title: The magnitude of the CD8+ T cell response produced by recombinant virus vectors is a function of both the antigen and the vector.
abstract: Virus-based recombinant vaccines have proven highly effective at generating protective CD8+ T cell responses. Multiple vector platforms are available, however, little is known about the relative influence of the different vectors on the transgene-specific CD8+ T cell population. To address this question, we compared several characteristics of the CD8+ T cell response elicited by recombinant adenovirus (rAd) and vaccinia virus (rVV). We found that following rAd immunization the transgene-specific CD8+ T cell response peaked around day 12 and was larger and more sustained than the response produced by rVV. In addition, the CD8+ T cell response generated by rAd was directed primarily against the transgene, whereas the CD8+ T cell response produced by rVV principally targeted the vector backbone. In addition, we also observed that transgene selection also impacted on the magnitude of the CD8+ T cell response elicited by both vectors. Despite differences in the magnitude of the anti-transgene CD8+ T cell response, both vectors elicited CD8+ T cell populations with similar cytokine production, functional avidity and cytolytic activity. In addition, plasmid priming prior to immunization with either rAd or rVV only impacted the magnitude of the transgene gene specific CD8+ T cell response. Our study demonstrates that both vector and transgene selection can influence the magnitude of the CD8+ T cell response, but they do not influence functionality.
authors.affiliation: Center for Gene Therapeutics, Department of Pathology and Molecular Medicine, McMaster University, Room MDCL-5025, 1200 Main Street West, Hamilton, Ont., Canada L8N 3Z5.
authors.forename: James
authors.initials: J
authors.lastname: Millar
authors.forename: Dilan
authors.initials: D
authors.lastname: Dissanayake
authors.forename: Teng Chih
authors.initials: TC
authors.lastname: Yang
authors.forename: Natalie
authors.initials: N
authors.lastname: Grinshtein
authors.forename: Carole
authors.initials: C
authors.lastname: Evelegh
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Wan
authors.forename: Jonathan
authors.initials: J
authors.lastname: Bramson
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D000941:Antigens / Q000235:genetics / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D005822:Genetic Vectors / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics*; D019076:Transgenes / Q000235:genetics; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology*; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology
chemical_list: D000941:Antigens; D011994:Recombinant Proteins; D014764:Viral Proteins