The main aim of this project is the development and validation of a nanoparticle-based DNA vaccine against SARS-CoV-2. To this end, several variants of DNA vaccines will be designed in order to make express the S1 subunit of the SARS-CoV-2 spike protein or its most antigenic portions into host transfected cells with the final aim to induce a specific antiviral immune response and the production of neutralizing antibodies. The most promising DNA vaccine candidates will be incorporated within lipid NPs grafted with artificial human protein coronas. With respect to traditional DNA vaccines, the use of corona-coated lipid NPs as vaccine delivery platform will enable to: i) protect DNA vaccine from extracellular degradation; ii) exploit the artificial protein corona to boost cellular uptake by keratinocytes and Antigen Presenting Cells (APCs) following cutaneous administration; iii) enhance endo/lysosomal escape of DNA and facilitate nuclear delivery.
