Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

mRNA-1273 vaccine induces neutralizing antibodies against spike mutants from global SARS-CoV-2 variants

Kai Wu, Anne P. Werner, Juan I. Moliva, Matthew Koch, Angela Choi, Guillaume B. E. Stewart-Jones, Hamilton Bennett, Seyhan Boyoglu-Barnum, Wei Shi, View ORCID ProfileBarney S. Graham, Andrea Carfi, Kizzmekia S. Corbett, Robert A. Seder, Darin K. Edwards
doi: https://doi.org/10.1101/2021.01.25.427948
Kai Wu
1Moderna Inc., Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Anne P. Werner
2National Institutes of Health, National Institute of Allergy and Infectious Diseases, Vaccine Research Center, Bethesda, MD, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Juan I. Moliva
2National Institutes of Health, National Institute of Allergy and Infectious Diseases, Vaccine Research Center, Bethesda, MD, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Matthew Koch
1Moderna Inc., Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Angela Choi
1Moderna Inc., Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Guillaume B. E. Stewart-Jones
1Moderna Inc., Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hamilton Bennett
1Moderna Inc., Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Seyhan Boyoglu-Barnum
2National Institutes of Health, National Institute of Allergy and Infectious Diseases, Vaccine Research Center, Bethesda, MD, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Wei Shi
2National Institutes of Health, National Institute of Allergy and Infectious Diseases, Vaccine Research Center, Bethesda, MD, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Barney S. Graham
2National Institutes of Health, National Institute of Allergy and Infectious Diseases, Vaccine Research Center, Bethesda, MD, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Barney S. Graham
Andrea Carfi
1Moderna Inc., Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kizzmekia S. Corbett
2National Institutes of Health, National Institute of Allergy and Infectious Diseases, Vaccine Research Center, Bethesda, MD, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Robert A. Seder
2National Institutes of Health, National Institute of Allergy and Infectious Diseases, Vaccine Research Center, Bethesda, MD, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Darin K. Edwards
1Moderna Inc., Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: darin.edwards@modernatx.com
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

ABSTRACT

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the causative infection of a global pandemic that has led to more than 2 million deaths worldwide. The Moderna mRNA-1273 vaccine has demonstrated ~94% efficacy in a Phase 3 study and has been approved under Emergency Use Authorization. The emergence of SARS-CoV-2 variants with mutations in the spike protein, most recently circulating isolates from the United Kingdom (B.1.1.7) and Republic of South Africa (B.1.351), has led to lower neutralization from convalescent serum by pseudovirus neutralization (PsVN) assays and resistance to certain monoclonal antibodies. Here, using two orthogonal VSV and lentivirus PsVN assays expressing spike variants of 20E (EU1), 20A.EU2, D614G-N439, mink cluster 5, B.1.1.7, and B.1.351 variants, we assessed the neutralizing capacity of sera from human subjects or non-human primates (NHPs) that received mRNA-1273. No significant impact on neutralization against the B.1.1.7 variant was detected in either case, however reduced neutralization was measured against the mutations present in B.1.351. Geometric mean titer (GMT) of human sera from clinical trial participants in VSV PsVN assay using D614G spike was 1/1852. VSV pseudoviruses with spike containing K417N-E484K-N501Y-D614G and full B.1.351 mutations resulted in 2.7 and 6.4-fold GMT reduction, respectively, when compared to the D614G VSV pseudovirus. Importantly, the VSV PsVN GMT of these human sera to the full B.1.351 spike variant was still 1/290, with all evaluated sera able to fully neutralize. Similarly, sera from NHPs immunized with 30 or 100μg of mRNA-1273 had VSV PsVN GMTs of ~ 1/323 or 1/404, respectively, against the full B.1.351 spike variant with a ~ 5 to 10-fold reduction compared to D614G. Individual mutations that are characteristic of the B.1.1.7 and B.1.351 variants had a similar impact on neutralization when tested in VSV or in lentivirus PsVN assays. Despite the observed decreases, the GMT of VSV PsVN titers in human vaccinee sera against the B.1.351 variant remained at ~1/300. Taken together these data demonstrate reduced but still significant neutralization against the full B.1.351 variant following mRNA-1273 vaccination.

Competing Interest Statement

K. Wu, G. Stewart-Jones, M. Koch, A. Choi, H. Bennett, A. Carfi, and D. Edwards are employed by ModernaTX, Inc., B. S. Graham and K. S. Corbett are inventors on the following Patent Applications: EP Patent Application 17800655.7 filed 13 May 2019, entitled Prefusion coronavirus spike proteins and their use; US Patent Application 16/344,774 filed 24 April 2019 entitled Prefusion coronavirus spike proteins and their use [HHS Ref. No. E-234-2016-1-US-03]. B. S. Graham and K. S. Corbett are inventors on the following Patent Application: US Provisional Patent Application 62/972,886 filed 11 February 2020 entitled 2019-nCoV Vaccine.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Back to top
PreviousNext
Posted January 25, 2021.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
mRNA-1273 vaccine induces neutralizing antibodies against spike mutants from global SARS-CoV-2 variants
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
mRNA-1273 vaccine induces neutralizing antibodies against spike mutants from global SARS-CoV-2 variants
Kai Wu, Anne P. Werner, Juan I. Moliva, Matthew Koch, Angela Choi, Guillaume B. E. Stewart-Jones, Hamilton Bennett, Seyhan Boyoglu-Barnum, Wei Shi, Barney S. Graham, Andrea Carfi, Kizzmekia S. Corbett, Robert A. Seder, Darin K. Edwards
bioRxiv 2021.01.25.427948; doi: https://doi.org/10.1101/2021.01.25.427948
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
mRNA-1273 vaccine induces neutralizing antibodies against spike mutants from global SARS-CoV-2 variants
Kai Wu, Anne P. Werner, Juan I. Moliva, Matthew Koch, Angela Choi, Guillaume B. E. Stewart-Jones, Hamilton Bennett, Seyhan Boyoglu-Barnum, Wei Shi, Barney S. Graham, Andrea Carfi, Kizzmekia S. Corbett, Robert A. Seder, Darin K. Edwards
bioRxiv 2021.01.25.427948; doi: https://doi.org/10.1101/2021.01.25.427948

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Immunology
Subject Areas
All Articles
  • Animal Behavior and Cognition (4087)
  • Biochemistry (8762)
  • Bioengineering (6479)
  • Bioinformatics (23341)
  • Biophysics (11750)
  • Cancer Biology (9149)
  • Cell Biology (13248)
  • Clinical Trials (138)
  • Developmental Biology (7417)
  • Ecology (11369)
  • Epidemiology (2066)
  • Evolutionary Biology (15087)
  • Genetics (10399)
  • Genomics (14009)
  • Immunology (9121)
  • Microbiology (22040)
  • Molecular Biology (8779)
  • Neuroscience (47368)
  • Paleontology (350)
  • Pathology (1420)
  • Pharmacology and Toxicology (2482)
  • Physiology (3704)
  • Plant Biology (8050)
  • Scientific Communication and Education (1431)
  • Synthetic Biology (2208)
  • Systems Biology (6016)
  • Zoology (1249)