Teaching the immune system to destroy cancer or virus-infected cells through vaccination has been pursued as an appealing therapeutic strategy since decades. Although promising in vitro and in vivo data exists, the clinical success of such approaches lags behind what had been expected
Effective vaccines against intracellular pathogens or cancer should induce strong and durable T cell responses. We develop vaccination strategies that use combinations of distinct adjuvants that improve immune responses synergistically. This process is amongst others associated with the induction of different chemokines and chemokine receptors that orchestrate cell localization and migration.
1. Combining different adjuvants to improve vaccines against viral infections
Whenever an infection ocurs in humans or animals, innate effector cells like macrophages or NK are the first immune cells to combat the microbes, followed by cytotoxic CD8+ T Cells (CTL) after some days. These CTL specifically destroy virally infected cells. After several weeks, neutralizing antibodies are present that prevent microbes from infecting further cells and provide protection against re-infection.
CTL are therefore important to limit the spread of viral infection before sufficient titers of protective antibodies become available. Thus, a CTL response against infections must be induced within a few days, should be robust, effective and induce a long-term memory response. In this project, we aim to improve immunotherapeutic vaccination approaches by combining distinct adjuvants in different viral models and identify the underlying molecular mechanisms.
2. Combining different adjuvants to improve vaccines against tumors
We have shown previously that combining an antigen with different adjuvants results in synergistically enhanced CD8+ T cell responses, by mechanisms involving the different chemokine receptors, but also signal 1, 2 and 3. These findings provide a promising approach of novel quality for designing better vaccines against tumors. However, tumors learn to evade the immune system and the balance between suppressive and effector immune cells is important to control tumor growth. In this project, we aim to improve immunotherapeutic vaccination approaches in different tumor models.