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SARS-CoV-2 Variant B.1.1.7 is Susceptible to Neutralizing Antibodies Elicited by Ancestral Spike Vaccines

45 Pages Posted: 1 Feb 2021 Publication Status: Published

See all articles by Xiaoying Shen

Xiaoying Shen

Duke University - Duke Human Vaccine Institute

Haili Tang

Duke University - Department of Surgery

Charlene McDanal

Duke University - Department of Surgery

Kshitij Wagh

Los Alamos National Laboratory - Theoretical Biology and Biophysics

Will M. Fischer

Los Alamos National Laboratory - Theoretical Biology and Biophysics

James Theiler

Los Alamos National Laboratory - Theoretical Biology and Biophysics

Hyejin Yoon

Los Alamos National Laboratory - Theoretical Biology and Biophysics

Dapeng Li

Duke University School of Medicine - Duke Human Vaccine Institute

Barton F. Haynes

Duke University - Duke Human Vaccine Institute

Kevin O. Saunders

Duke University School of Medicine - Duke Human Vaccine Institute

S. Gnanakaran

Los Alamos National Laboratory - Theoretical Biology and Biophysics

Nicolas W. Hengartner

Los Alamos National Laboratory - Theoretical Biology and Biophysics

Rolando Pajon

Moderna, Inc.

Gale Smith

Novavax, Inc.

Filip Dubovsky

Novavax, Inc.

Gregory M. Glenn

Novavax, Inc.

Bette T. Korber

Los Alamos National Laboratory - Theoretical Biology and Biophysics

David C. Montefiori

Duke University School of Medicine - Duke Human Vaccine Institute

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Abstract

The SARS-CoV-2 Spike glycoprotein mediates virus entry and is a major target for neutralizing antibodies. All current vaccines are based on the ancestral Spike with the goal of generating a protective neutralizing antibody response. Several novel SARS-CoV-2 variants with multiple Spike mutations have emerged, and their rapid spread and potential for immune escape have raised concerns. One of these variants, first identified in the United Kingdom, B.1.1.7 (also called VUI202012/01), contains eight Spike mutations with potential to impact antibody therapy, vaccine efficacy and risk of reinfection. Here we employed a lentivirus-based pseudovirus assay to show that variant B.1.1.7 remains sensitive to neutralization, albeit at moderately reduced levels (~2-fold), by serum samples from convalescent individuals and recipients of two different vaccines based on ancestral Spike: mRNA-1273 (Moderna) and protein nanoparticle NVX-CoV2373 (Novavax). Some monoclonal antibodies to the receptor binding domain (RBD) of Spike were less effective against the variant while others were largely unaffected. These findings indicate that B.1.1.7 is not a neutralization escape variant that would be a major concern for current vaccines, or for an increased risk of reinfection.

Funding: Original data and specimens for Protocol 20-0003 were supported by the Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases. KW and BK were supported by LANL LDRD 20190441ER. DCM, XS, HT, and CM were supported bythe COVID-19 Prevention Network (CoVPN) and the National Institute of Health. DL, BFH, and KOS were supported by a grant from the State of North Carolina from federal CARES Act funds, and NIAID grant AI142596.

Conflict of Interest: Rolando Pajon is an employee of Moderna, Inc. Filip, Dubovsky, Gale Smith and Gregory M. Glenn are employees of Novavax, Inc. The remaining authors have no competing interests.

Ethical Approval: Clinical trials described in this manuscript were approved by the appropriate Institutional Review Boards (IRBs).

Suggested Citation

Shen, Xiaoying and Tang, Haili and McDanal, Charlene and Wagh, Kshitij and Fischer, Will M. and Theiler, James and Yoon, Hyejin and Li, Dapeng and Haynes, Barton F. and Saunders, Kevin O. and Gnanakaran, S. and Hengartner, Nicolas W. and Pajon, Rolando and Smith, Gale and Dubovsky, Filip and Glenn, Gregory M. and Korber, Bette T. and Montefiori, David C., SARS-CoV-2 Variant B.1.1.7 is Susceptible to Neutralizing Antibodies Elicited by Ancestral Spike Vaccines. Available at SSRN: https://ssrn.com/abstract=3777473 or http://dx.doi.org/10.2139/ssrn.3777473
This version of the paper has not been formally peer reviewed.

Xiaoying Shen

Duke University - Duke Human Vaccine Institute ( email )

United States

Haili Tang

Duke University - Department of Surgery

100 Fuqua Drive
Durham, NC 27708-0204
United States

Charlene McDanal

Duke University - Department of Surgery

100 Fuqua Drive
Durham, NC 27708-0204
United States

Kshitij Wagh

Los Alamos National Laboratory - Theoretical Biology and Biophysics

Will M. Fischer

Los Alamos National Laboratory - Theoretical Biology and Biophysics

Los Alamos, NM 87545
United States

James Theiler

Los Alamos National Laboratory - Theoretical Biology and Biophysics

Los Alamos, NM 87545
United States

Hyejin Yoon

Los Alamos National Laboratory - Theoretical Biology and Biophysics

Dapeng Li

Duke University School of Medicine - Duke Human Vaccine Institute ( email )

Durham, NC 27710
United States

Barton F. Haynes

Duke University - Duke Human Vaccine Institute ( email )

United States

Kevin O. Saunders

Duke University School of Medicine - Duke Human Vaccine Institute ( email )

Durham, NC 27710
United States

S. Gnanakaran

Los Alamos National Laboratory - Theoretical Biology and Biophysics ( email )

Los Alamos, NM 87545
United States

Nicolas W. Hengartner

Los Alamos National Laboratory - Theoretical Biology and Biophysics ( email )

Los Alamos, NM 87545
United States

Rolando Pajon

Moderna, Inc. ( email )

United States

Gale Smith

Novavax, Inc. ( email )

Filip Dubovsky

Novavax, Inc. ( email )

Gregory M. Glenn

Novavax, Inc. ( email )

Bette T. Korber

Los Alamos National Laboratory - Theoretical Biology and Biophysics ( email )

Los Alamos, NM 87545
United States

David C. Montefiori (Contact Author)

Duke University School of Medicine - Duke Human Vaccine Institute ( email )

Durham, NC 27710
United States

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