Safety and immunogenicity of DNA and MVA HIV-1 subtype C vaccine prime-boost regimens: A phase I randomized trial in HIV-uninfected Indian volunteers.

Mehendale, S.; Thakar, M.; Sahay, S.; Kumar, M.; Shete, A.; Sathyamurthi, P.; Verma, A.; Kurle, S.; Shrotri, A.; Gilmour, J.; Goyal, R.; Dally, L.; Sayeed, E.; Zachariah, D.; Ackland, J.; Kochhar, S.; Cox, J.H.; Excler, J.L.; Kumaraswami, V.; Paranjape, R.; Ramanathan, V.D.

PLoS One; 2013; 8; e55831.

Abstract: Study Design: A randomized, double-blind, placebo controlled phase I trial.

Methods: The 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.

Results: Both 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- g ELISPOT responses were directed mostly to Env and Gag proteins. Although the IFN- g ELISPOT responses were infrequent after ADVAX vaccinations, the response rate was significantly higher in group A after 1 st and 2 nd 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- c ELISPOT responses between the groups at 3, 6 and 9 months post-last vaccination.

Conclusions: Although DNA priming resulted in enhancement of immune responses after 1 st MVA boosting, the overall DNA prime MVA boost was not found to be immunologically superior to homologous MVA boosting.

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