The rodent Mastomys coucha is naturally and persistently infected with Mastomys natalensis papilloma virus (MnPV). The animals are unique in spontaneously developing MnPV-induced benign skin lesions (papillomas, keratoacanthomas) that also can progress to non-melanoma skin cancer. Infection occurs early in lifetime, similarly to cutaneous HPV, and high viral loads can be detected in the skin in older animals, which trigger the onset of papilloma development. Therefore, M. coucha represents an excellent model to investigate prophylactic approaches against papillomavirus-caused skin tumors under natural conditions. The aim of this preclinical study is to investigate a virus-like particle (VLP)-based vaccine with respect to the prevention of skin tumors under conditions of primary or already established infection, both in immunocompetent and immunosuppressed animals.
A papillomavirus-free Mastomys colony was raised by hysterectomy of animals from the naturally infected colony. MnPV infected and non-infected Mastomys were immunized with MnPV VLPs and subsequently, depending on the group, experimentally infected and/or fed chronically an immunosuppressive diet. Elicitation of protective antibodies was evaluated by VLP-ELISA and a pseudovirion-based neutralization assay.
We found strong and steadily increased L1 antibody levels in immunized animals, while in naturally infected animals immune response against capsids is delayed and only reaches immunization-like levels in older animals. Animals fed with a Cyclosporin A diet did not show a different behaviour in their humoral immune response against either the virus or the vaccine. Our results show that the VLP-based vaccine effectively prevents the appearance of both skin lesions and tumors, irrespective of the infection status of the animal at the time of vaccination. Furthermore, vaccination results in an overall lower viral load in skin when compared to control animals. New data about this model will be presented.
Our findings provide evidence that VLP vaccination elicits an effective immune response even under immunosuppressive conditions and will support the clinical development of potent vaccination strategies against cutaneous HPV infections.