Recombinant fowlpox virus elicits transient cytotoxic T cell responses due to suboptimal innate recognition and recruitment of T cell help

Vaccine. 2008 Jul 4;26(29-30):3566-73. doi: 10.1016/j.vaccine.2008.05.015. Epub 2008 May 27.

Abstract

Recombinant fowlpox viruses (FPVs) have been used in a variety of vaccine strategies; however strong data clearly demonstrating the characteristics of the strength and nature of the resultant immune response elicited by these vectors are lacking. By utilising a recombinant variant of FPV which expresses the nominal antigen chicken ovalbumin (OVA), and assessing innate FPV- and OVA-specific adaptive immune responses, we show that recombinant FPV induces a rapid type I interferon (IFN) response, mediated primarily by plasmacytoid dendritic cells (pDCs). These cells are necessary for the development of a strong but transient CD8(+) T cell effector response directed against OVA-expressing target cells. We propose that a combination of suboptimal type I IFN production, poor CD4(+) T cell helper function and inefficient DC licensing likely contribute to this transient response. These findings now provide a sound basis for rational modifications to be made to recombinant FPV, designed to improve subsequent vaccine responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology
  • Dendritic Cells / immunology
  • Fowlpox virus / immunology*
  • Interferon-gamma / biosynthesis
  • Mice
  • Mice, Inbred C57BL
  • Ovalbumin / immunology
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Helper-Inducer / immunology*
  • Vaccines, Synthetic / immunology
  • Viral Vaccines / immunology*

Substances

  • Vaccines, Synthetic
  • Viral Vaccines
  • Interferon-gamma
  • Ovalbumin