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321 ALVAC-HIV (vCP205) + Oligomeric gp160MN/LAI-2 Prime-Boost in 91 HIV-Seronegative Adults: Summary of Safety and Immunogenicity Data
J. Kim*1, J. Cox2, S. Ratto-Kim2, T. VanCott2, N. Michael1, R. El Habib3, M. Klein3, B. Gilliam2, D. Birx1, J. McNeil1, and M. Robb1
1Walter Reed Army Inst. of Res., Washington, DC, USA; 2Henry M. Jackson Fndn., Rockville, MD, USA; and 3Aventis-Pasteur, Lyon, France
Background:Prime-boost strategies in the context of HIV vaccine development use combinations of immunogens to improve B- and T-cell responses. Here we describe the safety and immunogenicity of ALVAC-HIV prime (vCP205) with an oligomeric subunit boost (gp160MN/LAI-2).
Study Design: Vaccine(s) were administered at 0, 4, 12, and 24 weeks. In part A, 4 open label groups of 5 volunteers received escalating doses of oligomeric gp160. In part B, 6 randomized, double-blind groups of 12 volunteers (10 active/2 placebo) received varying doses and schedules of vCP205/gp160.
Results: Ninety-one persons completed the study. At day 196 (post fourth vaccination), 84% of persons were HIV EIA positive; 65% were Western-blot positive. All were negative at day 0. Forty-five of 51 (88%) developed antibody to gp160MN; 44% (16/36) recipients of vCP205 had Ab to p24 versus 0/19 gp160 (only) recipients. Forty-six percent (29/63) of volunteers showed gp160MN-specific lymphoproliferation (LSI >5); 14% (9/63) had a cross-proliferative response to gp160TH023 (R5, subtype E). The day-336 cumulative CD8+ CTL rate is 28.3% (17 of 60, specific lysis >10% at 2 E:T ratios, 8 time points); statistically consistent with cumulative CTL results from other trials utilizing this vector. Preliminary data comparing day 0 to day 182 (post fourth vaccination) show 74% (65/87) had NAb against MN but only 17% had NAb against IIIB (>50% reduction in HIV p24 expression in pre- vs. post-vaccination sera). Among primary isolates BZ167 (X4R5,B) and US1 (R5,B), there was >50% neutralization in 48 and 7%, respectively. There was occasional neutralization of the primary isolates CM237 (R5, B) and US4 (R5, B). Fifty-one percent neutralized the adapted primary isolate US1 "G."
Conclusions: vCP205 and oligomeric gp160MN/LAI-2 are immunogenic. The combination yields false positive WB in 65% of recipients. CD4 proliferative responses and CTL generation are statistically consistent with previous trials of vCP205+gp120. NAb to the homologous HIVMN are identified in most volunteers, and some have NAb capable of neutralizing R5-using primary isolates.
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