High-dose Recombinant Canarypox Vaccine Expressing HIV-1 Protein, in Seronegative Human Subjects

J Infect Dis. 2005 Oct 1;192(7):1249-59. doi: 10.1086/432915. Epub 2005 Aug 31.

Abstract

Background: In clinical trials, canarypox ALVAC-human immunodeficiency virus (HIV) vaccines have been shown to elicit human HIV-specific cytotoxic T lymphocyte (CTL) responses in some but not all healthy uninfected adults.Methods. A clinical trial was conducted to examine whether the vaccine vCP1452 would elicit a greater HIV-specific CTL response when given at a dose of 10(8.0) TCID50 (60 participants) than when given at the regular dose, 10(7.26) TCID50 (40 participants); as a control, a placebo vaccine preparation also was administered (10 participants).

Results: Two weeks after the last vaccination in a series, HIV-specific CTL responses were not significantly different when measured by either chromium-release assay (8% and 16% in the high- and regular-dose recipients, respectively) or interferon- gamma ELISpot assay (8% and 15% in the high- and regular-dose recipients, respectively); moreover, recipients of the higher dose had greater local and systemic reactions (P<.001).

Conclusions: High reactogenicity associated with an increased dose of vCP1452 negates the need for further evaluation of this strategy to boost the frequency of HIV-specific CTL response in seronegative human subjects. Development of highly immunogenic canarypox vectors requires further work to optimize vector and insert design, as well as novel ways to increase dosage and to reduce reactogenicity.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • AIDS Vaccines / administration & dosage*
  • AIDS Vaccines / genetics
  • AIDS Vaccines / immunology
  • Double-Blind Method
  • Female
  • HIV Antibodies / blood
  • HIV Seronegativity / immunology*
  • HIV-1 / immunology
  • Humans
  • Interferon-gamma / metabolism
  • Male
  • Recombinant Proteins / immunology*
  • Recombinant Proteins / metabolism
  • T-Lymphocytes, Cytotoxic / immunology*
  • Treatment Outcome
  • Vaccination
  • Vaccines, Synthetic / administration & dosage*
  • Vaccines, Synthetic / immunology
  • Viral Proteins / genetics
  • Viral Proteins / immunology
  • Viral Proteins / metabolism*

Substances

  • AIDS Vaccines
  • ALVAC-HIV vCP1452
  • HIV Antibodies
  • Recombinant Proteins
  • Vaccines, Synthetic
  • Viral Proteins
  • Interferon-gamma