Induction of a strong HIV-specific CD8+ T cell response in mice using a fowlpox virus vector expressing an HIV-1 multi-CTL-epitope polypeptide

Viral Immunol. 2002;15(2):337-56. doi: 10.1089/08828240260066260.

Abstract

Recombinant avipoxvirus vectors are attractive candidates for use in vaccination strategies for infections such as human immunodeficiency virus type 1 (HIV-1), where induction of a CD8+ T cell response is thought to be an important component of protective immunity. Here, we report the expression of a multiepitope polypeptide (TAB9) composed of the central 15 amino acids of the V3 loop from six different isolates of HIV-1 in a fowlpox virus (FWPV) vector, and the use of this vector (FPTAB9LZ) to induce strong HIV-specific CD8+ T cell responses in mice. In animals immunized twice intravenously with FPTAB9LZ, almost 2% of the CD8+ T cells in the spleen were shown to produce IFN-gamma in response to stimulation with HIV-1 peptides 1 week after the second immunization. The most dominant response was to the HIV-1 IIIB peptide. A strong HIV-specific response was also induced by intraperitoneal immunization of mice with FPTAB9LZ, whilst subcutaneous immunization elicited a weaker response. Intraperitoneal immunization with FPTAB9LZ was also shown to provide protection against challenge with a recombinant vaccinia virus expressing antigens, including those in TAB9. These results confirm the potential of FWPV vectors for use in HIV vaccination strategies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Line
  • Drug Administration Routes
  • Epitopes / genetics
  • Epitopes / immunology*
  • Epitopes, T-Lymphocyte / genetics
  • Epitopes, T-Lymphocyte / immunology*
  • Fowlpox virus / genetics
  • Fowlpox virus / immunology*
  • Gene Expression
  • Genetic Vectors / genetics
  • Genetic Vectors / immunology*
  • HIV Antigens / genetics
  • HIV Antigens / immunology*
  • HIV Envelope Protein gp120 / genetics
  • HIV Envelope Protein gp120 / immunology*
  • HIV-1 / genetics
  • HIV-1 / immunology*
  • Humans
  • Injections, Intravenous
  • Mice
  • Peptide Fragments / genetics
  • Peptide Fragments / immunology*
  • Peptides / genetics
  • Peptides / immunology*
  • Recombination, Genetic
  • Spleen / cytology
  • T-Lymphocytes, Cytotoxic / immunology
  • Vaccination
  • Vaccinia virus

Substances

  • Epitopes
  • Epitopes, T-Lymphocyte
  • HIV Antigens
  • HIV Envelope Protein gp120
  • HIV envelope protein gp120 (305-321)
  • Peptide Fragments
  • Peptides
  • TAB9