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mRNA-1273 efficacy in a severe COVID-19 model: attenuated activation of pulmonary immune cells after challenge

Michelle Meyer, Yuan Wang, Darin Edwards, Gregory R. Smith, Aliza B. Rubenstein, Palaniappan Ramanathan, Chad E. Mire, Colette Pietzsch, Xi Chen, Yongchao Ge, Wan Sze Cheng, Carole Henry, Angela Woods, LingZhi Ma, Guillaume B. E. Stewart-Jones, Kevin W. Bock, Mahnaz Minai, Bianca M. Nagata, Sivakumar Periasamy, Pei-Yong Shi, View ORCID ProfileBarney S. Graham, Ian N. Moore, Irene Ramos, Olga G. Troyanskaya, Elena Zaslavsky, Andrea Carfi, View ORCID ProfileStuart C. Sealfon, Alexander Bukreyev
doi: https://doi.org/10.1101/2021.01.25.428136
Michelle Meyer
1Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555
2Galveston National Laboratory, Galveston, TX 77555
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Yuan Wang
3Department of Computer Science, Princeton University, Princeton NJ 08540
4Lewis-Sigler Institute of Integrative Genomics, Princeton University, Princeton NJ 08540
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Darin Edwards
5Moderna Inc, Cambridge, MA, 02139
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Gregory R. Smith
6Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029
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Aliza B. Rubenstein
6Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029
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Palaniappan Ramanathan
1Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555
2Galveston National Laboratory, Galveston, TX 77555
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Chad E. Mire
2Galveston National Laboratory, Galveston, TX 77555
7Department of Microbiology & Immunology, University of Texas Medical Branch, Galveston, TX 77555
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Colette Pietzsch
1Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555
2Galveston National Laboratory, Galveston, TX 77555
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Xi Chen
4Lewis-Sigler Institute of Integrative Genomics, Princeton University, Princeton NJ 08540
8Center for Computational Biology, Flatiron Institute, Simons Foundation, New York, NY 10010
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Yongchao Ge
6Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029
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Wan Sze Cheng
6Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029
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Carole Henry
5Moderna Inc, Cambridge, MA, 02139
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Angela Woods
5Moderna Inc, Cambridge, MA, 02139
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LingZhi Ma
5Moderna Inc, Cambridge, MA, 02139
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Guillaume B. E. Stewart-Jones
5Moderna Inc, Cambridge, MA, 02139
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Kevin W. Bock
9Infectious Disease Pathogenesis Section, Comparative Medicine Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852
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Mahnaz Minai
9Infectious Disease Pathogenesis Section, Comparative Medicine Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852
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Bianca M. Nagata
9Infectious Disease Pathogenesis Section, Comparative Medicine Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852
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Sivakumar Periasamy
1Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555
2Galveston National Laboratory, Galveston, TX 77555
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Pei-Yong Shi
10Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555
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Barney S. Graham
11Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892
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  • ORCID record for Barney S. Graham
Ian N. Moore
9Infectious Disease Pathogenesis Section, Comparative Medicine Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852
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Irene Ramos
6Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029
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Olga G. Troyanskaya
3Department of Computer Science, Princeton University, Princeton NJ 08540
4Lewis-Sigler Institute of Integrative Genomics, Princeton University, Princeton NJ 08540
8Center for Computational Biology, Flatiron Institute, Simons Foundation, New York, NY 10010
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Elena Zaslavsky
6Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029
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Andrea Carfi
5Moderna Inc, Cambridge, MA, 02139
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  • For correspondence: andrea.carfi@modernatx.com stuart.sealfon@mssm.edu alexander.bukreyev@utmb.edu
Stuart C. Sealfon
6Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029
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  • ORCID record for Stuart C. Sealfon
  • For correspondence: andrea.carfi@modernatx.com stuart.sealfon@mssm.edu alexander.bukreyev@utmb.edu
Alexander Bukreyev
1Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555
2Galveston National Laboratory, Galveston, TX 77555
7Department of Microbiology & Immunology, University of Texas Medical Branch, Galveston, TX 77555
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  • For correspondence: andrea.carfi@modernatx.com stuart.sealfon@mssm.edu alexander.bukreyev@utmb.edu
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ABSTRACT

The mRNA-1273 vaccine was recently determined to be effective against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from interim Phase 3 results. Human studies, however, cannot provide the controlled response to infection and complex immunological insight that are only possible with preclinical studies. Hamsters are the only model that reliably exhibit more severe SARS-CoV-2 disease similar to hospitalized patients, making them pertinent for vaccine evaluation. We demonstrate that prime or prime-boost administration of mRNA-1273 in hamsters elicited robust neutralizing antibodies, ameliorated weight loss, suppressed SARS-CoV-2 replication in the airways, and better protected against disease at the highest prime-boost dose. Unlike in mice and non-human primates, mRNA-1273- mediated immunity was non-sterilizing and coincided with an anamnestic response. Single-cell RNA sequencing of lung tissue permitted high resolution analysis which is not possible in vaccinated humans. mRNA-1273 prevented inflammatory cell infiltration and the reduction of lymphocyte proportions, but enabled antiviral responses conducive to lung homeostasis. Surprisingly, infection triggered transcriptome programs in some types of immune cells from vaccinated hamsters that were shared, albeit attenuated, with mock-vaccinated hamsters. Our results support the use of mRNA-1273 in a two-dose schedule and provides insight into the potential responses within the lungs of vaccinated humans who are exposed to SARS-CoV-2.

Competing Interest Statement

D.E., C.H., A.W., L.M, G.S-J. and A.C. are employees of Moderna, Inc. The other authors declare

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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 January 25, 2021.
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mRNA-1273 efficacy in a severe COVID-19 model: attenuated activation of pulmonary immune cells after challenge
Michelle Meyer, Yuan Wang, Darin Edwards, Gregory R. Smith, Aliza B. Rubenstein, Palaniappan Ramanathan, Chad E. Mire, Colette Pietzsch, Xi Chen, Yongchao Ge, Wan Sze Cheng, Carole Henry, Angela Woods, LingZhi Ma, Guillaume B. E. Stewart-Jones, Kevin W. Bock, Mahnaz Minai, Bianca M. Nagata, Sivakumar Periasamy, Pei-Yong Shi, Barney S. Graham, Ian N. Moore, Irene Ramos, Olga G. Troyanskaya, Elena Zaslavsky, Andrea Carfi, Stuart C. Sealfon, Alexander Bukreyev
bioRxiv 2021.01.25.428136; doi: https://doi.org/10.1101/2021.01.25.428136
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mRNA-1273 efficacy in a severe COVID-19 model: attenuated activation of pulmonary immune cells after challenge
Michelle Meyer, Yuan Wang, Darin Edwards, Gregory R. Smith, Aliza B. Rubenstein, Palaniappan Ramanathan, Chad E. Mire, Colette Pietzsch, Xi Chen, Yongchao Ge, Wan Sze Cheng, Carole Henry, Angela Woods, LingZhi Ma, Guillaume B. E. Stewart-Jones, Kevin W. Bock, Mahnaz Minai, Bianca M. Nagata, Sivakumar Periasamy, Pei-Yong Shi, Barney S. Graham, Ian N. Moore, Irene Ramos, Olga G. Troyanskaya, Elena Zaslavsky, Andrea Carfi, Stuart C. Sealfon, Alexander Bukreyev
bioRxiv 2021.01.25.428136; doi: https://doi.org/10.1101/2021.01.25.428136

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