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mRNA-1273 and BNT162b2 mRNA vaccines have reduced neutralizing activity against the SARS-CoV-2 Omicron variant

View ORCID ProfileVenkata-Viswanadh Edara, View ORCID ProfileKelly E. Manning, Madison Ellis, View ORCID ProfileLilin Lai, View ORCID ProfileKathryn M. Moore, View ORCID ProfileStephanie L. Foster, View ORCID ProfileKatharine Floyd, View ORCID ProfileMeredith E. Davis-Gardner, Grace Mantus, Lindsay E. Nyhoff, Sarah Bechnak, Ghina Alaaeddine, Amal Naji, Hady Samaha, Matthew Lee, Laurel Bristow, Laila Hussaini, Caroline Rose Ciric, Phuong-Vi Nguyen, View ORCID ProfileMatthew Gagne, Jesmine Roberts-Torres, Amy R. Henry, Sucheta Godbole, Arash Grakoui, Marybeth Sexton, Anne Piantadosi, Jesse J. Waggoner, View ORCID ProfileDaniel C. Douek, Evan J. Anderson, View ORCID ProfileNadine Rouphael, View ORCID ProfileJens Wrammert, View ORCID ProfileMehul S. Suthar
doi: https://doi.org/10.1101/2021.12.20.473557
Venkata-Viswanadh Edara
1Center for Childhood Infections and Vaccines of Children’s Healthcare of Atlanta, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA
2Emory Vaccine Center, Emory University, Atlanta, GA, USA
8Yerkes National Primate Research Center, Atlanta, GA, USA
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  • ORCID record for Venkata-Viswanadh Edara
Kelly E. Manning
1Center for Childhood Infections and Vaccines of Children’s Healthcare of Atlanta, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA
2Emory Vaccine Center, Emory University, Atlanta, GA, USA
8Yerkes National Primate Research Center, Atlanta, GA, USA
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Madison Ellis
1Center for Childhood Infections and Vaccines of Children’s Healthcare of Atlanta, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA
2Emory Vaccine Center, Emory University, Atlanta, GA, USA
8Yerkes National Primate Research Center, Atlanta, GA, USA
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Lilin Lai
1Center for Childhood Infections and Vaccines of Children’s Healthcare of Atlanta, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA
2Emory Vaccine Center, Emory University, Atlanta, GA, USA
8Yerkes National Primate Research Center, Atlanta, GA, USA
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Kathryn M. Moore
1Center for Childhood Infections and Vaccines of Children’s Healthcare of Atlanta, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA
2Emory Vaccine Center, Emory University, Atlanta, GA, USA
8Yerkes National Primate Research Center, Atlanta, GA, USA
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Stephanie L. Foster
1Center for Childhood Infections and Vaccines of Children’s Healthcare of Atlanta, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA
2Emory Vaccine Center, Emory University, Atlanta, GA, USA
8Yerkes National Primate Research Center, Atlanta, GA, USA
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Katharine Floyd
1Center for Childhood Infections and Vaccines of Children’s Healthcare of Atlanta, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA
2Emory Vaccine Center, Emory University, Atlanta, GA, USA
8Yerkes National Primate Research Center, Atlanta, GA, USA
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Meredith E. Davis-Gardner
1Center for Childhood Infections and Vaccines of Children’s Healthcare of Atlanta, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA
2Emory Vaccine Center, Emory University, Atlanta, GA, USA
8Yerkes National Primate Research Center, Atlanta, GA, USA
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Grace Mantus
1Center for Childhood Infections and Vaccines of Children’s Healthcare of Atlanta, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA
2Emory Vaccine Center, Emory University, Atlanta, GA, USA
4Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA
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Lindsay E. Nyhoff
1Center for Childhood Infections and Vaccines of Children’s Healthcare of Atlanta, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA
2Emory Vaccine Center, Emory University, Atlanta, GA, USA
4Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA
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Sarah Bechnak
4Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA
5Hope Clinic of Emory Vaccine Center, Emory University, Decatur, GA, USA
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Ghina Alaaeddine
4Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA
5Hope Clinic of Emory Vaccine Center, Emory University, Decatur, GA, USA
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Amal Naji
4Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA
5Hope Clinic of Emory Vaccine Center, Emory University, Decatur, GA, USA
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Hady Samaha
4Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA
5Hope Clinic of Emory Vaccine Center, Emory University, Decatur, GA, USA
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Matthew Lee
4Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA
5Hope Clinic of Emory Vaccine Center, Emory University, Decatur, GA, USA
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Laurel Bristow
4Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA
5Hope Clinic of Emory Vaccine Center, Emory University, Decatur, GA, USA
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Laila Hussaini
1Center for Childhood Infections and Vaccines of Children’s Healthcare of Atlanta, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA
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Caroline Rose Ciric
1Center for Childhood Infections and Vaccines of Children’s Healthcare of Atlanta, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA
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Phuong-Vi Nguyen
4Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA
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Matthew Gagne
6Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
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Jesmine Roberts-Torres
6Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
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Amy R. Henry
6Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
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Sucheta Godbole
6Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
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Arash Grakoui
2Emory Vaccine Center, Emory University, Atlanta, GA, USA
3Department of Microbiology and Immunology, Emory University, Atlanta, GA, USA
4Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA
8Yerkes National Primate Research Center, Atlanta, GA, USA
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Marybeth Sexton
4Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA
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Anne Piantadosi
4Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA
7Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA
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Jesse J. Waggoner
4Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA
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Daniel C. Douek
6Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
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Evan J. Anderson
1Center for Childhood Infections and Vaccines of Children’s Healthcare of Atlanta, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA
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Nadine Rouphael
4Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA
5Hope Clinic of Emory Vaccine Center, Emory University, Decatur, GA, USA
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Jens Wrammert
1Center for Childhood Infections and Vaccines of Children’s Healthcare of Atlanta, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA
2Emory Vaccine Center, Emory University, Atlanta, GA, USA
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Mehul S. Suthar
1Center for Childhood Infections and Vaccines of Children’s Healthcare of Atlanta, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA
2Emory Vaccine Center, Emory University, Atlanta, GA, USA
3Department of Microbiology and Immunology, Emory University, Atlanta, GA, USA
8Yerkes National Primate Research Center, Atlanta, GA, USA
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  • For correspondence: mehul.s.suthar@emory.edu
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Abstract

The BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) vaccines generate potent neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the global emergence of SARS-CoV-2 variants with mutations in the spike protein, the principal antigenic target of these vaccines, has raised concerns over the neutralizing activity of vaccine-induced antibody responses. The Omicron variant, which emerged in November 2021, consists of over 30 mutations within the spike protein. Here, we used an authentic live virus neutralization assay to examine the neutralizing activity of the SARS-CoV-2 Omicron variant against mRNA vaccine-induced antibody responses. Following the 2nd dose, we observed a 30-fold reduction in neutralizing activity against the omicron variant. Through six months after the 2nd dose, none of the sera from naïve vaccinated subjects showed neutralizing activity against the Omicron variant. In contrast, recovered vaccinated individuals showed a 22-fold reduction with more than half of the subjects retaining neutralizing antibody responses. Following a booster shot (3rd dose), we observed a 14-fold reduction in neutralizing activity against the omicron variant and over 90% of boosted subjects showed neutralizing activity against the omicron variant. These findings show that a 3rd dose is required to provide robust neutralizing antibody responses against the Omicron variant.

Competing Interest Statement

M.S.S serves on the advisory board for Moderna. NR institution receives funding from Pfizer, Quidel, Lilly, Merck and Sanofi Pasteur for research studies. NR serves as a safety consultant for ICON and EMMES.

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.
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Posted December 22, 2021.
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mRNA-1273 and BNT162b2 mRNA vaccines have reduced neutralizing activity against the SARS-CoV-2 Omicron variant
Venkata-Viswanadh Edara, Kelly E. Manning, Madison Ellis, Lilin Lai, Kathryn M. Moore, Stephanie L. Foster, Katharine Floyd, Meredith E. Davis-Gardner, Grace Mantus, Lindsay E. Nyhoff, Sarah Bechnak, Ghina Alaaeddine, Amal Naji, Hady Samaha, Matthew Lee, Laurel Bristow, Laila Hussaini, Caroline Rose Ciric, Phuong-Vi Nguyen, Matthew Gagne, Jesmine Roberts-Torres, Amy R. Henry, Sucheta Godbole, Arash Grakoui, Marybeth Sexton, Anne Piantadosi, Jesse J. Waggoner, Daniel C. Douek, Evan J. Anderson, Nadine Rouphael, Jens Wrammert, Mehul S. Suthar
bioRxiv 2021.12.20.473557; doi: https://doi.org/10.1101/2021.12.20.473557
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mRNA-1273 and BNT162b2 mRNA vaccines have reduced neutralizing activity against the SARS-CoV-2 Omicron variant
Venkata-Viswanadh Edara, Kelly E. Manning, Madison Ellis, Lilin Lai, Kathryn M. Moore, Stephanie L. Foster, Katharine Floyd, Meredith E. Davis-Gardner, Grace Mantus, Lindsay E. Nyhoff, Sarah Bechnak, Ghina Alaaeddine, Amal Naji, Hady Samaha, Matthew Lee, Laurel Bristow, Laila Hussaini, Caroline Rose Ciric, Phuong-Vi Nguyen, Matthew Gagne, Jesmine Roberts-Torres, Amy R. Henry, Sucheta Godbole, Arash Grakoui, Marybeth Sexton, Anne Piantadosi, Jesse J. Waggoner, Daniel C. Douek, Evan J. Anderson, Nadine Rouphael, Jens Wrammert, Mehul S. Suthar
bioRxiv 2021.12.20.473557; doi: https://doi.org/10.1101/2021.12.20.473557

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