title: Vesicular stomatitis virus as a novel cancer vaccine vector to prime antitumor immunity amenable to rapid boosting with adenovirus.
abstract: Vesicular stomatitis virus (VSV) has proven to be an effective vaccine vector for immunization against viral infection, but its potential to induce an immune response to a self-tumor antigen has not been investigated. We constructed a recombinant VSV expressing human dopachrome tautomerase (hDCT) and evaluated its immunogenicity in a murine melanoma model. Intranasal delivery of VSV-hDCT activated both CD4(+) and CD8(+) DCT-specific T-cell responses. The magnitude of these responses could be significantly increased by booster immunization with recombinant adenovirus (Ad)-hDCT, which led to enhanced efficacy against B16-F10 melanoma in both prophylactic and therapeutic settings. Notably, the interval of VSV/Ad heterologous vaccination could be shortened to as few as 4 days, making it a potential regimen to rapidly expand antigen-specific effector cells. Furthermore, VSV-hDCT could increase DCT-specific T-cell responses primed by Ad-hDCT, suggesting VSV is efficient for both priming and boosting of the immune response against a self-tumor antigen.
authors: Centre for Gene Therapeutics, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.
authors: Byram W
authors: BW
authors: Bridle
authors: Jeanette E
authors: JE
authors: Boudreau
authors: Brian D
authors: BD
authors: Lichty
authors: Jérôme
authors: J
authors: Brunellière
authors: Kyle
authors: K
authors: Stephenson
authors: Sandeep
authors: S
authors: Koshy
authors: Jonathan L
authors: JL
authors: Bramson
authors: Yonghong
authors: Y
authors: Wan
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D005260:Female; D005822:Genetic Vectors / Q000235:genetics*; D006801:Humans; D007117:Immunization, Secondary; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000276:immunology*; D008175:Lung Neoplasms / Q000150:complications / Q000276:immunology / Q000628:therapy; D008545:Melanoma / Q000276:immunology* / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology; D018116:Vesiculovirus / Q000235:genetics*
chemical_list: D019496:Cancer Vaccines; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase