title: Cell-mediated immune responses to COPV early proteins.
abstract: Cell-mediated immunity plays a key role in the regression of papillomavirus-induced warts and intra-epithelial lesions but the target antigens that induce this response are not clear. Canine oral papillomavirus (COPV) infection of the oral cavity in dogs is a well-characterized model of mucosal papillomavirus infection that permits analysis of the immune events during the infectious cycle. In this study we show that during the COPV infectious cycle, systemic T cell responses to peptides of several early proteins particularly the E2 protein, as assayed by delayed type hypersensitivity, lymphoproliferation and IFN-gamma ELISPOT, can be detected. The maximal response occurs in a narrow time window that coincides with maximal viral DNA replication and wart regression: thereafter, systemic T cell responses to early proteins decline quite rapidly. Vaccination using particle-mediated immunotherapeutic delivery (PMID) of codon-modified COPV E2 and E1 genes induces strong antigen-specific cell-mediated immune responses in the vaccinated animals. These data show that therapeutic immunization by PMID with codon-modified E2 is completely effective, that to E1 is partially protective, that this correlates with the intensity of antigen-specific cell-mediated immune responses and, further, they emphasize the importance of these responses and the route of immunization in the generation of protective immunity.
authors.affiliation: Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
authors.forename: Suchitra
authors.initials: S
authors.lastname: Jain
authors.forename: Richard A
authors.initials: RA
authors.lastname: Moore
authors.forename: Davina M
authors.initials: DM
authors.lastname: Anderson
authors.forename: Gerald W
authors.initials: GW
authors.lastname: Gough
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Stanley
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004283:Dog Diseases / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D004285:Dogs; D005260:Female; D052691:Lambdapapillomavirus / Q000276:immunology* / Q000378:metabolism / Q000472:pathogenicity; D008297:Male; D009061:Mouth Mucosa / Q000276:immunology; D009062:Mouth Neoplasms / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D030361:Papillomavirus Infections / Q000276:immunology / Q000517:prevention & control / Q000662:veterinary*; D013601:T-Lymphocytes / Q000276:immunology*; D014611:Vaccination; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*; D014764:Viral Proteins / Q000276:immunology*; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D019444:Vaccines, DNA; D014764:Viral Proteins; D014765:Viral Vaccines