Efficacy of RG1-VLP Vaccination against Infections with Genital and Cutaneous Human Papillomaviruses
(2013) In Journal of Investigative Dermatology 133(12). p.2706-2713- Abstract
- 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... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4197928
- author
- Schellenbacher, Christina ; Kwak, Kihyuck ; Fink, Dieter ; Shafti-Keramat, Saeed ; Huber, Bettina ; Jindra, Christoph ; Faust, Helena LU ; Dillner, Joakim ; Roden, Richard B. S. and Kirnbauer, Reinhard
- organization
- publishing date
- 2013
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Investigative Dermatology
- volume
- 133
- issue
- 12
- pages
- 2706 - 2713
- publisher
- Elsevier
- external identifiers
-
- wos:000327015400011
- scopus:84887827859
- pmid:23752042
- ISSN
- 1523-1747
- DOI
- 10.1038/jid.2013.253
- language
- English
- LU publication?
- yes
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- 92f957ca-71cc-4c81-8317-049d931d98cc (old id 4197928)
- date added to LUP
- 2016-04-01 10:27:55
- date last changed
- 2022-02-10 02:22:58
@article{92f957ca-71cc-4c81-8317-049d931d98cc,
abstract = {{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.}},
author = {{Schellenbacher, Christina and Kwak, Kihyuck and Fink, Dieter and Shafti-Keramat, Saeed and Huber, Bettina and Jindra, Christoph and Faust, Helena and Dillner, Joakim and Roden, Richard B. S. and Kirnbauer, Reinhard}},
issn = {{1523-1747}},
language = {{eng}},
number = {{12}},
pages = {{2706--2713}},
publisher = {{Elsevier}},
series = {{Journal of Investigative Dermatology}},
title = {{Efficacy of RG1-VLP Vaccination against Infections with Genital and Cutaneous Human Papillomaviruses}},
url = {{http://dx.doi.org/10.1038/jid.2013.253}},
doi = {{10.1038/jid.2013.253}},
volume = {{133}},
year = {{2013}},
}