Details

Autor(en) / Beteiligte

• 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
• Gray, Clive M.

Titel

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)

Ist Teil von

• PloS one, 2011-08, Vol.6 (8), p.e21225

Ort / Verlag

United States: Public Library of Science

Erscheinungsjahr

2011

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• 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.