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Boosting with Omicron-matched or historical mRNA vaccines increases neutralizing antibody responses and protection against B.1.1.529 infection in mice

Baoling Ying, Suzanne M. Scheaffer, Bradley Whitener, Chieh-Yu Liang, Oleksandr Dmytrenko, Samantha Mackin, Kai Wu, Diana Lee, Laura E. Avena, Zhenlu Chong, James Brett Case, LingZhi Ma, Thu Kim, Caralyn Sein, Angela Woods, Daniela Montes Berrueta, Andrea Carfi, Sayda M. Elbashir, Darin K. Edwards, Larissa B. Thackray, View ORCID ProfileMichael S. Diamond
doi: https://doi.org/10.1101/2022.02.07.479419
Baoling Ying
1Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
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Suzanne M. Scheaffer
1Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
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Bradley Whitener
1Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
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Chieh-Yu Liang
1Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
2Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, USA
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Oleksandr Dmytrenko
1Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
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Samantha Mackin
1Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
2Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, USA
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Kai Wu
3Moderna, Inc., Cambridge MA, USA
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Diana Lee
3Moderna, Inc., Cambridge MA, USA
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Laura E. Avena
3Moderna, Inc., Cambridge MA, USA
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Zhenlu Chong
1Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
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James Brett Case
1Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
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LingZhi Ma
3Moderna, Inc., Cambridge MA, USA
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Thu Kim
3Moderna, Inc., Cambridge MA, USA
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Caralyn Sein
3Moderna, Inc., Cambridge MA, USA
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Angela Woods
3Moderna, Inc., Cambridge MA, USA
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Daniela Montes Berrueta
3Moderna, Inc., Cambridge MA, USA
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Andrea Carfi
3Moderna, Inc., Cambridge MA, USA
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Sayda M. Elbashir
3Moderna, Inc., Cambridge MA, USA
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Darin K. Edwards
3Moderna, Inc., Cambridge MA, USA
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Larissa B. Thackray
1Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
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  • For correspondence: lthackray@wustl.edu diamond@wusm.wustl.edu
Michael S. Diamond
1Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
2Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, USA
4Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA
5The Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine. St. Louis, MO, USA
6Center for Vaccines and Immunity to Microbial Pathogens, Washington University School of Medicine, Saint Louis, MO, USA
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  • ORCID record for Michael S. Diamond
  • For correspondence: lthackray@wustl.edu diamond@wusm.wustl.edu
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ABSTRACT

The B.1.1.529 Omicron variant jeopardizes vaccines designed with early pandemic spike antigens. Here, we evaluated in mice the protective activity of the Moderna mRNA-1273 vaccine against B.1.1.529 before or after boosting with preclinical mRNA-1273 or mRNA-1273.529, an Omicron-matched vaccine. Whereas two doses of mRNA-1273 vaccine induced high levels of serum neutralizing antibodies against historical WA1/2020 strains, levels were lower against B.1.1.529 and associated with infection and inflammation in the lung. A primary vaccination series with mRNA-1273.529 potently neutralized B.1.1.529 but showed limited inhibition of historical or other SARS-CoV-2 variants. However, boosting with mRNA-1273 or mRNA-1273.529 vaccines increased serum neutralizing titers and protection against B.1.1.529 infection. Nonetheless, the levels of inhibitory antibodies were higher, and viral burden and cytokines in the lung were slightly lower in mice given the Omicron-matched mRNA booster. Thus, in mice, boosting with mRNA-1273 or mRNA-1273.529 enhances protection against B.1.1.529 infection with limited differences in efficacy measured.

Competing Interest Statement

M.S.D. is a consultant for Inbios, Vir Biotechnology, Senda Biosciences, and Carnival Corporation, and on the Scientific Advisory Boards of Moderna and Immunome. The Diamond laboratory has received unrelated funding support in sponsored research agreements from Vir Biotechnology, Kaleido, and Emergent BioSolutions and past support from Moderna not related to these studies. K.W., D.L., L.E.A., L.M., C.H., A.W., A.C., S.E. and D.K.E. are employees of and shareholders in Moderna Inc.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted February 09, 2022.
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Boosting with Omicron-matched or historical mRNA vaccines increases neutralizing antibody responses and protection against B.1.1.529 infection in mice
Baoling Ying, Suzanne M. Scheaffer, Bradley Whitener, Chieh-Yu Liang, Oleksandr Dmytrenko, Samantha Mackin, Kai Wu, Diana Lee, Laura E. Avena, Zhenlu Chong, James Brett Case, LingZhi Ma, Thu Kim, Caralyn Sein, Angela Woods, Daniela Montes Berrueta, Andrea Carfi, Sayda M. Elbashir, Darin K. Edwards, Larissa B. Thackray, Michael S. Diamond
bioRxiv 2022.02.07.479419; doi: https://doi.org/10.1101/2022.02.07.479419
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Boosting with Omicron-matched or historical mRNA vaccines increases neutralizing antibody responses and protection against B.1.1.529 infection in mice
Baoling Ying, Suzanne M. Scheaffer, Bradley Whitener, Chieh-Yu Liang, Oleksandr Dmytrenko, Samantha Mackin, Kai Wu, Diana Lee, Laura E. Avena, Zhenlu Chong, James Brett Case, LingZhi Ma, Thu Kim, Caralyn Sein, Angela Woods, Daniela Montes Berrueta, Andrea Carfi, Sayda M. Elbashir, Darin K. Edwards, Larissa B. Thackray, Michael S. Diamond
bioRxiv 2022.02.07.479419; doi: https://doi.org/10.1101/2022.02.07.479419

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