A Phase IIA Randomized Clinical Trial of a Multiclade HIV-1 DNA Prime Followed by a Multiclade rAd5 HIV-1 Vaccine Boost in Healthy Adults (HVTN204)

• DOI: 10.1371/journal.pone.0021225
• Publication Date: 2011-08-03T20:49:32Z
• Authors: Gavin J. Churchyard; Cecilia Morgan; Elizabeth Adams; John Hural; Barney S. Graham; Zoe Moodie; Doug Grove; Glenda Gray; Linda-Gail Bekker; M. Juliana McElrath; Georgia D. Tomaras; Paul Goepfert; Spyros Kalams; Lindsey R. Baden; Michelle Lally; Raphael Dolin; William Blattner; Artur Kalichman; J. Peter Figueroa; Jean Pape; Mauro Schechter; Olivier Defawe; Stephen C. De Rosa; David C. Montefiori; Gary J. Nabel; Lawrence Corey; Michael C. Keefer
• Keywords: Adult; Male; 0301 basic medicine; Adolescent; Science; T-Lymphocytes; Human Immunodeficiency Virus Proteins; T cells; Immunization, Secondary; Cytotoxic T cells; Enzyme-Linked Immunosorbent Assay; Antibodies, Viral; Antibodies; Adenoviridae; Cohort Studies; Interferon-gamma; 03 medical and health sciences; Vaccines, DNA; Humans; Enzyme-linked immunoassays; AIDS Vaccines; Vaccines; Q; R; Anemia; Middle Aged; 16. Peace & justice; 3. Good health; Immunoglobulin G; Antibody response; HIV-1; Cytokines; Medicine; Female; Immunization; Research Article

The safety and immunogenicity of a vaccine regimen consisting of a 6-plasmid HIV-1 DNA prime (envA, envB, envC, gagB, polB, nefB) boosted by a recombinant adenovirus serotype-5 (rAd5) HIV-1 with matching inserts was evaluated in HIV-seronegative participants from South Africa, United States, Latin America and the Caribbean.480 participants were evenly randomized to receive either: DNA (4 mg i.m. by Biojector) at 0, 1 and 2 months, followed by rAd5 (10(10) PU i.m. by needle/syringe) at 6 months; or placebo. Participants were monitored for reactogenicity and adverse events throughout the 12-month study. Peak and duration of HIV-specific humoral and cellular immune responses were evaluated after the prime and boost.The vaccine was well tolerated and safe. T-cell responses, detected by interferon-γ (IFN-γ) ELISpot to global potential T-cell epitopes (PTEs) were observed in 70.8% (136/192) of vaccine recipients overall, most frequently to Gag (54.7%) and to Env (54.2%). In U.S. vaccine recipients T-cell responses were less frequent in Ad5 sero-positive versus sero-negative vaccine recipients (62.5% versus 85.7% respectively, p = 0.035). The frequency of HIV-specific CD4+ and CD8+ T-cell responses detected by intracellular cytokine staining were similar (41.8% and 47.2% respectively) and most secreted ≥2 cytokines. The vaccine induced a high frequency (83.7%-94.6%) of binding antibody responses to consensus Group M, and Clades A, B and C gp140 Env oligomers. Antibody responses to Gag were elicited in 46% of vaccine recipients.The vaccine regimen was well-tolerated and induced polyfunctional CD4+ and CD8+ T-cells and multi-clade anti-Env binding antibodies.ClinicalTrials.gov NCT00125970.