A human papillomavirus 8 E7 protein produced in plants is able to trigger the mouse immune system and delay the development of skin lesions

We investigated the potential of Nicotiana benthamiana to express the E7 protein of human papillomavirus 8 (HPV-8), a paradigm genotype among cutaneous HPVs. The protein, modified in its putative pRb-binding domain (E7(QGD)), was transiently expressed in leaves following infiltration with agrobacteria carrying either a binary vector combined with silencing suppressor constructs or replicating tobacco mosaic virus (TMV)-based vectors with different targeting signals. HPV-8 E7(QGD) yields ranged from 250 ng to 4.6 mg per gram of fresh leaf tissue. The highest yields were obtained with TMV-based vectors targeting the antigen to the apoplast. HPV8-CER (H2(q)) mice transformed with the complete early region of HPV-8 showed a delay in the onset of skin papillomatous lesions and produced E7-specific immunoglobulins G when inoculated subcutaneously with leaf extracts expressing E7(QGD). Furthermore, we demonstrated that the plant-made HPV-8 E7(QGD) induced a specific cytotoxic response in C57BL/6 (H2(b)) mice.