Figure 2.

DNA vaccines targeting SARS-CoV-2 can be created through recombinant DNA technology, utilizing the commercially available pcDNA3.1-SARS2-Spike plasmid (e.g., obtained from Addgene, MA) as the template. A DNA plasmid encoding the extracellular domain of the spike protein is loaded into a lipid nanoparticle (LNP). Next, the production of LNP-protein corona DNA vaccines will follow, achieved by incubating DNA-loaded LNPs with donor-derived interstitial fluid (DIF) obtained from healthy human volunteers, employing standardized protocols. The protein corona will consist of numerous proteins, here represented by a single green protein for simplicity. Our focus will shift toward exploiting the protein corona as a natural targeting entity, with particular attention to certain proteins, known as protein corona fingerprints (PCFs), which hold promise as potential targeting ligands. The internalization of LNP-protein corona DNA vaccines into target cells, such as antigen-presenting cells (APCs) and dendritic cells (DCs), ensues via a receptor-mediated mechanism. Protein corona fingerprints lock onto receptors of APCs stimulating massive vaccine internalization, which then churns out copies of the virus’s spike protein. Activation of adaptive immunity leads to the production of neutralizing antibodies and cell-mediated immune responses against SARS-CoV-2. For simplicity, the cell-mediated immune response is not depicted in the figure, but for a complete description, the reader may refer to.³⁹