PLoS ONE (Jan 2011)

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).

  • 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,
  • NIAID HIV Vaccine Trials Network

DOI
https://doi.org/10.1371/journal.pone.0021225
Journal volume & issue
Vol. 6, no. 8
p. e21225

Abstract

Read online

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.