Comparison of whole gene and whole virus scrambled antigen approaches for DNA prime and fowlpox virus boost HIV type 1 vaccine regimens in macaques

AIDS Res Hum Retroviruses. 2005 Apr;21(4):292-300. doi: 10.1089/aid.2005.21.292.

Abstract

T cell immunity plays a critical role in controlling HIV-1 viremia, and encoding a limited set of HIV-1 genes within DNA and poxvirus vectors can, when used sequentially, induce high levels of T cell immunity in primates. However, a limited breadth of T cell immunity exposes the host to potential infection with either genetically diverse HIV-1 strains or T cell escape variants of HIV-1. In an attempt to induce maximally broad immunity, we examined DNA and recombinant fowlpox virus (rFPV) vaccines encoding all HIV-1 genes derived from a global HIV-1 consensus sequence, but expressed as multiple overlapping scrambled 30-amino acid segments (scrambled antigen vaccines, or SAVINEs). Three groups of seven pigtail macaques were immunized with sets of DNA and rFPV expressing Gag/Pol antigens only, the whole genome SAVINE antigens, or no HIV-1 antigens and T cell immunity was monitored by ELISpot and intracellular cytokine staining. High levels of cross-subtype HIV-specific T cell immunity to Gag were consistently induced in the seven macaques primed with DNA and rFPV vaccines expressing Gag/Pol as intact proteins. It was, however, difficult to repeatedly boost immunity with further rFPV immunizations, presumably reflecting high levels of anti- FPV immunity. Unfortunately, this vaccine study did not consistently achieve a broadened level of T cell immunity to multiple HIV genes utilizing the novel whole-virus SAVINE approach, with only one of seven immunized animals generating broad T cell immunity to multiple HIV-1 proteins. Further refinements are planned with alternative vector strategies to evaluate the potential of the SAVINE technology.

Publication types

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

MeSH terms

  • AIDS Vaccines / administration & dosage
  • AIDS Vaccines / immunology*
  • Animals
  • Consensus Sequence
  • Cross Reactions
  • Fowlpox virus / immunology*
  • HIV Antibodies / blood
  • HIV Antigens / genetics
  • HIV Antigens / immunology
  • HIV Core Protein p24 / immunology
  • HIV Infections / prevention & control
  • Immunity, Cellular
  • Immunization, Secondary
  • Interferon-gamma / biosynthesis
  • Lymphocyte Count
  • Macaca nemestrina
  • Models, Animal
  • T-Lymphocytes / immunology*
  • Vaccines, DNA / administration & dosage
  • Vaccines, DNA / immunology*
  • Vaccines, Synthetic / genetics
  • Vaccines, Synthetic / immunology

Substances

  • AIDS Vaccines
  • HIV Antibodies
  • HIV Antigens
  • HIV Core Protein p24
  • Vaccines, DNA
  • Vaccines, Synthetic
  • Interferon-gamma