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    Immune responses to oncogenic HPVs

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    Principal investigator:

    Contact isabelle.bourgault@inserm.fr - tel : +33 1 40 51 65 41

     

    Objective

    HPV-6, -11, -16 and -18 are the most prevalent HPV in genital condylomatous and neoplastic lesions of the vulva and the anal canal. The specific T-cell mediated immune responses to HPV play an essential role in controlling the development of these lesions. These responses are primarily directed against the early HIV proteins: E6 and E7. However, E2 protein is also a major specific target, in particular at the beginning of infection, when the viral genome is in its episomal form.

     

    The group

    In 2015, this group is composed of an engineer (INSERM), Suzanne Figueiredo-Morgado

     

    Research interests

    In patients with vulvar neoplasia, anti-HPV cellular immunity has been tested in circulating lymphocytes. We observed that the strong anti-HPV16 response was largely directed against the E2 peptide both in women with classical VIN and in their partner. The presence of both proliferative response and IFNg synthesis by CD4 + T-cells has been shown in women having no lesion following chemical therapy or surgury and their male partners who themselves had no clinical sign of infection. We concluded, in the absence of E2 in the infectious viral particles, that men had been infected with HPV16 and had controlled the virus. Women with chronic and persistent lesions had no anti-E2 CD4 + T-cell response, making the presence of anti-E2 specific T-cell responses, a marker of infection/disease control. We now analyze the local development of immune responses and the cytokine profile of anal lesions caused by oncogenic HPV in order to better understand the role of the immune response in such lesions.

     

    Main publications

    S. Jacobelli, F. Sanaa, M. Moyal Barracco, M. Pelisse, S. Berville, P. Villefroy, M.O. North, S. Figueiredo, B. Charmeteau, T. Clerici, F. Plantier, N. Dupin, M.F. Avril, J.G. Guillet, R Cheynier, I. Bourgault Villada. (2011) Anti-HPV16 E2 peptides blood T-cell responses in healthy male partners of women affected with usual vulvar intraepithelial neoplasia. PloS One, 7(5): e37042.

    I. Bourgault Villada. (2010) Vaccination against HPV-16 for vulvar intraepithelial neoplasia. N. Engl. J. Med., 362: 655-6.

    I. Bourgault Villada, M. Moyal Barracco, S. Berville, M.L. Bafounta, C. Longvert, V. Prémel, P.Villefroy, E. Jullian, T. Clerici, B. Paniel, B. Maillère, J. Choppin, J.G. Guillet. (2010) HPV-16-specific T-cell responses in classic HPV-related vulvar intraepithelial neoplasia. Determination of strongly immunogenic regions from E6 and E7 proteins. Clin. Exp. Immunol., 159: 45-56

    Bourgault-Villada, I., Moyal-Barracco, M., Ziol, M., Chaboissier, A., Barget, N., Berville, S., Paniel, B., Jullian, E., Clerici, T., Maillere, B., Guillet, J. G. (2004) Spontaneous regression of grade 3 vulvar intraepithelial neoplasia associated with HPV 16 specific CD4+ and CD8+ T cell responses. Cancer Res. 64:8761-66

    I. Bourgault Villada, N. Bénéton, C. Bony, F. Connan, J. Monsonégo, A. Bianchi, P. Saiag, J.P. Lévy, J.G. Guillet, J. Choppin. (2000) Identification in humans of HPV-16 E6 and E7 protein epitopes recognized by cytolytic T lymphocytes in association with HLA-B18 and determination of the HLA-B18 specific binding motif. Eur. J. Immunol., 30: 2281-2289.

     

    Patents

    French Patent n° 97.15246. Micelles mixtes de lipopeptides pour l’induction d’une réponse immunitaire et leurs utilisations à des fins thérapeutiques. Gras-Masse H, Guillet J.G, Bourgault-Villada I, Bossus M, Lippens G, Wieruszeski, J, Tartar A. License developed by PIL/Biovector.

    International patent WO 02/090382 A2. Mélange de peptides issus des protéines E6 et/ou E7 de papillomavirus et leurs applications. Maillère B, Bourgault Villada I, Pouvelle Morratille S, Guillet J.G. license development (2004-2006) by ISA-PHARMA.

    International patent WO 00/75336 A2. Fragments protéiques polyépitopiques des protéines E6 et E7 de HPV, leur obtention et leurs utilisations, notamment en vaccination. Choppin J, Bourgault Villada I, Guillet J.G, Connan F, Ferries E. Licensed to ISA-PHARMA

    French patent n° FR 0203189. Utilisation de mélange de lipopeptides pour la fabrication de vaccins Guillet J.G, Bourgault Villada I, Dupuis M, Gras Masse H, Bourel L, Melnyk O, Joly P, Bonnet D, Malingue F, Grand Jean C, Georges B.

     

    Financial supports

    This program is supported by la société Française de dermatologie

     

     

     

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