Novel viral vector platform for individualized vaccines
Dr. Ralf Amann
University of Tübingen - Interfaculty Institute for Cell Biology - Department of Immunology
Beneficiary: University of Tübingen
Funding exploratory phase: 01.06.2012 - 30.04.2014; 48,926 Euro
Funding feasibility phase: 01.08.2014 – 31.12.2016; 498,636 Euro
Although the development of cancer vaccines has been underway for decades, there is currently no approved, therapeutically effective vaccine. This is mainly due to the use of vaccine technologies that cannot induce an adequate T cell response. The desirable aim is to establish a safe vector platform with high flexibility and variability for rapid integration and expression of several foreign genes and strong T cell response without additional adjuvants. The Orf virus (ORFV) vector platform developed by us meets all these requirements and should therefore be tested in a clinically relevant model. To this end the Cottontail Rabbit Papillomavirus Model (CRPV) was chosen. In analogy to human disease, papillomavirus infections in rabbits lead to tumor development, with oncogenes E6 and E7 serving as targets for immunotherapy. Another advantage of the system is that rabbits differ genetically from inbred mice and therefore reflect the situation in humans.
During the feasibility phase we developed recombinant ORFV, which contained antigens from the papillomavirus. After tumor development, the animals were therapeutically immunized and tumor growth was observed. We were able to show that the tumors are well controlled after immunization and develop much more slowly. At the end of the experiment, the tumors in the immunized animals were on average three times smaller than in the non-immunized control animals. The response rate was 83% and also complete healing was observed. Furthermore, the therapeutic immunization was very well tolerated and showed no side effects.
The ORFV platform technology is currently being further developed in collaborations with pharmaceutical companies. In addition to therapeutic vaccines for the treatment of cancer, it also addresses individualized approaches, classical vaccines against infectious agents as well as animal health vaccines.