SARS-CoV-2 Omicron BA.2 Variant Evades Neutralization by Therapeutic Monoclonal Antibodies
Zhou et al.,
SARS-CoV-2 Omicron BA.2 Variant Evades Neutralization by Therapeutic Monoclonal Antibodies,
bioRxiv, doi:10.1101/2022.02.15.480166 (Preprint) (In Vitro)
In Vitro study showing that omicron BA.2 evades all monoclonal antibodies tested, including sotrovimab and tixagevimab/cilgavimab which retained activity for omicron BA.1.
4 In Vitro studies support the efficacy of sotrovimab
[Liu, Sheward, VanBlargan, Zhou].
Zhou et al., 16 Feb 2022, preprint, 4 authors.
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
Abstract: bioRxiv preprint doi: https://doi.org/10.1101/2022.02.15.480166; this version posted February 16, 2022. The copyright holder for this preprint
(which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission.
SARS-CoV-2 Omicron BA.2 Variant Evades Neutralization by
Therapeutic Monoclonal Antibodies
Hao Zhou1,*, Takuya Tada1,*, Belinda M. Dcosta1,* and Nathaniel R.
Landau1,#
Affiliation:
1
Department of Microbiology, NYU Grossman School of Medicine, New York, NY, USA.
*These authors contributed equally.
#Corresponding author:
Nathaniel R. Landau, Ph.D.
NYU Grossman School of Medicine
430 East 29th Street, Alexandria West Building, Rm 509, New York, NY 10016
Email: nathaniel.landau@med.nyu.edu
Phone: (212) 263-9197
1
bioRxiv preprint doi: https://doi.org/10.1101/2022.02.15.480166; this version posted February 16, 2022. The copyright holder for this preprint
(which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission.
Keywords: SARS-CoV-2 variants, Omicron BA.2, monoclonal antibodies, spike protein,
Sotrovimab, Evusheld.
2
bioRxiv preprint doi: https://doi.org/10.1101/2022.02.15.480166; this version posted February 16, 2022. The copyright holder for this preprint
(which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission.
Abstract
Monoclonal antibody therapy for the treatment of SARS-CoV-2 infection has been highly
successful in decreasing disease severity; however, the recent emergence of the
heavily mutated Omicron variant has posed a challenge to this treatment strategy. The
Omicron variant BA.1 has been found to evade neutralization by the Regeneron and Eli
Lilly therapeutic monoclonal antibodies, while Sotrovimab and the Evusheld monoclonal
antibody cocktail retain significant neutralizing activity. A newly emerged variant,
Omicron BA.2, containing the BA.1 mutations plus an additional 6 mutations and 3
deletions, 3 of which lie in the receptor binding domain, has been found to be spreading
with increased transmissibility.
We report here, using a spike protein-pseudotyped
lentivirus assay, that Omicron BA.2 is not neutralized with detectable titer by any of the
therapeutic monoclonal antibodies, including Sotrovimab and the Evusheld monoclonal
antibodies. The results demonstrate the difficulty of identifying broadly neutralizing
monoclonal antibodies against SARS-CoV-2 and the importance of the T cell response
from which immunoevasion is more difficult.
3
bioRxiv preprint doi: https://doi.org/10.1101/2022.02.15.480166; this version posted February 16, 2022. The copyright holder for this preprint
(which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission.
Main text
The BA.2 variant of the highly mutated Omicron SARS-CoV-2 variant identified in late
2021 in patients in countries including Denmark, South Africa and India (1) and since
then, in more countries including the United States. BA.2 has been found to be 1.5-fold
more transmissible than the already highly transmissible BA.1 variant and is thus
expected to continue to increase in prevalence (2). The BA.2 spike protein has all of the
mutations of BA.1 plus an additional 6 mutations and 3 deletions, three of which lie in
the receptor binding domain (3) (Supplemental Figure 1A). Of the monoclonal
antibodies authorized by the Food and..
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