Abstract
Study DesignA randomized, double-blind, placebo controlled phase I trial.MethodsThe trial was conducted in 32 HIV-uninfected healthy volunteers to assess the safety and immunogenicity of prime-boost vaccination regimens with either 2 doses of ADVAX, a DNA vaccine containing Chinese HIV-1 subtype C env gp160, gag, pol and nef/tat genes, as a prime and 2 doses of TBC-M4, a recombinant MVA encoding Indian HIV-1 subtype C env gp160, gag, RT, rev, tat, and nef genes, as a boost in Group A or 3 doses of TBC-M4 alone in Group B participants. Out of 16 participants in each group, 12 received vaccine candidates and 4 received placebos.ResultsBoth vaccine regimens were found to be generally safe and well tolerated. The breadth of anti-HIV binding antibodies and the titres of anti-HIV neutralizing antibodies were significantly higher (p<0.05) in Group B volunteers at 14 days post last vaccination. Neutralizing antibodies were detected mainly against Tier-1 subtype B and C viruses. HIV-specific IFN-γ ELISPOT responses were directed mostly to Env and Gag proteins. Although the IFN-γ ELISPOT responses were infrequent after ADVAX vaccinations, the response rate was significantly higher in group A after 1st and 2nd MVA doses as compared to the responses in group B volunteers. However, the priming effect was short lasting leading to no difference in the frequency, breadth and magnitude of IFN-γELISPOT responses between the groups at 3, 6 and 9 months post-last vaccination.ConclusionsAlthough DNA priming resulted in enhancement of immune responses after 1st MVA boosting, the overall DNA prime MVA boost was not found to be immunologically superior to homologous MVA boosting.Trial RegistrationClinical Trial Registry CTRI/2009/091/000051
Highlights
A safe and efficacious HIV vaccine is urgently needed to curtail the HIV pandemic
For effective control of HIV/AIDS in India, an HIV vaccine may prove to be a useful addition to other available prevention options
The Associated Virus (AAV)-based vaccine showed poor immunogenicity, the Modified Vaccinia Ankara (MVA) HIV-1 subtype C vaccine induced a modest level of dose-dependent immune responses [2,3,4]
Summary
A safe and efficacious HIV vaccine is urgently needed to curtail the HIV pandemic. India is currently facing a burden of 2.39 million people living with HIV/AIDS, the estimated HIV prevalence in the adult population is only 0.31% [1]. For effective control of HIV/AIDS in India, an HIV vaccine may prove to be a useful addition to other available prevention options. Two phase I clinical HIV prophylactic vaccine trials have been conducted previously in India to evaluate Adenovirus-Associated Virus (AAV) and Modified Vaccinia Ankara (MVA) based HIV vaccines. The AAV-based vaccine showed poor immunogenicity, the MVA HIV-1 subtype C vaccine induced a modest level of dose-dependent immune responses [2,3,4]. Since vaccine strategies based on inducing neutralizing antibodies failed in large scale phase III trials [5,6] the direction of HIV prophylactic vaccine research shifted to evaluating vaccine candidates having the ability to induce cell-mediated immune responses. A higher magnitude and limited breadth of Tcell responses, as detected by Interferon-gamma (IFN-c) ELISPOT assays, did not correlate with protection in monkey models [7]
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