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.
There is evidence that all the limitations of DNA vaccines can be overcome by using advanced gene delivery technologies. Properly structured nano-sized particles (e.g. nanoparticles (NP)) may stabilize DNA formulations, avoid DNA degradation, facilitate targeted and controlled delivery to APC, enable efficient transfection and, in turn, enhance immunogenicity.
This project employs a novel approach for the development of a vaccine against SARS-Cov-2, as it relies on the design, optimization and validation of smart LNPs exploiting the protein corona effect for targeted drug delivery. This concept has not been explored so far and to this end, manifold research fields (such as physics, chemistry, biology, material sciences) are needed.
The proposed research is not incremental, since the employment of protein corona-coated LNPs as vehicles of vaccines against coronaviruses is a completely new idea and basic knowledge in this field still has to be developed.