Core B: Virology Core

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PROJECT SUMMARY – CORE B: VIROLOGY Zoonotic coronaviruses (CoV) are responsible for three major epidemics/pandemics in the 21st century, including Severe Acute Respiratory Coronavirus (SARS-CoV) in 2003 and Middle East Respiratory coronavirus (MERS- CoV) in 2012. In December 2019 a third novel coronavirus designated SARS-CoV-2 emerged in Wuhan China, and in the space of 18 months has caused over 170 million cases and 3,500,000 deaths in more than 220 countries. About one-sixth of these total cases have been reported in the US, resulting in over 600,000 deaths. Of concern, multiple distinct SARS-like and MERS-like CoV strains reside in bats and other species and are poised to emerge in the future, creating a critical need for broadly protective vaccines. We seek to develop a pan-betacoronavirus vaccine that will universally protect against viruses from the sarbecovirus, merbecovirus, and embecovirus subgenera. The goals of Core B (Virology, Baric) are to: i) provide group sarbecovirus, merbecovirus, and embecovirus animal models of human disease for evaluating vaccine performance; ii) develop reverse genetic platforms, recombinant viruses, and animal models to other high risk zoonotic coronaviruses; iii) evaluate virus evolution in the expanding SARS-CoV-22 pandemic and create appropriate reagents to evaluate pan-betacoronavirus vaccine performance in vivo; and iv) evaluate the mechanisms regulating protective or pathogenic immune responses after homologous (i.e., vaccine-strain) and heterologous challenge. The overall goal is to identify high-performance pan-sarbecovirus and pan-betacoronavirus vaccine candidates that provide robust protective immune responses in at least two animal models.