Regulation of coronavirus cross-reactivity and immune durability for pan-coronavirus vaccine development

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. Immune protection generated after coronavirus infection or vaccination is also short-lived adding further opportunity for new infections and continue disease burden. Next generation pan-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 in the Germinal Center (GC) to induce broadly reactive antibodies and long-lived immune memory will be defined during coronavirus infection. To complement the immunological studies, the parts of the virus that stimulate a more cross-protective response will also be identified. This information will then be applied to the evaluation of my novel pan-sarbecovirus vaccine candidates. These candidates were developed on a trivalent protein subunit platform and are formulated with squalene-in-water emulsion (SWE) adjuvant. 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.