Emerging evidence suggests that mucosal immunity plays an important role in the control of respiratory infections and may also shape the prognosis of lung tumors. To induce mucosal immune responses by vaccination, suitable vaccine platforms that deliver antigens to mucosal sites are required. Due to their evolved mechanisms for cell entry and delivery of genetic material to host cells, viral vectors are well-suited modalities for delivering vaccine antigen sequences. Currently, the repertoire of viral vectors for mucosal vaccinations is limited to only few platforms that also demonstrated limitations in clinical studies. Therefore, novel viral vector platforms for mucosal vaccinations are required.
In a rational screen for a new technology, we identified an exotic virus for such a platform. We will incorporate different antigens from SARS-CoV-2 into the viral genome, which either aim at eliciting neutralizing antibody responses (spike) or protective T cell responses (nucleoprotein, envelope protein, non-structural proteins). In challenge experiments, these different vectors will therefore also provide insights to correlates of protection against SARS-CoV-2 infection. As these antigens also differ profoundly in length, their integration into the viral genome will also reveal the packaging capacity of the new viral vector system.
Next to the application of the mucosal vaccine platform in the context of respiratory infections, we will also assess its potential as immunotherapeutic modality in the treatment of lung cancer. To this end, we will incorporate tumor associated antigens of a murine cancer model into the vector. Via the intranasal application of this viral vector, we aim to induce tumor-specific tissueresident memory T cells in the respiratory tract, which have been associated with positive prognostic outcomes in lung cancer patients.
In conclusion, the establishment of a novel mucosal vaccine platform against both respiratory infections and lung malignancies is the main goal of the present project and might represent an important step towards harnessing the potential of mucosal immunity.
