Development of mutation-robust vaccines and antibodies, and their implications for the evolution of SARS-CoV-2

COVID-19 has caused over 774 million cases and 7.02 million deaths worldwide as of February, 2024. The causative RNA virus, SARS-CoV-2, has the ability to rapidly mutate genetically, and these mutations allow it to swiftly infect with increased efficacy and/or severity. These mutations are of concern because they allow SARS-CoV-2 to evade not only antibodies formed by natural infection or vaccines, but also recombinant antibody therapeutics. With new variants emerging roughly every other month, it will not be long before the current repertoire of antibodies and vaccines against SARS-CoV-2 becomes obsolete. Although it is difficult to predict the mutations in the next variant, it is possible with current technologies to examine potential mutations and the activity of such mutated variants. In this proposal, we will test the robustness of mutation-tolerant de novo vaccines and antibodies against SARS-CoV-2. We also seek to understand how SARS-CoV-2 evolves over time and to decipher the mechanism of antigenic escape from diverse antibodies. This platform can guide us in the design of better therapeutics to combat current and future variants of SARS-CoV-2, and other viruses.