The E7 oncoprotein from Human Papilloma Virus (HPV) is an attractive candidate for anti-cancer vaccine development. In this study, we engineered HPV16 E7 coding sequence (wild type or mutagenized sequence, E7GGG) as fusions to beta-1,3-1,4-glucanase (LicKM) of Clostridium thermocellum and produced in Nicotiana benthamiana plants using a transient expression system. Target antigens were purified and evaluated in mice for their potential as prophylactic and therapeutic vaccine candidates. Both fusion proteins induced E7-specific IgG and cytotoxic T-cell responses and protected mice against challenge with E7-expressing tumor cells. Furthermore, when administered after challenge, these plant-produced antigens prevented tumor development.