title: Developments in L2-based human papillomavirus (HPV) vaccines.
abstract: Infections with sexually transmitted high-risk Human Papillomavirus (hrHPV), of which there are at least 15 genotypes, are responsible for a tremendous disease burden by causing cervical, and subsets of other ano-genital and oro-pharyngeal carcinomas, together representing 5% of all cancer cases worldwide. HPV subunit vaccines consisting of virus-like particles (VLP) self-assembled from major capsid protein L1 plus adjuvant have been licensed. Prophylactic vaccinations with the 2-valent (HPV16/18), 4-valent (HPV6/11/16/18), or 9-valent (HPV6/11/16/18/31/33/45/52/58) vaccine induce high-titer neutralizing antibodies restricted to the vaccine types that cause up to 90% of cervical carcinomas, a subset of other ano-genital and oro-pharyngeal cancers and 90% of benign ano-genital warts (condylomata). The complexity of manufacturing multivalent L1-VLP vaccines limits the number of included VLP types and thus the vaccines' spectrum of protection, leaving a panel of oncogenic mucosal HPV unaddressed. In addition, current vaccines do not protect against cutaneous HPV types causing benign skin warts, or against beta-papillomavirus (betaPV) types implicated in the development of non-melanoma skin cancer (NMSC) in immunosuppressed patients. In contrast with L1-VLP, the minor capsid protein L2 contains type-common epitopes that induce low-titer yet broadly cross-neutralizing antibodies to heterologous PV types and provide cross-protection in animal challenge models. Efforts to increase the low immunogenicity of L2 (poly)-peptides and thereby to develop broader-spectrum HPV vaccines are the focus of this review.
authors.affiliation: Laboratory of Viral Oncology (LVO), Division of Immunology, Allergy and Infectious Diseases (DIAID), Department of Dermatology, Medical University of Vienna, Austria.
authors.forename: Christina
authors.initials: C
authors.lastname: Schellenbacher
authors.affiliation: Department of Pathology, Johns Hopkins University, Baltimore, MD, 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 of Vienna, Austria. Electronic address: reinhard.kirnbauer@meduniwien.ac.at.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Kirnbauer
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000096:biosynthesis; D000914:Antibodies, Viral / Q000096:biosynthesis*; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000096:biosynthesis / Q000276:immunology; D036022:Capsid Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D056738:Cross Protection; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D005260:Female; D006258:Head and Neck Neoplasms / Q000276:immunology / Q000473:pathology / Q000517:prevention & control* / Q000821:virology; D006801:Humans; D056724:Immunity, Humoral / Q000187:drug effects; D000071497:Immunogenicity, Vaccine; D051379:Mice; D009856:Oncogene Proteins, Viral / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D027383:Papillomaviridae / Q000187:drug effects / Q000254:growth & development / Q000276:immunology / Q000472:pathogenicity; D030361:Papillomavirus Infections / Q000276:immunology / Q000473:pathology / Q000517:prevention & control* / Q000821:virology; D053918:Papillomavirus Vaccines / Q000008:administration & dosage / Q000096:biosynthesis / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D002583:Uterine Cervical Neoplasms / Q000276:immunology / Q000473:pathology / Q000517:prevention & control* / Q000821:virology; D014611:Vaccination; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000096:biosynthesis / Q000276:immunology; D058425:Vaccines, Virus-Like Particle
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D019496:Cancer Vaccines; D036022:Capsid Proteins; D000939:Epitopes; C063316:L2 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D053918:Papillomavirus Vaccines; D011993:Recombinant Fusion Proteins; D022223:Vaccines, Subunit; D058425:Vaccines, Virus-Like Particle
keywords: Cervical cancer (CxCa); Cutaneous and anogenital warts (condylomata); HPV infection and disease; Human papillomavirus (HPV) vaccine; Minor capsid protein (L2); Squamous cell cancer (SCC)