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

摘要: Certain cutaneous human papillomaviruses (HPVs), which are ubiquitous and acquired early during childhood, can cause a variety of skin tumors likely involved in the development non-melanoma cancer, especially immunosuppressed patients. Hence, burden these clinical manifestations demands for prophylactic approach. To evaluate whether protective efficacy vaccine is potentially translatable to patients, we used rodent Mastomys coucha that naturally infected with natalensis papillomavirus (MnPV). This type induces not only benign tumours, such as papillomas keratoacanthomas, but also squamous cell carcinomas, thereby allowing straightforward read-out successful vaccination small immunocompetent laboratory animal. Here, examined virus-like particle (VLP)-based on either previously or newly established infections. VLPs raise strong long-lasting neutralizing antibody response confers protection even under systemic long-term cyclosporine A treatment. Remarkably, completely prevents appearance well malignant tumors. Protection involves maintenance low viral load by an antibody-dependent prevention virus spread. Our results provide first evidence elicit effective immune conditions outbred animal model, irrespective infection status at time vaccination. These findings basis potent strategies against HPV infections HPV-induced tumors, patients awaiting organ transplantation.