title: Therapeutic immunisation with COPV early genes by epithelial DNA delivery.
abstract: Following challenge with COPV (canine oral papillomavirus), DNA plasmids encoding COPV L1, E1 or E2 protein were delivered into oral mucosal and cutaneous sites in beagles using particle-mediated immunotherapeutic delivery (PMID). Two weeks post-challenge, a priming dose of 8 microg DNA was delivered followed by a booster dose after a further two weeks. A group of control dogs were vaccinated using plasmid DNA encoding Hepatitis B virus surface (HBVs) gene. All of the control animals developed warts at the vast majority of sites (94%). All of the animals given wild type L1, E1, or E2 developed warts at most sites (88%, 75%, and 88%, respectively). The animals given codon optimised E2 however, were protected from wart growth with only one tiny lesion seen on a single animal that persisted for only a few days. The E1 codon optimised group was also significantly protected with a far lower number of smaller warts (48%) that persisted for a shorter duration. These data suggest that therapeutic immunisation by PMID with papillomavirus early genes is effective and emphasizes the importance of antigen load in the generation of protective responses to papillomavirus proteins.
authors.affiliation: Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK. ram36@cam.ac.uk
authors.forename: Richard A
authors.initials: RA
authors.lastname: Moore
authors.forename: Sarah
authors.initials: S
authors.lastname: Walcott
authors.forename: Kate L
authors.initials: KL
authors.lastname: White
authors.forename: Davina M
authors.initials: DM
authors.lastname: Anderson
authors.forename: Suchitra
authors.initials: S
authors.lastname: Jain
authors.forename: Andrew
authors.initials: A
authors.lastname: Lloyd
authors.forename: Peter
authors.initials: P
authors.lastname: Topley
authors.forename: Lindy
authors.initials: L
authors.lastname: Thomsen
authors.forename: Gerald W
authors.initials: GW
authors.lastname: Gough
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Stanley
mesh_terms: D000818:Animals; D036022:Capsid Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D004195:Disease Models, Animal; D004285:Dogs; D004848:Epithelium / Q000821:virology*; D006801:Humans; D007114:Immunization; D009061:Mouth Mucosa / Q000821:virology; D010212:Papilloma / Q000188:drug therapy* / Q000821:virology; D027383:Papillomaviridae / Q000235:genetics / Q000276:immunology*; D030361:Papillomavirus Infections / Q000188:drug therapy / Q000821:virology; D010957:Plasmids; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D014764:Viral Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*
chemical_list: D036022:Capsid Proteins; C097166:L1 protein, canine oral papillomavirus; D019444:Vaccines, DNA; D014764:Viral Proteins; D014765:Viral Vaccines