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Efficacy of RG1-VLP Vaccination against Infections with Genital and Cutaneous Human Papillomaviruses
Licensed human papillomavirus (HPV) vaccines, based on virus-like particles (VLPs) self-assembled from major capsid protein L1, afford type-restricted protection against HPV types 16/18/6/11 (or 16/18 for the bivalent vaccine), which cause 70% of cervical cancers (CxCas) and 90% of genital warts. Ho...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3826974/ https://www.ncbi.nlm.nih.gov/pubmed/23752042 http://dx.doi.org/10.1038/jid.2013.253 |
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author | Schellenbacher, Christina Kwak, Kihyuck Fink, Dieter Shafti-Keramat, Saeed Huber, Bettina Jindra, Christoph Faust, Helena Dillner, Joakim Roden, Richard B.S. Kirnbauer, Reinhard |
author_facet | Schellenbacher, Christina Kwak, Kihyuck Fink, Dieter Shafti-Keramat, Saeed Huber, Bettina Jindra, Christoph Faust, Helena Dillner, Joakim Roden, Richard B.S. Kirnbauer, Reinhard |
author_sort | Schellenbacher, Christina |
collection | PubMed |
description | Licensed human papillomavirus (HPV) vaccines, based on virus-like particles (VLPs) self-assembled from major capsid protein L1, afford type-restricted protection against HPV types 16/18/6/11 (or 16/18 for the bivalent vaccine), which cause 70% of cervical cancers (CxCas) and 90% of genital warts. However, they do not protect against less prevalent high-risk (HR) types causing 30% of CxCa, or cutaneous HPV. In contrast, vaccination with the minor capsid protein L2 induces low-level immunity to type-common epitopes. Chimeric RG1-VLP presenting HPV16 L2 amino acids 17–36 (RG1 epitope) within the DE-surface loop of HPV16 L1 induced cross-neutralizing antisera. We hypothesized that RG1-VLP vaccination protects against a large spectrum of mucosal and cutaneous HPV infections in vivo. Immunization with RG1-VLP adjuvanted with human-applicable alum-MPL (aluminum hydroxide plus 3-O-desacyl-4′-monophosphoryl lipid A) induced robust L2 antibodies (ELISA titers 2,500–12,500), which (cross-)neutralized mucosal HR HPV16/18/45/37/33/52/58/35/39/51/59/68/73/26/69/34/70, low-risk HPV6/11/32/40, and cutaneous HPV2/27/3/76 (titers 25–1,000) using native virion- or pseudovirion (PsV)-based assays, and a vigorous cytotoxic T lymphocyte response by enzyme-linked immunospot. In vivo, mice were efficiently protected against experimental vaginal challenge with mucosal HR PsV types HPV16/18/45/31/33/52/58/35/39/51/59/68/56/73/26/53/66/34 and low-risk HPV6/43/44. Enduring protection was demonstrated 1 year after vaccination. RG1-VLP is a promising next-generation vaccine with broad efficacy against all relevant mucosal and also cutaneous HPV types. |
format | Online Article Text |
id | pubmed-3826974 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-38269742013-12-01 Efficacy of RG1-VLP Vaccination against Infections with Genital and Cutaneous Human Papillomaviruses Schellenbacher, Christina Kwak, Kihyuck Fink, Dieter Shafti-Keramat, Saeed Huber, Bettina Jindra, Christoph Faust, Helena Dillner, Joakim Roden, Richard B.S. Kirnbauer, Reinhard J Invest Dermatol Original Article Licensed human papillomavirus (HPV) vaccines, based on virus-like particles (VLPs) self-assembled from major capsid protein L1, afford type-restricted protection against HPV types 16/18/6/11 (or 16/18 for the bivalent vaccine), which cause 70% of cervical cancers (CxCas) and 90% of genital warts. However, they do not protect against less prevalent high-risk (HR) types causing 30% of CxCa, or cutaneous HPV. In contrast, vaccination with the minor capsid protein L2 induces low-level immunity to type-common epitopes. Chimeric RG1-VLP presenting HPV16 L2 amino acids 17–36 (RG1 epitope) within the DE-surface loop of HPV16 L1 induced cross-neutralizing antisera. We hypothesized that RG1-VLP vaccination protects against a large spectrum of mucosal and cutaneous HPV infections in vivo. Immunization with RG1-VLP adjuvanted with human-applicable alum-MPL (aluminum hydroxide plus 3-O-desacyl-4′-monophosphoryl lipid A) induced robust L2 antibodies (ELISA titers 2,500–12,500), which (cross-)neutralized mucosal HR HPV16/18/45/37/33/52/58/35/39/51/59/68/73/26/69/34/70, low-risk HPV6/11/32/40, and cutaneous HPV2/27/3/76 (titers 25–1,000) using native virion- or pseudovirion (PsV)-based assays, and a vigorous cytotoxic T lymphocyte response by enzyme-linked immunospot. In vivo, mice were efficiently protected against experimental vaginal challenge with mucosal HR PsV types HPV16/18/45/31/33/52/58/35/39/51/59/68/56/73/26/53/66/34 and low-risk HPV6/43/44. Enduring protection was demonstrated 1 year after vaccination. RG1-VLP is a promising next-generation vaccine with broad efficacy against all relevant mucosal and also cutaneous HPV types. Nature Publishing Group 2013-12 2013-06-27 /pmc/articles/PMC3826974/ /pubmed/23752042 http://dx.doi.org/10.1038/jid.2013.253 Text en Copyright © 2013 The Society for Investigative Dermatology, Inc http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/ |
spellingShingle | Original Article Schellenbacher, Christina Kwak, Kihyuck Fink, Dieter Shafti-Keramat, Saeed Huber, Bettina Jindra, Christoph Faust, Helena Dillner, Joakim Roden, Richard B.S. Kirnbauer, Reinhard Efficacy of RG1-VLP Vaccination against Infections with Genital and Cutaneous Human Papillomaviruses |
title | Efficacy of RG1-VLP Vaccination against Infections with Genital and Cutaneous Human Papillomaviruses |
title_full | Efficacy of RG1-VLP Vaccination against Infections with Genital and Cutaneous Human Papillomaviruses |
title_fullStr | Efficacy of RG1-VLP Vaccination against Infections with Genital and Cutaneous Human Papillomaviruses |
title_full_unstemmed | Efficacy of RG1-VLP Vaccination against Infections with Genital and Cutaneous Human Papillomaviruses |
title_short | Efficacy of RG1-VLP Vaccination against Infections with Genital and Cutaneous Human Papillomaviruses |
title_sort | efficacy of rg1-vlp vaccination against infections with genital and cutaneous human papillomaviruses |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3826974/ https://www.ncbi.nlm.nih.gov/pubmed/23752042 http://dx.doi.org/10.1038/jid.2013.253 |
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