Recombinant fowlpox virus elicits transient cytotoxic T cell responses due to suboptimal innate recognition and recruitment of T cell help.
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.
Diener
Kerrilyn R
KR
Hanson Institute, Adelaide, S.A., 5000, Australia.
Lousberg
Erin L
EL
Beukema
Emma L
EL
Yu
Anastasia
A
Howley
Paul M
PM
Brown
Michael P
MP
Hayball
John D
JD
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D005587:Fowlpox virus / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology*
D014614:Vaccines, Synthetic; D014765:Viral Vaccines; D007371:Interferon-gamma; D010047:Ovalbumin