title: Efficacy of RG1-VLP vaccination against infections with genital and cutaneous human papillomaviruses.
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.
authors.affiliation: Laboratory of Viral Oncology (LVO), Division of Immunology, Allergy and Infectious Diseases (DIAID), Department of Dermatology, Medical University Vienna (MUW), Vienna, Austria.
authors.forename: Christina
authors.initials: C
authors.lastname: Schellenbacher
authors.affiliation: Department of Pathology, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Kihyuck
authors.initials: K
authors.lastname: Kwak
authors.affiliation: Institute of Laboratory Animal Science, Veterinary University Vienna, Vienna, Austria.
authors.forename: Dieter
authors.initials: D
authors.lastname: Fink
authors.affiliation: Laboratory of Viral Oncology (LVO), Division of Immunology, Allergy and Infectious Diseases (DIAID), Department of Dermatology, Medical University Vienna (MUW), Vienna, Austria.
authors.forename: Saeed
authors.initials: S
authors.lastname: Shafti-Keramat
authors.affiliation: Laboratory of Viral Oncology (LVO), Division of Immunology, Allergy and Infectious Diseases (DIAID), Department of Dermatology, Medical University Vienna (MUW), Vienna, Austria.
authors.forename: Bettina
authors.initials: B
authors.lastname: Huber
authors.affiliation: Laboratory of Viral Oncology (LVO), Division of Immunology, Allergy and Infectious Diseases (DIAID), Department of Dermatology, Medical University Vienna (MUW), Vienna, Austria.
authors.forename: Christoph
authors.initials: C
authors.lastname: Jindra
authors.affiliation: Department of Laboratory Medicine, Lund University, Malmö University Hospital, Malmö, Sweden.
authors.forename: Helena
authors.initials: H
authors.lastname: Faust
authors.affiliation: Department of Laboratory Medicine, Medical Epidemiology and Biostatistics, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Joakim
authors.initials: J
authors.lastname: Dillner
authors.affiliation: Department of Pathology, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Richard B S
authors.initials: RBS
authors.lastname: Roden
authors.affiliation: 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.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Kirnbauer
mesh_terms: D000818:Animals; D036022:Capsid Proteins / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D005260:Female; D006801:Humans; D007156:Immunologic Memory; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D009856:Oncogene Proteins, Viral / Q000276:immunology*; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000276:immunology / Q000517:prevention & control*; D053918:Papillomavirus Vaccines / Q000276:immunology*; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012871:Skin Diseases / Q000517:prevention & control / Q000821:virology; D013601:T-Lymphocytes / Q000166:cytology; D002583:Uterine Cervical Neoplasms / Q000517:prevention & control; D014611:Vaccination / Q000379:methods; D058425:Vaccines, Virus-Like Particle / Q000276:immunology*
chemical_list: D036022:Capsid Proteins; D000939:Epitopes; C063316:L2 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D053918:Papillomavirus Vaccines; D058425:Vaccines, Virus-Like Particle