Abstract:
The recombinant vaccine, tgAAC09, based on an adeno-associated virus serotype 2 (AAV2) vector encoding
HIV-1 subtype C Gag, protease, and part of reverse transcriptase, induced robust T cell and antibody responses
in nonhuman primates. In a previous phase I study in 80 healthy HIV-seronegative European and Indian
adults, the vaccine was generally safe, well tolerated, and modestly immunogenic when administered once at
doses up to 3 1011 DRP. This phase II double-blind, randomized, placebo-controlled trial tested two administrations
and a higher dosage of tgAAC009. Ninety-one healthy HIV-seronegative adults from three African
countries were given one of three dosage levels of tgAAC09 (3 1010, 3 1011, or 3 1012 DRP) intramuscularly,
either at a 6- or 12-month interval; follow-up was 18 months. Overall, 65% and 57% of vaccine recipients
experienced local and systemic signs and symptoms, respectively, most being mild. Frequency and severity
were not dose related and were similar to those in placebo recipients. No vaccine-related serious adverse events
were reported. Overall, HIV-specific T cell responses were detected by IFN-g ELISPOT in 17/69 (25%) vaccine
recipients with 38% (10/26) responders in the highest dosage group. The response rate improved significantly
with boosting at 6, but not 12 months, in the 3 1011 and 3 1012 dosage groups only. Neutralizing antibody
titers to the AAV2 did not alter the frequency of immune responses to HIV. Two doses of tgAAC09 were well
tolerated at the dosage levels given. Fewer than half the recipients of the highest vaccine dosage, 3 1012 DRP,
had T cell responses to HIV.
