Safety and Immunogenicity of DNA and MVA HIV-1 Subtype C Vaccine Prime-Boost Regimens: A Phase I Randomised Trial in HIV-Uninfected Indian Volunteers

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

In VivoElectroporation of Minicircle DNA as a Novel Method of Vaccine Delivery To Enhance HIV-1-Specific Immune Responses

“…Due to its safety, flexibility, stability, and cost-effectiveness, DNA vaccination has entered into a variety of human clinical trials (7,40,41). Although a proof of concept was demonstrated in a recent trial conducted in Thailand, significant scientific obstacles remain in improving the antigen expression and developing an efficient and safe in vivo gene delivery system (42)(43)(44).…”

HIV Epidemic in Asia: Implications for HIV Vaccine and Other Prevention Trials

“…[134][135][136][137] HIV vaccine clinical development came to a halt and shifted to designing immunogens able to induce HIV-specific broadly neutralizing antibodies (www.iavi.org). The prioritization of trialrelated financial and healthcare provisions, including access to an efficacious vaccine posttrial, among MSM in India indicates the importance of trials providing such services, as well as the value of formative research in identifying key concerns among participating communities in resourcelimited settings.…”

Experiences in recruiting volunteers through community based initiatives in Phase-1 vaccine trials in India

“…In a span of 6 y, a total of 94 healthy volunteers were recruited in three phase I trials in India. 8,10,18 At Pune site, 30 and 16 enrollments made were in the first (AAV) and third (DNA-MVA prime boost) HIV vaccine trials by reaching out to 8349 and 5881 individuals respectively. At the Chennai site, 32 and 16 volunteers were recruited in the second (MVA) and third (DNA-MVA prime boost) HIV vaccine trials by approaching 13 920 and 14 080 respectively.…”

“…The safety data of all the three trials conducted in Pune and Chennai have already been published. [8][9][10] The processes followed and experiences gained while implementing various community based initiatives for recruitment of healthy volunteers during the three HIV vaccine trials in India are described.…”