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)

• Published in: PloS one Vol. 6; no. 8; p. e21225
• Main Authors: Churchyard, Gavin J, Morgan, Cecilia, Adams, Elizabeth, Hural, John, Graham, Barney S, Moodie, Zoe, Grove, Doug, Gray, Glenda, Bekker, Linda-Gail, McElrath, M Juliana, Tomaras, Georgia D, Goepfert, Paul, Kalams, Spyros, Baden, Lindsey R, Lally, Michelle, Dolin, Raphael, Blattner, William, Kalichman, Artur, Figueroa, J Peter, Pape, Jean, Schechter, Mauro, Defawe, Olivier, De Rosa, Stephen C, Montefiori, David C, Nabel, Gary J, Corey, Lawrence, Keefer, Michael C
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 03.08.2011; Public Library of Science (PLoS)
• Subjects: Acquired immune deficiency syndrome; Adenoviridae - genetics; Adenoviruses; Adolescent; Adult; Adults; AIDS; AIDS vaccines; AIDS Vaccines - administration & dosage; AIDS Vaccines - immunology; Anemia - chemically induced; Antibodies; Antibodies, Viral - blood; Antibodies, Viral - immunology; Antigenic determinants; Binding; Biological response modifiers; Biology; Cancer; CD4 antigen; CD8 antigen; Clinical trials; Cohort Studies; Cytokines; Deoxyribonucleic acid; Disease prevention; DNA; env Gene Products, Human Immunodeficiency Virus - genetics; env Gene Products, Human Immunodeficiency Virus - immunology; Enzyme-Linked Immunosorbent Assay; Epidemiology; Epitopes; Female; gag Gene Products, Human Immunodeficiency Virus - genetics; gag Gene Products, Human Immunodeficiency Virus - immunology; Health care; HIV; HIV-1 - genetics; HIV-1 - immunology; Hospitals; Human immunodeficiency virus; Human Immunodeficiency Virus Proteins - genetics; Human Immunodeficiency Virus Proteins - immunology; Humans; Immune response (cell-mediated); Immune response (humoral); Immunization - adverse effects; Immunization - methods; Immunization, Secondary - adverse effects; Immunization, Secondary - methods; Immunogenicity; Immunoglobulin G - blood; Immunoglobulin G - immunology; Immunoglobulins; Immunotherapy; Infections; Infectious diseases; Inserts; Interferon; Interferon-gamma - blood; Interferon-gamma - immunology; Lymphocytes T; Male; Medical research; Medicine; Middle Aged; nef Gene Products, Human Immunodeficiency Virus - genetics; nef Gene Products, Human Immunodeficiency Virus - immunology; Oligomers; pol Gene Products, Human Immunodeficiency Virus - genetics; pol Gene Products, Human Immunodeficiency Virus - immunology; Product development; T cells; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Vaccines; Vaccines, DNA - administration & dosage; Vaccines, DNA - immunology; Young Adult; γ-Interferon; North Carolina; Haiti; Rio de Janeiro Brazil; United States > US; Massachusetts; Brazil; South Africa; Jamaica; Thailand; Maryland
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0021225

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.