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J Invest Dermatol. 2013 Dec;133(12):2706-2713. doi: 10.1038/jid.2013.253. Epub 2013 May 10.

Efficacy of RG1-VLP vaccination against infections with genital and cutaneous human papillomaviruses.

Author information

1
Laboratory of Viral Oncology (LVO), Division of Immunology, Allergy and Infectious Diseases (DIAID), Department of Dermatology, Medical University Vienna (MUW), Vienna, Austria.
2
Department of Pathology, Johns Hopkins University, Baltimore, Maryland, USA.
3
Institute of Laboratory Animal Science, Veterinary University Vienna, Vienna, Austria.
4
Department of Laboratory Medicine, Lund University, Malmö University Hospital, Malmö, Sweden.
5
Department of Laboratory Medicine, Medical Epidemiology and Biostatistics, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
6
Laboratory of Viral Oncology (LVO), Division of Immunology, Allergy and Infectious Diseases (DIAID), Department of Dermatology, Medical University Vienna (MUW), Vienna, Austria. Electronic address: reinhard.kirnbauer@meduniwien.ac.at.

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.

PMID:
23752042
PMCID:
PMC3826974
DOI:
10.1038/jid.2013.253
[Indexed for MEDLINE]
Free PMC Article

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