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) |
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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 NIAID HIV Vaccine Trials Network |
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Affiliation: | Aurum Institute for Health Research, Klerksdorp, South Africa. |
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Abstract: | BackgroundThe 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.Methods480 participants were evenly randomized to receive either: DNA (4 mg IM by Biojector) at 0, 1 and 2 months, followed by rAd5 (1010 PU IM 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.ResultsThe 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.ConclusionThe vaccine regimen was well-tolerated and induced polyfunctional CD4+ and CD8+ T-cells and multi-clade anti-Env binding antibodies.Trial Registration:ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00125970","term_id":"NCT00125970"}}NCT00125970 |
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