title: Immunogenicity in mice and rhesus monkeys vaccinated with recombinant vaccinia virus expressing bivalent E7E6 fusion proteins from human papillomavirus types 16 and 18.
abstract: BACKGROUND
  Persistent infection with high-risk human papillomavirus (HPV) is a predominant cause of cervical cancer, and HPV16 and HPV18 occur in 50% and 20% of cervical cancer cases, respectively. The viral oncogenes E6 and E7 are constitutively expressed by HPV-associated tumour cells and can therefore be used as target antigens for immunotherapy. In this study, we constructed a recombinant vaccinia virus co-expressing the HPV16/18 E7E6 fusion proteins (rVVJ16/18E7E6) for use as a therapeutic vaccine for the treatment of HPV16⁺ and HPV18⁺ cancers.
  
  
  METHODS
  We constructed a bivalent recombinant vaccinia virus expressing modified E7E6 fusion proteins of HPV type 16 and 18 (rVVJ16/18E7E6) based on the vaccinia virus Tiantan strain. We then defined the cellular immune responses to the virus in mice and rhesus monkeys and assessed antitumour efficacy of these responses in mice using the TC-1 tumour challenge model.
  
  
  RESULTS
  Our data demonstrated that rVVJ16/18E7E6 was able to elicit varying levels of CD8⁺ T cell immune responses and lysis of target cells in mice in response to peptides HPV16E7₄₉₋₅₇ and HPV18E6₆₇₋₇₅. Furthermore, the virus was also able to induce anti-tumour responses in the HPV16⁺ TC-1 tumour challenge model, including partial protection (30-40%) and delayed tumour appearance. In addition, the virus was able to induce immune responses in rhesus monkeys.
  
  
  CONCLUSIONS
  The recombinant vaccinia virus rVVJ16/18E7E6 can generate clear and significant cellular immunity in both mice and rhesus monkeys. These data provide a basis for the use of this recombinant virus as a potential vaccine candidate for further study.
authors.affiliation: State Key Laboratory for Molecular Virology and Genetic Engineering, Biotech Center for Viral Disease Emergency, National Institute for Viral Disease Control and Prevention, China CDC, Changpingqu, Beijing 102206, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhao
authors.forename: Binlei
authors.initials: B
authors.lastname: Liu
authors.forename: Jiao
authors.initials: J
authors.lastname: Ren
authors.forename: Jing
authors.initials: J
authors.lastname: Feng
authors.forename: Zheng
authors.initials: Z
authors.lastname: Pang
authors.forename: Jian
authors.initials: J
authors.lastname: Gao
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.forename: Wenjie
authors.initials: W
authors.lastname: Tan
authors.forename: Houwen
authors.initials: H
authors.lastname: Tian
authors.forename: Li
authors.initials: L
authors.lastname: Ruan
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002277:Carcinoma / Q000517:prevention & control; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D004337:Drug Carriers; D005260:Female; D005822:Genetic Vectors; D008253:Macaca mulatta; D051379:Mice; D008810:Mice, Inbred C57BL; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000276:immunology*; D050725:Papillomavirus E7 Proteins / Q000235:genetics / Q000276:immunology*; D053918:Papillomavirus Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D012097:Repressor Proteins / Q000235:genetics / Q000276:immunology*; D012376:Rodent Diseases / Q000517:prevention & control; D016896:Treatment Outcome; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D004337:Drug Carriers; C068651:E6 protein, Human papillomavirus type 16; C052603:E6 protein, Human papillomavirus type 18; C052633:E7 protein, Human papillomavirus type 18; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D053918:Papillomavirus Vaccines; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D014614:Vaccines, Synthetic; C059731:oncogene protein E7, Human papillomavirus type 16