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J Gen Virol 84 (2003), 2089-2097; DOI 10.1099/vir.0.19095-0

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© 2003 Society for General Microbiology

Human papillomavirus type 16 E2- and L1-specific serological and T-cell responses in women with vulval intraepithelial neoplasia

Emma J. Davidson1,2, Peter Sehr3, Rebecca L. Faulkner1,2, Joanna L. Parish4, Kevin Gaston4, Richard A. Moore5, Michael Pawlita3, Henry C. Kitchener2 and Peter L. Stern1

1 Immunology Group, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Wilmslow Road, Manchester M20 4BX, UK
2 Academic Unit of Obstetrics & Gynaecology, St Mary's Hospital, Whitworth Park, Manchester M13 0JH, UK
3 Applied Tumorvirology, Deutsches Krebsforschungszentrum, Heidelberg, Germany
4 Department of Biochemistry, University of Bristol, Bristol, UK
5 Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK

Correspondence
Peter Stern
pstern{at}picr.man.ac.uk

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).




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