1610712021 Epsilon variant mutations contribute fo COVID immune evasion ~ ScienceDaily
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Epsilon variant mutations contribute to COVID immune evasion
Date: July 6, 2021
Source: University of Washington School of Medicine/UW Medicine
Summary: _ New studies reveal an unprecedented mechanism behind the loss of antibody neutralization
against this pandemic coronavirus variant of concem.
Shae: f W Pin |
FULL STORY
Three mutations in the Epsilon coronavirus spike protein dampen the neutralizing
potency of antibodies induced by current vaccines or past COVID infections.
The mutations give this coronavirus variant of concer a means to totally evade specific monoclonal antibodies
used in clinics and reduce the effectiveness of antibodies from the plasma of vaccinated people.
To better understand the exact immune escape strategies at work here, the scientists visualized this variant's
infection machinery to see what is different from the original configuration of the pandemic coronavirus, and
what the implications of these changes are
The international project was led by David Veesler's lab in the Department of Biochemistry at the University of
Washington in Seattle and by Luca Piccoli and Davide Corti of Vir Biotechnology.
For several years, the Veesler lab and its collaborators have been exploring the molecular conformation and
infection mechanics of SARS-like coronaviruses. They also examine how antibodies attempt to block infection
mechanisms, and how variants come up with new dodges.
Their latest data shows that the Epsilon variant "relies on an indirect and unusual neutralization-escape
strategy,” according to the researchers.
Their findings are published as a First Release paper in Science.
‘A molecular clock analysis timed the emergence of the precursor to the Epsilon variant to May of 2020 in
California. By summer of 2020 it had diverged into its B. 1.427/8.1.429 lineages. COVID cases from the variant
increased quickly, and the variant soon became widespread in the United States. It has now been reported in
at least 34 other countries.
To lear more about the characteristics of the Epsilon variant, the researchers tested the resilience against the
Epsilon variant of plasma from people who were exposed the virus, as well as vaccinated people. The
neutralizing potency of the plasma against the Epsilon variant of concern was reduced about 2 to 3.5 fold.
hitpsslwwu.sciencedally.comireleases/2021107/210706003857.him 48‘e107/2021 Epsiton variant mutations contribute fo COVID immune evasion ~ ScienceDaily
Like the original SARS-CoV-2, the variant infects target cells through its spike glycoprotein -- the structure that
‘crowns the surface of the virus. The researchers found that the Epsilon mutations were responsible for
rearrangements in critical areas of the spike glycoprotein; electron cryomicroscopy studies showed structural
changes in these areas.
Visualizing these mutations helps explain why antibodies had difficulty binding to the spike glycoprotein
One of the three mutations in the Epsilon variant affected the receptor binding domain on the spike
glycoprotein. This mutation reduced the neutralizing activity of 14 out of 34 neutralizing antibodies specific to
that domain, including clinical stage antibodies.
‘The other two of the three mutations in the variant affected the N-terminal domain on the spike glycoprotein.
‘The researchers used mass spectrometry and structural analysis to find that a part of the coronavirus N-
terminal domain was remodeled by these mutations.
The signal peptide cleavage site was shifted in the NTD antigenic supersite, and a new disulphide bond was
formed. This resulted in a total loss of neutralization by 10 out of 10 antibodies tested specific to the N-terminal
domain in the spike glycoprotein
The scientist believed that uncovering mechanisms of immune evasion, such as this newfound mechanism
based on signal peptide modification, is as important as variant surveillance through RNA sequencing,
Together, they note, such efforts could help to successfully counter the ongoing pandemic,
The lead scientists on this project were Matthew McCallum and Alexandra C. Walls of the UW School of
Medicine Department of Biochemistry; Jessica Bassi and Anna de Marco of Humabs Biomed; and Alex Chen
of Vir Biotechnology.
This study was supported by the National Institute of Allergy and Infectious Diseases at the National institutes
of Health, Pew Biomedical Scholars Award, Investigators in the Pathogenesis of Infectious Disease Awards
from the Burroughs Wellcome Fund, Fast Grants, Natural Sciences and Engineering Research Council of
Canada, and Pasteur Institute.
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hitpsslwwu.sciencedally.comireleases/2021107/210706003857.him
2151610712021 Epsilon variant mutations contribute fo COVID immune evasion ~ ScienceDaily
Story Source:
Materials provided by University of Washington School of Medicine/UW Medicine. Note: Content may be
edited for style and length.
Journal Reference:
1, Matthew McCallum, Jessica Bassi, Anna De Marco, Alex Chen, Alexandra C. Walls, Julia Di luli, M
Alejandra Tortorici, Mary-Jane Navarro, Chiara Silacci-Fregni, Christian Saliba, Kaitlin R. Sprouse, Maria
Agostini, Dora Pinto, Katja Culap, Siro Bianchi, Stefano Jaconi, Elisabetta Cameroni, John E. Bowen,
Sasha W Tilles, Matteo Samuele Pizzuto, Sonja Bernasconi Guastalla, Giovanni Bona, Alessandra
Franzetti Pellanda, Christian Garzoni, Wesley C. Van Voorhis, Laura E, Rosen, Gyorgy Snell, Amalio.
Telenti, Herbert W. Virgin, Luca Piccoli, Davide Corti, David Veesler. SARS-CoV-2 immune evasion by
the B.1.427/B.1.429 variant of concern. Science, 2021; eabi7994 DOI: 10.1126/science.abi7994
Cite This Page: MLA APA Chicago
University of Washington Schoo! of Medicine/UW Medicine. “Epsilon variant mutations contribute to COVID
immune evasion.” ScienceDaily. ScienceDaily, 6 July 2021
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