Interferon-beta expressed by a rabies virus-based HIV-1 vaccine vector serves as a molecular adjuvant and decreases pathogenicity

Virology. 2008 Dec 20;382(2):226-38. doi: 10.1016/j.virol.2008.09.019. Epub 2008 Oct 21.

Abstract

Type I interferon is important in anti-viral responses and in coordinating the innate immune response. Here we explore the use of interferon-beta to adjuvant the response to a rabies virus (RV) vaccine vector expressing both HIV-1 Gag and IFN-beta. Viral load and immune responses of immunized mice were analyzed over time. Our results indicate that the RV expressing IFN-beta (IFN+) is highly attenuated when compared to control RV and demonstrate that the expression of IFN-beta reduces viral replication approximately 100-fold. Despite the decrease in replication, those mice immunized with the IFN+ RV had a significantly greater number of activated CD8+ T cells. The increased activation of CD8+ T cells was dependent on IFN-beta signaling, as we saw no difference following infection of IFNAR-/- mice. Although mice immunized with IFN+ have a greater primary immune response than controls, immunized mice that were challenged with vaccinia-expressing Gag had no significant difference in the number or functionality of CD8+ T cells. The increased CD8+ T cell activation in the presence of IFN-beta, even with greatly reduced viral replication, indicates the beneficial effect of IFN-beta for the host.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • AIDS Vaccines / genetics*
  • AIDS Vaccines / immunology*
  • Adjuvants, Immunologic / genetics*
  • Animals
  • Antibodies, Viral / biosynthesis
  • Antigen-Presenting Cells / immunology
  • Base Sequence
  • CD8-Positive T-Lymphocytes / immunology
  • DNA Primers / genetics
  • Genes, gag
  • Genetic Vectors
  • HIV-1 / genetics*
  • HIV-1 / immunology*
  • HIV-1 / physiology
  • Immunity, Innate
  • Immunity, Mucosal
  • Immunoglobulin G / biosynthesis
  • Interferon Type I / genetics*
  • Interferon Type I / immunology*
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Rabies virus / genetics*
  • Rabies virus / immunology
  • Rabies virus / pathogenicity
  • Receptor, Interferon alpha-beta / deficiency
  • Receptor, Interferon alpha-beta / genetics
  • Recombinant Proteins
  • Recombination, Genetic
  • Signal Transduction
  • Virus Replication

Substances

  • AIDS Vaccines
  • Adjuvants, Immunologic
  • Antibodies, Viral
  • DNA Primers
  • Immunoglobulin G
  • Interferon Type I
  • Recombinant Proteins
  • Receptor, Interferon alpha-beta