Development of SARS-CoV-2 auto-assembly protein-based nanovaccines

Abstract

The sudden appearance of a new viral pneumonia in late 2019 was the first of a series of events that led the world to a pandemic that in only 3 months has infected over one million people and reached over 200 countries and territories. The virus, named SARS-CoV-2, from the Coronaviridae family just like SARS and MERS, triggers a severe acute respiratory disease that leads to death in approximately 2% of the cases. The disease COVID-19 has already caused unmeasurable global impacts and is likely to be contained only through the development of vaccines, since new waves of infection may occur once suppression measurements are suspended. The World Health Organization states that vaccines are now a major priority in this battle. In such a fragile scenario that involves the need to vaccinate as soon as possible people belonging to the risk groups, safer strategies such as subunit vaccines should be a priority. The low immunogenicity frequently associated with this strategy can be counteracted by the use of nanoparticles that allow a multivalent antigen presentation, leading to a more robust immunological response. In the present project, we propose the use of SAPN (Self Assembling Protein Nanoparticles) strategy to develop the nanovaccines, which consists in modifying the protein antigen with the fusion of short peptide sequences that promote self-assembly in nanoparticles (NP) of around 100 nm in adequate physicochemical conditions. Such strategy mimics the antigen display of a viral particle and is currently being used by our group in a ZIKV model, inducing a strong antigen-specific humoral response. Different structural antigens of SARS-CoV-2 will be selected to be transformed into nanovaccines through the proposed strategy, which will be used to induce protective immunological responses (antibodies) capable to inhibit virus infectivity at in vitro conditions and, subsequently, protective immunity in murine model. As a plus, these nanovaccines also present improved stability and higher internalization capacity, since they have in their structure peptides that act as Cell Penetrating Peptides, thus mimicking not only the size but also the behavior of viral particles, what can favor cellular immunity. We seek to develop an innovative vaccine strategy that can strongly contribute to this pandemic and be shortly considered a promising tool to be used to limit COVID-19 spread. (AU)