The viral proteins that are expressed in HPV-infected (pre)malignant cells are considered ideal targets for immunological intervention. Most vaccine approaches for therapeutic vaccination aim to induce of HPV16 E7- and/or E6-specific cellular immunogenicity. As clinical success has so far been limited, novel approaches are required. We present the pre-clinical proof of concept of a replication-deficient adenovirus type 26 and 35 based vaccine for the treatment of HPV16 and HPV18 induced lesions.
We developed HPV16- and HPV18-specific antigens consisting of a fusion protein of non-functional E2, E6 and E7. By combing these antigens the Adenovirus vector-based vaccine will be suitable for the treatment of both early and late stage lesions, as E2 is predominantly expressed in early stage lesions whereas E6 and E7 are expressed in late stage lesions. Induction of HPV16 and HPV18-specific T-cells were assessed in mice and non-human primates (NHP).immunized with the vaccine. Therapeutic vaccine efficacy was evaluated using the well characterized TC-1 mouse tumor model.
Robust and long-lasting T-cell immunogenicity was induced upon immunization of mice and NHP with adenoviral vectors encoding the designed antigens. The developed vaccine vectors showed higher therapeutic efficacy compared to a benchmark control vaccine consisting of HPV16 E7 derived synthetic long peptides in the TC-1 mouse model.
The favorable immunogenicity and efficacy profile of the adenovirus based vectors along with the established procedures to manufacture these vectors at a large scale makes this approach attractive for clinical evaluation.
Khan et al ( manuscript under preparation)