Aventis and Merck & Co. Inc announced that human trials have begun to test the safety and immune responses generated by using a combination of two anti-HIV-1 vaccine candidates in a complementary way.

The collaborative Phase I study looks at a prime-boost regimen that in an earlier preclinical investigation in monkeys found a higher level of immune response against HIV-1 than either vaccine used separately. Phase I represents the earliest stage of human testing for a potential vaccine.

The prime-boost regimen uses Merck's replication-defective adenovirus type 5 vector (Ad5) vaccine candidate first, followed by the canarypox virus vector (ALVAC) vaccine candidate from Aventis Pasteur, the vaccines business of Aventis. Data presented earlier this year at the 2003 Keystone Conference on HIV Vaccine Development demonstrated that the combination stimulated levels of cellular immune responses against HIV-1 that were higher than levels seen using the Ad5 vaccine candidate alone in a study of monkeys. The Phase I study will determine if a similar synergistic immune response can be generated in humans.

The study will include 17 sites across the United States. Volunteers participating in the study have received Merck's Ad5 vaccine candidate in previous clinical trials. In this study, they will receive a boost regimen of Aventis Pasteur's ALVAC vaccine candidate. After receiving the boost vaccine candidate, volunteers will have blood drawn and analyzed to determine the level of cellular immune responses generated by the candidate vaccines.

In the preclinical studies, rhesus macaque monkeys were vaccinated with the Ad5 vaccine candidate and subsequently boosted with the Ad5 vaccine candidate again or, alternatively, with the ALVAC vaccine candidate. Use of the two different vaccine candidates resulted in immune responses that were superior to those seen using just the Ad5 vaccine candidate alone. Specifically, the superior results were obtained when the Ad5 vaccine candidate was used as the priming (first dose) vaccine and the ALVAC vaccine candidate was used as the booster (second dose) vaccine.