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)

PLoS One. 2011;6(8):e21225. doi: 10.1371/journal.pone.0021225. Epub 2011 Aug 3.

Abstract

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 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.

Results: 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.

Conclusion: The vaccine regimen was well-tolerated and induced polyfunctional CD4+ and CD8+ T-cells and multi-clade anti-Env binding antibodies.

Trial registration: ClinicalTrials.gov NCT00125970.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • AIDS Vaccines / administration & dosage
  • AIDS Vaccines / immunology*
  • Adenoviridae / genetics
  • Adolescent
  • Adult
  • Anemia / chemically induced
  • Antibodies, Viral / blood
  • Antibodies, Viral / immunology
  • Cohort Studies
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • HIV-1 / genetics
  • HIV-1 / immunology*
  • Human Immunodeficiency Virus Proteins / genetics
  • Human Immunodeficiency Virus Proteins / immunology*
  • Humans
  • Immunization / adverse effects
  • Immunization / methods
  • Immunization, Secondary / adverse effects
  • Immunization, Secondary / methods
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Interferon-gamma / blood
  • Interferon-gamma / immunology
  • Male
  • Middle Aged
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Vaccines, DNA / administration & dosage
  • Vaccines, DNA / immunology*
  • Young Adult
  • env Gene Products, Human Immunodeficiency Virus / genetics
  • env Gene Products, Human Immunodeficiency Virus / immunology
  • gag Gene Products, Human Immunodeficiency Virus / genetics
  • gag Gene Products, Human Immunodeficiency Virus / immunology
  • nef Gene Products, Human Immunodeficiency Virus / genetics
  • nef Gene Products, Human Immunodeficiency Virus / immunology
  • pol Gene Products, Human Immunodeficiency Virus / genetics
  • pol Gene Products, Human Immunodeficiency Virus / immunology

Substances

  • AIDS Vaccines
  • Antibodies, Viral
  • Human Immunodeficiency Virus Proteins
  • Immunoglobulin G
  • Vaccines, DNA
  • env Gene Products, Human Immunodeficiency Virus
  • gag Gene Products, Human Immunodeficiency Virus
  • nef Gene Products, Human Immunodeficiency Virus
  • nef protein, Human immunodeficiency virus 1
  • pol Gene Products, Human Immunodeficiency Virus
  • Interferon-gamma

Associated data

  • ClinicalTrials.gov/NCT00125970

Grant support