A phase 1/2 study of a multiclade HIV-1 DNA plasmid prime and recombinant adenovirus serotype 5 boost vaccine in HIV-Uninfected East Africans (RV 172)

J Infect Dis. 2010 Feb 15;201(4):600-7. doi: 10.1086/650299.

Abstract

Background: Human immunodeficiency virus (HIV) vaccine development remains a global priority. We describe the safety and immunogenicity of a multiclade DNA vaccine prime with a replication-defective recombinant adenovirus serotype 5 (rAd5) boost.

Methods: The vaccine is a 6-plasmid mixture encoding HIV envelope (env) subtypes A, B, and C and subtype B gag, pol, and nef, and an rAd5 expressing identical genes, with the exception of nef. Three hundred and twenty-four participants were randomized to receive placebo (n=138), a single dose of rAd5 at 10(10) (n = 24) or 10(11) particle units (n = 24), or DNA at 0, 1, and 2 months, followed by rAd5 at either 10(10) (n= 114) or 10(11) particle units (n = 24) boosting at 6 months. Participants were followed up for 24 weeks after the final vaccination.

Results: The vaccine was safe and well tolerated. HIV-specific T cell responses were detected in 63% of vaccinees. Titers of preexisting Ad5 neutralizing antibody did not affect the frequency and magnitude of T cell responses in prime-boost recipients but did affect the response rates in participants that received rAd5 alone (P = .037).

Conclusion: The DNA/rAd5 vaccination regimen was safe and induced HIV type 1 multi-clade T cell responses, which were not significantly affected by titers of preexisting rAd5 neutralizing antibody. Trial Registration. ClinicalTrials.gov identifier: NCT00123968 .

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • AIDS Vaccines / administration & dosage*
  • AIDS Vaccines / adverse effects
  • AIDS Vaccines / genetics
  • AIDS Vaccines / immunology
  • Adenoviridae / genetics
  • Adenoviridae / immunology*
  • Adolescent
  • Adult
  • Africa, Eastern
  • Antibodies, Neutralizing / blood
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / blood
  • Antibodies, Viral / immunology
  • Antigens, Viral / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Cells, Cultured
  • DNA, Viral / genetics
  • DNA, Viral / immunology*
  • Double-Blind Method
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • HIV Infections / immunology
  • HIV Infections / prevention & control*
  • HIV-1 / genetics
  • HIV-1 / immunology*
  • Human Immunodeficiency Virus Proteins / genetics
  • Human Immunodeficiency Virus Proteins / immunology
  • Humans
  • Interferon-gamma / metabolism
  • Leukocytes, Mononuclear / immunology
  • Male
  • Middle Aged
  • Plasmids / genetics
  • Plasmids / immunology*
  • Vaccines, DNA / administration & dosage*
  • Vaccines, DNA / adverse effects
  • Vaccines, DNA / genetics
  • Vaccines, DNA / immunology
  • Young Adult

Substances

  • AIDS Vaccines
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Antigens, Viral
  • DNA, Viral
  • Human Immunodeficiency Virus Proteins
  • Vaccines, DNA
  • Interferon-gamma

Associated data

  • ClinicalTrials.gov/NCT00123968