Subtype AE HIV-1 DNA and recombinant Fowlpoxvirus vaccines encoding five shared HIV-1 genes: safety and T cell immunogenicity in macaques

Vaccine. 2005 Mar 14;23(16):1949-56. doi: 10.1016/j.vaccine.2004.10.012.

Abstract

To induce broad T cell immunity to HIV-1, we evaluated the safety, immunogenicity and dose-response relationship of DNA and recombinant Fowlpoxvirus (rFPV) vaccines encoding five shared HIV subtype AE genes (Gag, Pol, Env, Tat, Rev) in pigtail macaques. The DNA (three doses of either 1 mg or 4.5 mg) and rFPV (a single boost of either 5 x 10(7) or 2 x 10(8) plaque forming units) vaccines were administered intramuscularly without adjuvants. Broadly reactive HIV-specific T cell immunity was stimulated by all doses of the vaccines administered, without significant differences between the high and low doses studied. The vaccines induced both CD4 and CD8 T cell responses to Gag, Pol, Env and Tat/Rev proteins, with CD4 T cell responses being greater in magnitude than CD8 T cell responses. The vaccine-induced T cell responses had significant cross-recognition of heterologous HIV-1 proteins from non-AE HIV-1 subtypes. In conclusion, these subtype AE HIV-1 DNA and rFPV vaccines were safe, induced broad T-cell immunity in macaques, and are suitable for progression into clinical trials.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • AIDS Vaccines / immunology*
  • Animals
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Cytokines / biosynthesis
  • DNA, Viral / immunology*
  • Dose-Response Relationship, Immunologic
  • Fowlpox virus / immunology*
  • Genes, Viral / genetics
  • HIV Antibodies / analysis
  • HIV Antibodies / biosynthesis
  • HIV-1 / genetics
  • HIV-1 / immunology*
  • Immunity, Cellular
  • Interferon-gamma / biosynthesis
  • Macaca nemestrina
  • Phenotype
  • T-Lymphocytes / immunology*
  • Vaccines, Conjugate / immunology
  • Vaccines, Synthetic / immunology
  • Viral Vaccines / immunology*

Substances

  • AIDS Vaccines
  • Cytokines
  • DNA, Viral
  • HIV Antibodies
  • Vaccines, Conjugate
  • Vaccines, Synthetic
  • Viral Vaccines
  • Interferon-gamma