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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


Journal Article

Mehendale, S.; van Lunzen, J.; Clumeck, N.; Rockstroh, J.; Vets, E.; Johnson, P.R.; Anklesaria, P.; Barin, B.; Boaz, M.; Kochhar, S.; Lehrman, J.; Schmidt, C.; Peeters, M.; Schwarze-Zander, C.; Kabamba, K.; Glaunsinger, T.; Sahay, S.; Thakar, M.; , ; Heald, A.

AIDS Research and Human Retroviruses




Adolescent; Adult; AIDS Vaccines; Antibody Formation; Capsid; Dependovirus; DNA- Viral; Double-Blind Method; Female; HIV Infections; HIV-1; Immunity- Cellular; Immunization- Secondary; Injections- Intramuscular; Interferon-gamma; Male; Middle Aged

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 x 10(9) DNase resistant particles (DRP) (n = 16), 3 x 10(10) DRP (n = 23), 3 x 10(11) DRP (n = 25), or placebo (n = 16). Twenty-one participants in Europe received a second (boost) dose of 3 x 10(11) 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/10(6) 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.

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