Understanding mechanisms coronavirus cross-reactivity, immune durability, and pan-coronavirus vaccine protection

The COVID-19 (Coronavirus disease 2019) pandemic caused by the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is the largest public health crisis in modern history. Although COVID-19 vaccines have decreased disease burden, the current vaccines have limited coverage against new coronaviruses or SARS-CoV-2 variants and the COVID-19 vaccines do not offer long-lasting protection. Immune protection generated after coronavirus infection is also short-lived adding further opportunity for new infections and continue disease burden. Next generation coronavirus vaccines strive to achieve broad protection against several viruses at once over a longer period; however, the mechanisms driving broad and long-lived protection against coronaviruses are poorly understood. This project will determine the mechanisms driving broad protection and immune durability in the host against coronaviruses. Specifically, the mechanisms utilized by B cells to induce broadly reactive antibodies and long-lived immune memory will be defined during coronavirus infection. Additionally, our new trivalent protein subunit vaccine candidates formulated with squalene-in-water emulsion (SWE) adjuvant (Vaccine Formulation Institute) designed to broadly protect against SARS-CoV-2 variants and sarbecoviruses will be evaluated for their mechanisms of action and immune longevity. This work will bring understanding to the mechanisms of broad protection against coronaviruses and provide valuable evidence for the use of novel vaccines that may be more effective at combating the current coronavirus pandemic and preventing the next one.