Protective Vaccination against Papillomavirus-Induced Skin Tumors under Immunocompetent and Immunosuppressive Conditions: A Preclinical Study Using a Natural Outbred Animal Model

PLoS Pathogens

Hermann-Josef Gröne¹  Ingo Nindl²  Edward K. Geissler³  Sabrina E. Vinzón⁴  Ilona Braspenning-Wesch⁴  Kai Schäfer⁴  Frank Rösl⁴  Martin Müller⁵ 

[1] Department of Cellular and Molecular Pathology, German Cancer Research Center (DKFZ), Heidelberg, Germany;Department of Dermatology, Venereology and Allergy, Skin Cancer Center Charité, University Hospital of Berlin, Berlin, Germany;Department of Surgery, Experimental Surgery Division, University of Regensburg, Regensburg, Germany;Division of Viral Transformation Mechanisms, German Cancer Research Center (DKFZ), Heidelberg, Germany;Research Group Tumorvirus-specific Vaccination, German Cancer Research Center (DKFZ), Heidelberg, Germany

关键词: Antibodies;    Vaccination;    immunization;    Skin tumors;    Human papillomavirus infection;    Skin infections;    Vaccines;    Animal sociality;    Immune suppression;   

DOI  :  10.1371/journal.ppat.1003924

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY