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Principal Investigator: Taia Wang
Organization: STANFORD UNIVERSITY
Fiscal Year: 2022
Award: $439,325
Funding agency: National Cancer Institute
PROJECT 1: SUMMARY
As established through decades of research in protective immunity against infectious pathogens, achieving
durable immunity against SARS-CoV-2 will require specific functional properties of antibodies, B cells and T cells
that need to be defined through detailed repertoire studies. Antibody responses to viral infections in humans are
varied and of widely divergent clinical significance. Pre-existing, reactive antibodies or antibodies that are formed
early during infection can engage virus particles, forming immune complexes that may neutralize or mediate
clearance of the virus. On the other hand, immune complexes can also promote inflammation and exacerbate
symptoms of disease. SARS-CoV-2 infections can be asymptomatic or cause disease, COVID-19, which
manifests with a spectrum of symptoms ranging from mild to life threatening pneumonia and cytokine
dysregulation. The role of antibodies in protection against SARS-CoV-2 infections and whether antibodies may
play a role in promoting symptoms of COVID-19 remains unknown. In Project 1, we will define the heterogeneity
of antibody responses produced during SARS-CoV-2 infections and test the hypothesis that particular antibody
responses, with respect to the target antigen(s), specific epitopes and antibody effector functions, are required
for protection against SARS-CoV-2 infections. We will perform studies under the following specific aims: Aim 1:
Characterize antibodies elicited by SARS-CoV-2; Aim 2: Define antibody correlates of COVID-19 pathogenesis
and protection. These studies will include structure determination by cryo-electron microscopy that will delineate
the main binding epitopes and molecular characteristics of antibody recognition against the SARS-CoV-2 spike
protein. Further, we will investigate whether there are antibody profiles that correlate with more severe outcomes
in COVID-19. Results from these studies will guide the development of safe and effective vaccines and
monoclonal antibodies for the prevention and treatment of COVID-19.
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