Development of Epitope-Targeted SARS-CoV-2 Vaccines

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A vaccine against SARS-CoV2 is badly needed. We have developed a vaccine platform technology based on virus-like particles (VLPs) of RNA phages like MS2, PP7, AP205 and Qß. When displayed multivalently on these bionanoparticles, peptide and protein antigens acquire a high level of immunogenicity. They elicit high titer and long-lived antibody responses to virtually any displayed antigen. Moreover, the VLP platform has rapid response potential to quickly counter emerging threats. Here we describe an approach to the display of SARS-CoV2 epitopes, and tests of their ability to elicit neutralizing and protective antibodies in mice. Our approach consists of three specific aims: In Aim 1, we will Identify candidate vaccine epitopes for SARS-CoV2 and endow them with high immunogenicity by displaying them on VLPs. This virus shares sufficient sequence and structural homology with SARS-CoV1 to allow us to infer likely neutralizing epitopes from knowledge of the targets of its neutralizing antibodies. Accordingly, we describe strategies for display and optimization of spike protein epitopes we predict will elicit antibodies that will separately inhibit two essential steps in virus entry - receptor binding and virus-cell fusion. In Aim 2, we will immunize mice with candidate VLPs and will use ELISA to quantify the resulting antibody responses, testing the reaction of sera with recombinant spike protein and with synthetic peptides representing the chosen epitopes. In Aim 3, the neutralization activity of sera will be tested by plaque reduction neutralization tests in cultured cells. Subsequently, we will vaccinate mice transgenic for human ACE2 (the SARS-CoV2 receptor) and test their abilities to resist the effects of SARS-CoV2 infection.