTL responses increased to 16/116 subjects. CTL responses were observed to both Env and Gag/Pro antigens.
Conclusions: ALVAC-vCP1521 induces CTL activity against HIV Env and Gag vaccine antigens as early as post-second injection, prior to the protein boost. vCP1521 may be a potential phase III vaccine candidate.
Contact Author about this Abstract
