title: Human papillomavirus type 16 E2- and L1-specific serological and T-cell responses in women with vulval intraepithelial neoplasia.
abstract: Human papillomavirus type 16 (HPV-16)-associated vulval intraepithelial neoplasia (VIN) is frequently a chronic, multifocal high-grade condition with an appreciable risk of progression to vulval cancer. The requirement to treat women with VIN has recently stimulated the use of immunotherapy with E6/E7 oncogene vaccines. Animal models have shown that E2 may also be a useful vaccine target for HPV-associated disease; however, little is known about E2 immunity in humans. This study investigated the prevalence of HPV-16 E2-specific serological and T-cell responses in 18 women with HPV-16-associated VIN and 17 healthy volunteers. E2 responses were determined by full-length E2-GST ELISA with ELISPOT and proliferation assays using E2 C-terminal protein. As positive controls, HPV-16 L1 responses were measured using virus-like particles (VLPs) and L1-GST ELISA with ELISPOT and proliferation using VLPs as antigen. The VIN patients all showed a strong serological response to L1 compared with the healthy volunteers by VLP (15/18 vs 1/17, P<0.001) and L1-GST ELISA (18/18 vs 1/17, P<0.001). In contrast, L1-specific cellular immune responses were detected in a significant proportion of controls but were more prevalent in the VIN patients by proliferation assay (9/17 vs 17/18, P<0.02) and interferon-gamma ELISPOT (9/17 vs 13/18, P=not significant). Similar and low numbers of patients and controls were seropositive for E2-specific Ig (2/18 vs 1/17). In spite of previous studies showing the immunogenicity of E2 in eliciting primary T-cell responses in vitro, there was a low prevalence of E2 responses in the VIN patients and controls (2/18 vs 0/17).
authors.affiliation: Academic Unit of Obstetrics & Gynaecology, St Mary's Hospital, Whitworth Park, Manchester M13 0JH, UK.|Immunology Group, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Wilmslow Road, Manchester M20 4BX, UK.
authors.forename: Emma J
authors.initials: EJ
authors.lastname: Davidson
authors.affiliation: Applied Tumorvirology, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Sehr
authors.affiliation: Academic Unit of Obstetrics & Gynaecology, St Mary's Hospital, Whitworth Park, Manchester M13 0JH, UK.|Immunology Group, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Wilmslow Road, Manchester M20 4BX, UK.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Faulkner
authors.affiliation: Department of Biochemistry, University of Bristol, Bristol, UK.
authors.forename: Joanna L
authors.initials: JL
authors.lastname: Parish
authors.affiliation: Department of Biochemistry, University of Bristol, Bristol, UK.
authors.forename: Kevin
authors.initials: K
authors.lastname: Gaston
authors.affiliation: Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Moore
authors.affiliation: Applied Tumorvirology, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Pawlita
authors.affiliation: Academic Unit of Obstetrics & Gynaecology, St Mary's Hospital, Whitworth Park, Manchester M13 0JH, UK.
authors.forename: Henry C
authors.initials: HC
authors.lastname: Kitchener
authors.affiliation: Immunology Group, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Wilmslow Road, Manchester M20 4BX, UK.
authors.forename: Peter L
authors.initials: PL
authors.lastname: Stern
mesh_terms: D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D036022:Capsid Proteins; D002278:Carcinoma in Situ / Q000276:immunology* / Q000821:virology; D004268:DNA-Binding Proteins; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation; D008875:Middle Aged; D009856:Oncogene Proteins, Viral / Q000276:immunology*; D027383:Papillomaviridae / Q000276:immunology*; D030361:Papillomavirus Infections / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014412:Tumor Virus Infections / Q000276:immunology; D014846:Vulvar Neoplasms / Q000276:immunology* / Q000821:virology
chemical_list: D000914:Antibodies, Viral; D036022:Capsid Proteins; D004268:DNA-Binding Proteins; C054855:E2 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; C063317:L1 protein, Human papillomavirus type 16