Background: Canarypox ALVAC-HIV vaccine (vCP1452) elicits HIV-1 specific CD8⁺ T-cell responses when given to healthy uninfected adults; however, only a minority of participants (ppts) has had detectable responses in prior vaccine trials. We hypothesized that increasing the dose of vCP1452 would result in a greater frequency of HIV-1 specific CD8⁺ T-cell responses among vaccinated adults.

Methods: We immunized 110 ppts with vCP1452 at a dose of 10^8.0TCID₅₀ (60), 10^7.26 TCID₅₀ (40), or placebo (10) at days 0, 28, 84, and 168. Immunizations were given with vCP1452 reconstituted in 4.8ml of sterile water or 0.9% NaCl delivered via injection into both vastus lateralis muscles (2.4ml in each) of ppts at 0, 1, 3, and 6 months. Safety was evaluated by routine history and physical examinations in addition to laboratory safety analyses on ppts blood. HIV-1 specific CD8⁺ T-cell responses were measured by analyzing peripheral blood mononuclear cells using the overnight IFN-g ELISpot and 2-week ⁵¹Cr-release assays.

Results: Overall, 91% of the ppts receiving vCP1452 (10⁸ or 10^7.26 dose) had local reactions while 85% had systemic symptoms. Although the final 2 immunizations were better tolerated than the initial 2 (p < 0.05), ppts receiving the 10^8.0 dose had greater local (78%) and systemic (83%) reactions of ≥ moderate intensity when compared with those receiving the 10^7.26 dose (45% for local and 43% systemic, p < 0.05). Fourteen (14; 13%) ppts did not receive all of their immunizations, which was due to vaccine related side effects in 8 ppts (7%). The immunizations were better tolerated among ppts ≥ 40 years of age, and there were no differences in vaccine side effects when comparing gender and race. HIV-1 specific CD8⁺ T-cell responses were detectable as measured by the 2 separate assays. However, after 4 immunizations, there were no significant differences in the frequency of Gag/Env specific CD8⁺ T-cells responses elicited by 2 vaccine doses. This was true whether the responses to the 10⁸ or 10^7.26 dose were measured by the IFN-g ELISpot (18% vs 24%, respectively) or ⁵¹Cr-release (9% vs 12%, respectively) assays.

Conclusions: Our results demonstrate that the 10⁸ dose of vCP1452 is associated with a concomitantly greater reactogenicity profile without eliciting increased HIV-1 specific CD8⁺ T-cell responses. These data clearly demonstrate that the use of a higher dose of vCP1452 than what is currently being used in clinical trials is not warranted.