PLoS ONE (Jan 2012)

A phase I double blind, placebo-controlled, randomized study of a multigenic HIV-1 adenovirus subtype 35 vector vaccine in healthy uninfected adults.

  • Michael C Keefer,
  • Jill Gilmour,
  • Peter Hayes,
  • Dilbinder Gill,
  • Jakub Kopycinski,
  • Hannah Cheeseman,
  • Michelle Cashin-Cox,
  • Marloes Naarding,
  • Lorna Clark,
  • Natalia Fernandez,
  • Catherine A Bunce,
  • Christine M Hay,
  • Sabrina Welsh,
  • Wendy Komaroff,
  • Lottie Hachaambwa,
  • Tony Tarragona-Fiol,
  • Eddy Sayeed,
  • Devika Zachariah,
  • James Ackland,
  • Kelley Loughran,
  • Burc Barin,
  • Emmanuel Cormier,
  • Josephine H Cox,
  • Patricia Fast,
  • Jean-Louis Excler

DOI
https://doi.org/10.1371/journal.pone.0041936
Journal volume & issue
Vol. 7, no. 8
p. e41936

Abstract

Read online

We conducted a phase I, randomized, double-blind, placebo-controlled trial to assess the safety and immunogenicity of escalating doses of two recombinant replication defective adenovirus serotype 35 (Ad35) vectors containing gag, reverse transcriptase, integrase and nef (Ad35-GRIN) and env (Ad35-ENV), both derived from HIV-1 subtype A isolates. The trial enrolled 56 healthy HIV-uninfected adults.Ad35-GRIN/ENV (Ad35-GRIN and Ad35-ENV mixed in the same vial in equal proportions) or Ad35-GRIN was administered intramuscularly at 0 and 6 months. Participants were randomized to receive either vaccine or placebo (10/4 per group, respectively) within one of four dosage groups: Ad35-GRIN/ENV 2×10(9) (A), 2×10(10) (B), 2×10(11) (C), or Ad35-GRIN 1×10(10) (D) viral particles.No vaccine-related serious adverse event was reported. Reactogenicity events reported were dose-dependent, mostly mild or moderate, some severe in Group C volunteers, all transient and resolving spontaneously. IFN-γ ELISPOT responses to any vaccine antigen were detected in 50, 56, 70 and 90% after the first vaccination, and in 75, 100, 88 and 86% of Groups A-D vaccine recipients after the second vaccination, respectively. The median spot forming cells (SFC) per 10(6) PBMC to any antigen was 78-139 across Groups A-C and 158-174 in Group D, after each of the vaccinations with a maximum of 2991 SFC. Four to five HIV proteins were commonly recognized across all the groups and over multiple timepoints. CD4+ and CD8+ T-cell responses were polyfunctional. Env antibodies were detected in all Group A-C vaccinees and Gag antibodies in most vaccinees after the second immunization. Ad35 neutralizing titers remained low after the second vaccination.Ad35-GRIN/ENV reactogenicity was dose-related. HIV-specific cellular and humoral responses were seen in the majority of volunteers immunized with Ad35-GRIN/ENV or Ad35-GRIN and increased after the second vaccination. T-cell responses were broad and polyfunctional.ClinicalTrials.gov NCT00851383.