Project 455125

As of October 2021, the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID19), has infected hundreds of million of people and caused almost 5 million deaths worldwide, with many more suffering from long-term effects post-infection. The ongoing pandemic has had devastating societal and economic effects globally. The emergence of more variants is inevitable as the virus continues to infect vulnerable populations worldwide. Although highly effective vaccines have been developed, the recent emergence and rapid takeover of highly transmissible variants is complicating control efforts. Therefore, a better understanding of the molecular underpinnings that cause infection in individuals vaccinated against SARS-CoV-2 is crucial to implement additional preventative or therapeutic interventions. The innate immune system forms the first line of defense against invading pathogens, and viruses that cause disease can efficiently prevent innate immune responses to overwhelm this barrier. Currently, our understanding of how variants of concern (VOCs) are able to overcome early immune responses in vaccinated individuals is limited. The research goals of this project are to determine the characteristics of VOCs that allow for increased virus spread from host-to-host, and how early immune detection and activation are manipulated by virus infection to cause disease in vaccinated individuals in both animal and human models. In addition, we will investigate which immune features lead to greater disease severity in VOC infections, as disease severity and outcomes of infection with SARS-CoV-2 are correlated with high levels of inflammation rather than viral load.