Development of protein nanovacins that self-structure against SARS-Cov-2

The sudden appearance of a new viral pneumonia in China at the end of 2019 was the beginning of a series of events that took the world to a pandemic that in three months infected more than a million people around the world and reached more than 200 countries and territories. The SARS-CoV-2 virus, from the same Coronaviridae family to which the SARS and MERS viruses belong, triggers a severe acute respiratory condition that leads to death in approximately 2% of cases. The COVID-19 disease has already generated immeasurable global impacts and it is believed that it will only be properly contained through the development of vaccines, since we can face new waves of dissemination when suppression measures are suspended, which makes vaccines a top priority. according to the World Health Organization. In a scenario so fragile that it involves the need to give priority vaccination to risk groups, it is necessary to prioritize safer vaccination strategies, such as subunit vaccines. The low immunogenicity frequently observed in this strategy can be countered with the use of nanoparticles that allow a multivalent presentation of antigens, thus generating a more robust immune response. In this project, we propose the use of SAPN (Self Assembling Protein Nanoparticles) nanovaccines, in which the protein antigen is modified by the fusion of short peptide sequences that self-structure in nanoparticles (NPs) of approximately 100 nm under physical-chemical conditions appropriate. Such an approach mimics the disposition of antigens from a viral particle and has already been used in our group in a Zika model, inducing a strong antigen-specific humoral response. Different SARS-CoV-2 structural antigens will be selected to be transformed into nanovacins by the proposed strategy, which will be used to induce immune responses (antibodies) with the ability to inhibit viral infection in vitro for subsequent tests in a murine model. As additional advantages, these nanovacins have better stability and high internalization capacity, as they have peptides that act as membrane-active peptides, thus mimicking characteristics of size and behavior typical of the viral particle, which may even favor cellular immunity. We therefore hope to develop an innovative vaccine strategy that can significantly contribute to this epidemic and will soon be considered a promising tool to limit the progress of COVID-19.