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)

作者：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

来源：PLos One, 2011, 6(8): e21225.

DOI：10.1371/journal.pone.0021225

Background: 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.
Methods: 480 participants were evenly randomized to receive either: DNA (4 mg IM by Biojector) at 0, 1 and 2 months, followed by rAd5 (10(10) 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.
Results: The vaccine was well tolerated and safe. T-cell responses, detected by interferon-gamma (IFN-gamma) 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 seronegative 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.
Conclusion: The vaccine regimen was well-tolerated and induced polyfunctional CD4+ and CD8+ T-cells and multi-clade anti-Env binding antibodies.

• 出版日期2011-8-3