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Publications of the Week

N-Terminal Domain Antigenic Mapping Reveals a Site of Vulnerability for SARS-CoV-2

By March 24, 2021No Comments

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This week, we profile a recent publication in Cell from David Veesler (pictured) at UW.

Can you provide a brief overview of your lab’s current research focus?

The focus of the Veesler lab is to decipher the structure and function of macromolecular complexes involved in the pathogenesis of infectious diseases to provide avenues for creating vaccines and therapeutics. Over the past year, the lab has focused on the SARS-CoV-2 spike protein and the determinants of antibody-based immunity against SARS-CoV-2.

What is the significance of the findings in this publication?

We show that there is a poorly studied spot on the SARS-CoV-2 spike protein that antibodies bind to that prevents infection. This information is useful for the development of the next generation of SARS-CoV-2 vaccines. In other words, including this spot in a vaccine could increase the power of the vaccine. We also provide evidence that the virus is already evolving to avoid antibodies that bind to this spot. This information provides context for the emergence of several mutations that have appeared in the variants-of-concern.

What are the next steps for this research?

At this point, we’re interested in surveying and characterizing the mutations that are emerging in the variants-of-concern. We are trying to understand what these mutations mean in terms of vaccine-mediated immunity, for example. Discovering additional spots on SARS-CoV-2 that might not be as susceptible to these mutations is also an on-going objective.

This work was funded by:

The research on the N-terminal domain antibodies was supported by the National Institute of General Medical Sciences (R01GM120553), National Institute of Allergy and Infectious Diseases (DP1AI158186 and HHSN272201700059), a Pew Biomedical Scholars Award, Investigators in the Pathogenesis of Infectious Disease Awards from the Burroughs Wellcome Fund, Fast Grants, the Natural Sciences and Engineering Research Council of Canada, the Pasteur Institute, the University of Washington Arnold and Mabel Beckman cryoEM Center, and beamline 5.0.2 at the Advanced Light Source at Lawrence Berkley National Laboratory.

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