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

• Published in: PloS one Vol. 8; no. 2; p. e55831
• Main Authors: Mehendale, Sanjay, Thakar, Madhuri, Sahay, Seema, Kumar, Makesh, Shete, Ashwini, Sathyamurthi, Pattabiraman, Verma, Amita, Kurle, Swarali, Shrotri, Aparna, Gilmour, Jill, Goyal, Rajat, Dally, Len, Sayeed, Eddy, Zachariah, Devika, Ackland, James, Kochhar, Sonali, Cox, Josephine H, Excler, Jean-Louis, Kumaraswami, Vasanthapuram, Paranjape, Ramesh, Ramanathan, Vadakkuppatu Devasenapathi
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 13-02-2013; Public Library of Science (PLoS)
• Subjects: Acquired immune deficiency syndrome; Adenoviruses; Adult; AIDS; AIDS vaccines; AIDS Vaccines - adverse effects; AIDS Vaccines - immunology; Antibodies; Antibodies, Neutralizing; Clinical trials; Deoxyribonucleic acid; DNA; DNA vaccines; Double-Blind Method; Drug therapy; Enzyme-linked immunosorbent assay; Follow-Up Studies; Gag protein; Genes; Glycoprotein gp160; HIV; HIV Antibodies - immunology; HIV Infections - prevention & control; HIV-1 - immunology; Homology; Human immunodeficiency virus; Humans; Immune response; Immunogenicity; India; Interferon; Laboratories; Medicine; Nef protein; Neutralizing; Priming; Product development; Proteins; Randomization; Safety; Tat protein; Treatment Outcome; Tuberculosis; Vaccination; Vaccines; Vaccines, DNA - immunology; Vaccinia - prevention & control; Vaccinia virus - immunology; Vectors (Biology); Viral Vaccines - adverse effects; Viral Vaccines - immunology; Viruses; γ-Interferon; India; New York
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0055831

A randomized, double-blind, placebo controlled phase I trial.
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.
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-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 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-γELISPOT responses between the groups at 3, 6 and 9 months post-last vaccination.
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.
Clinical Trial Registry CTRI/2009/091/000051.