title: Protective vaccination against papillomavirus-induced skin tumors under immunocompetent and immunosuppressive conditions: a preclinical study using a natural outbred animal model.
abstract: Certain cutaneous human papillomaviruses (HPVs), which are ubiquitous and acquired early during childhood, can cause a variety of skin tumors and are likely involved in the development of non-melanoma skin cancer, especially in immunosuppressed patients. Hence, the burden of these clinical manifestations demands for a prophylactic approach. To evaluate whether protective efficacy of a vaccine is potentially translatable to patients, we used the rodent Mastomys coucha that is naturally infected with Mastomys natalensis papillomavirus (MnPV). This skin type papillomavirus induces not only benign skin tumours, such as papillomas and keratoacanthomas, but also squamous cell carcinomas, thereby allowing a straightforward read-out for successful vaccination in a small immunocompetent laboratory animal. Here, we examined the efficacy of a virus-like particle (VLP)-based vaccine on either previously or newly established infections. VLPs raise a strong and long-lasting neutralizing antibody response that confers protection even under systemic long-term cyclosporine A treatment. Remarkably, the vaccine completely prevents the appearance of benign as well as malignant skin tumors. Protection involves the maintenance of a low viral load in the skin by an antibody-dependent prevention of virus spread. Our results provide first evidence that VLPs elicit an effective immune response in the skin under immunocompetent and immunosuppressed conditions in an outbred animal model, irrespective of the infection status at the time of vaccination. These findings provide the basis for the clinical development of potent vaccination strategies against cutaneous HPV infections and HPV-induced tumors, especially in patients awaiting organ transplantation.
authors.affiliation: Division of Viral Transformation Mechanisms, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Sabrina E
authors.initials: SE
authors.lastname: Vinzón
authors.affiliation: Division of Viral Transformation Mechanisms, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Ilona
authors.initials: I
authors.lastname: Braspenning-Wesch
authors.affiliation: Research Group Tumorvirus-specific Vaccination, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Müller
authors.affiliation: Department of Surgery, Experimental Surgery Division, University of Regensburg, Regensburg, Germany.
authors.forename: Edward K
authors.initials: EK
authors.lastname: Geissler
authors.affiliation: Department of Dermatology, Venereology and Allergy, Skin Cancer Center Charité, University Hospital of Berlin, Berlin, Germany.
authors.forename: Ingo
authors.initials: I
authors.lastname: Nindl
authors.affiliation: Department of Cellular and Molecular Pathology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Hermann-Josef
authors.initials: HJ
authors.lastname: Gröne
authors.affiliation: Division of Viral Transformation Mechanisms, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Kai
authors.initials: K
authors.lastname: Schäfer
authors.affiliation: Division of Viral Transformation Mechanisms, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Rösl
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D016867:Immunocompromised Host; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051189:Murinae; D030361:Papillomavirus Infections / Q000276:immunology / Q000517:prevention & control*; D053918:Papillomavirus Vaccines / Q000494:pharmacology*; D012878:Skin Neoplasms / Q000276:immunology / Q000517:prevention & control* / Q000821:virology*; D058425:Vaccines, Virus-Like Particle / Q000494:pharmacology*; D019562:Viral Load
chemical_list: D053918:Papillomavirus Vaccines; D058425:Vaccines, Virus-Like Particle