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A Phase 1 Study to Evaluate the Safety and Immunogenicity of a Recombinant HIV Type 1 Subtype C Adeno-Associated Virus Vaccine

2008; Mary Ann Liebert, Inc.; Volume: 24; Issue: 6 Linguagem: Inglês

10.1089/aid.2007.0292

1931-8405

Sanjay Mehendale, Jan van Lunzen, Nathan Clumeck, Jürgen K. Rockstroh, Eva Vets, Philip R. Johnson, Pervin Anklesaria, Burc Barin, Mark Boaz, Sonali Kochhar, Jennifer Lehrman, Claudia Schmidt, Mathieu Peeters, Carolynne Schwarze‐Zander, Kabamba Kabeya, Tobias Glaunsinger, Seema Sahay, Madhuri Thakar, Ramesh Paranjape, Jill Gilmour, Jean‐Louis Excler, Patricia Fast, Alison E. Heald,

Virology and Viral Diseases

A novel prophylactic AIDS vaccine candidate, consisting of single-stranded DNA for HIV-1 subtype C gag, protease, and part of reverse transcriptase genes, enclosed within a recombinant adeno-associated virus serotype-2 protein capsid (tgAAC09) induced T cell responses and antibodies in nonhuman primates. In this randomized, dose escalation phase I trial, HIV-uninfected healthy volunteers (50 in Europe, 30 in India) received a single intramuscular injection of tgAAC09 at 3 × 109 DNase resistant particles (DRP) (n = 16), 3 × 1010 DRP (n = 23), 3 × 1011 DRP (n = 25), or placebo (n = 16). Twenty-one participants in Europe received a second (boost) dose of 3 × 1011 DRP tgAAC09 or placebo at least 24 weeks after the first injection. The vaccine was safe and well-tolerated after initial and boost vaccination. Local and systemic reactogenicity was experienced by 13–25% of participants and was not dose related. No vaccine-related serious adverse events were reported. Modest HIV-specific T cell responses were detected in 7/64 vaccinees (40–385 SFC/106 PBMC), with 16% (4/25) responders in the highest dose group. All responses were to Gag epitopes. tgAAC09 appears to be safe, well-tolerated, and modestly immunogenic. Further evaluation of higher doses of tgAAC09 and boost injections is ongoing in Africa.