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.
Highlights
Papillomaviruses (PVs) infect mucosal and cutaneous squamous epithelia, where they can cause hyperproliferative lesions
Mimicking the situation of immunosuppressed organ transplant recipients (OTR) who acquire cutaneous human papillomaviruses (HPVs) infections already in childhood, we explored the efficacy of a vaccine in infected animals that underwent immunosuppression
We demonstrate for the first time the success of a vaccine against a skin papillomavirus in a natural outbred animal system, which completely prevents both benign and malignant skin tumor formation even under immunosuppressed conditions
Summary
Papillomaviruses (PVs) infect mucosal and cutaneous squamous epithelia, where they can cause hyperproliferative lesions. The association between HPV infection and skin cancer is still a matter of debate [2], there is increasing evidence that supports their role as a cofactor with UV radiation in the development of non-melanoma skin cancer (NMSC) [3]. OTR suffer from benign and premalignant skin lesions, such as actinic keratosis, keratoacanthomas and cutaneous warts, which are indisputably caused by cutaneous HPVs [10,11]. Such lesions appear over a large area of the skin, persist for years and significantly reduce life quality.
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