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

2.50
Hdl Handle:
http://hdl.handle.net/10541/82354
Title:
Human papillomavirus type 16 E2- and L1-specific serological and T-cell responses in women with vulval intraepithelial neoplasia.
Authors:
Davidson, Emma J; Sehr, Peter; Faulkner, Rebecca L; Parish, Joanna L; Gaston, Kevin; Moore, Richard A; Pawlita, Michael; Kitchener, Henry C; Stern, Peter L
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).
Affiliation:
Immunology Group, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Wilmslow Road, Manchester M20 4BX, UK.
Citation:
Human papillomavirus type 16 E2- and L1-specific serological and T-cell responses in women with vulval intraepithelial neoplasia. 2003, 84 (Pt 8):2089-97 J. Gen. Virol.
Journal:
The Journal of General Virology
Issue Date:
Aug-2003
URI:
http://hdl.handle.net/10541/82354
DOI:
10.1099/vir.0.19095-0
PubMed ID:
12867639
Type:
Article
Language:
en
ISSN:
0022-1317
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorDavidson, Emma J-
dc.contributor.authorSehr, Peter-
dc.contributor.authorFaulkner, Rebecca L-
dc.contributor.authorParish, Joanna L-
dc.contributor.authorGaston, Kevin-
dc.contributor.authorMoore, Richard A-
dc.contributor.authorPawlita, Michael-
dc.contributor.authorKitchener, Henry C-
dc.contributor.authorStern, Peter L-
dc.date.accessioned2009-09-23T13:22:33Z-
dc.date.available2009-09-23T13:22:33Z-
dc.date.issued2003-08-
dc.identifier.citationHuman papillomavirus type 16 E2- and L1-specific serological and T-cell responses in women with vulval intraepithelial neoplasia. 2003, 84 (Pt 8):2089-97 J. Gen. Virol.en
dc.identifier.issn0022-1317-
dc.identifier.pmid12867639-
dc.identifier.doi10.1099/vir.0.19095-0-
dc.identifier.urihttp://hdl.handle.net/10541/82354-
dc.description.abstractHuman 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).en
dc.language.isoenen
dc.subjectVulvar Canceren
dc.subjectTumour Virus Infectionsen
dc.subject.meshAdult-
dc.subject.meshAntibodies, Viral-
dc.subject.meshCapsid Proteins-
dc.subject.meshCarcinoma in Situ-
dc.subject.meshDNA-Binding Proteins-
dc.subject.meshFemale-
dc.subject.meshHumans-
dc.subject.meshLymphocyte Activation-
dc.subject.meshMiddle Aged-
dc.subject.meshOncogene Proteins, Viral-
dc.subject.meshPapillomaviridae-
dc.subject.meshPapillomavirus Infections-
dc.subject.meshT-Lymphocytes-
dc.subject.meshTumor Virus Infections-
dc.subject.meshVulvar Neoplasms-
dc.titleHuman papillomavirus type 16 E2- and L1-specific serological and T-cell responses in women with vulval intraepithelial neoplasia.en
dc.typeArticleen
dc.contributor.departmentImmunology Group, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Wilmslow Road, Manchester M20 4BX, UK.en
dc.identifier.journalThe Journal of General Virologyen

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