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Efficacy of RG1-VLP...
Efficacy of RG1-VLP Vaccination against Infections with Genital and Cutaneous Human Papillomaviruses
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Schellenbacher, Christina (author)
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Kwak, Kihyuck (author)
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Fink, Dieter (author)
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Shafti-Keramat, Saeed (author)
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Huber, Bettina (author)
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Jindra, Christoph (author)
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- Faust, Helena (author)
- Lund University,Lunds universitet,Klinisk mikrobiologi, Malmö,Forskargrupper vid Lunds universitet,Clinical Microbiology, Malmö,Lund University Research Groups
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- Dillner, Joakim (author)
- Karolinska Institutet
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Roden, Richard B. S. (author)
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Kirnbauer, Reinhard (author)
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(creator_code:org_t)
- Elsevier BV, 2013
- 2013
- English.
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In: Journal of Investigative Dermatology. - : Elsevier BV. - 1523-1747 .- 0022-202X. ; 133:12, s. 2706-2713
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Abstract
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Dermatologi och venereologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Dermatology and Venereal Diseases (hsv//eng)
Publication and Content Type
- art (subject category)
- ref (subject category)
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Schellenbacher, ...
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Kwak, Kihyuck
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Fink, Dieter
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Shafti-Keramat, ...
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Huber, Bettina
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Jindra, Christop ...
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show more...
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Faust, Helena
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Dillner, Joakim
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Roden, Richard B ...
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Kirnbauer, Reinh ...
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Dermatology and ...
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Journal of Inves ...
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Lund University
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Karolinska Institutet