Addressing gaps in our understanding of the mucosal immune response to SARS-CoV-2: Implications for transmission.

Significant progress has been made in our understanding of systemic immunity to SARS-CoV-2, the virus that causes COVID-19. However much less is known about the mucosal immune response in the upper respiratory tract (the nose, mouth and throat). Based on data from our lab, we can detect antibodies to SARS-CoV-2 in the saliva of COVID-19 patients, and in some cases these antibodies bear the hallmarks of being produced in the local mucosal tissues. Prior to COVID we also discovered that antibody producing cells, particularly those produced at mucosal sites, can move about the body. However, in the context of SARS-CoV-2, we do not know how the mucosal immune response to natural infection is initiated, whether it is durable (maintained over time) and if it is effective at preventing asymptomatic infection against the "original" form of SARS-CoV-2 or its variants. We also don't know how vaccine-induced immunity in the upper respiratory tract compares with natural immunity. A better understanding of these questions is critical for predicting whether natural or vaccine-induced immunity prevents transmission against SARS-CoV-2 and its variant strains. In this study, we will take two approaches for addressing these gaps in knowledge. The first is to use an animal model to understand residence and trajectory of antibody producing cells in response to a de novo infection with SARS-CoV-2, or a recall response to SARS-CoV-2 in a pre-immune animal (conferred through natural immunity or vaccination). The advantage of the animal model is that we can assess antibody producing cells in different tissues of the body including the salivary glands, the lungs, the bone marrow and the gut. The second approach is to examine the mucosal immune response to SARS-CoV-2 in human populations that are highly exposed to the virus. Collectively these experiments will close gaps in our understanding of the mucosal immune response to SARS-CoV-2.