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Principal Investigator: Jie Sun
Organization: UNIVERSITY OF VIRGINIA
Fiscal Year: 2023
Award: $707,188
Funding agency: National Institute of Allergy and Infectious Diseases
PROJECT SUMMARY/ABSTRACT
In the wake of a global pandemic caused by the ancestral strain of SARS-CoV-2, infections with emerging variant
strains are an ongoing cause of morbidity and mortality. Robust respiratory mucosal immune responses to
SARS-CoV-2 infection and/or vaccination are vital to prevent re-infection and complications of emerging variant
strains. Children with poorly controlled, Th2-mediated asthma treated with high-dose corticosteroids are an
important at-risk population for hospitalization with variant strains of SARS-CoV-2, often in association with
seasonal respiratory viral co-infections. Although children mount durable systemic adaptive immune responses
to SARS-CoV-2 infection and/or vaccination, very little is known as to whether Th2 inflammation present in the
lungs of many children with asthma dysregulates the lower respiratory mucosal adaptive immune response to
the ancestral virus and its variant strains. Therefore, the broad goal of this proposal is to examine blood and
lower respiratory adaptive mucosal immune signatures, including spike (S) and receptor-binding domain (RBD)
antibodies, neutralizing antibodies, and T and B cell responses to previous infection with SARS-CoV-2 and
variant strains (Specific Aim One) and/or mRNA vaccination (Specific Aim Two) in children with asthma and
healthy controls. We will furthermore interrogate significant determinants of humoral and T cell adaptive immune
response variables with generalized linear models to identify those determinants which most inform adaptive
responses. To further examine mechanisms of allergen-induced inflammation on adaptive immunity to SARS-
CoV-2 and variants in the blood and lungs, we will (Specific Aim Three) infect juvenile K18-hACE2 mice
sensitized to house dust mite in the presence and absence of corticosteroid treatment and mRNA vaccination.
New knowledge from these studies should increase the understanding of adaptive immunity to SARS-CoV-2
infection and/or vaccination in children in a way to advance anti-viral treatment, isolation measures, and
development of novel booster vaccines targeting mucosal immunity. We are prepared to accomplish these aims
through an established team of investigators with experience in childhood asthma and bronchoscopy, in
partnership with immunologists with expertise in the investigation of respiratory mucosal immunity to SARS-CoV-
2 infection and mRNA vaccination.
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