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Immunogenicity and In vivo protection of a variant nanoparticle vaccine that confers broad protection against emerging SARS-CoV-2 variants

James Logue, Robert Johnson, Nita Patel, Bin Zhou, Sonia Maciejewski, Haixia Zhou, Alyse Portnoff, Jing-Hui Tian, Marisa McGrath, Robert Haupt, Stuart Weston, Holly Hammond, Mimi Guebre-Xabier, Carly Dillen, Joyce Plested, Shane Cloney-Clark, Ann M Greene, Mike Massare, Greg Glenn, Gale Smith, Matthew Frieman
doi: https://doi.org/10.1101/2021.06.08.447631
James Logue
1The Department of Microbiology and Immunology, The University of Maryland School of Medicine, Baltimore, MD, 21201
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Robert Johnson
1The Department of Microbiology and Immunology, The University of Maryland School of Medicine, Baltimore, MD, 21201
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Nita Patel
2Novavax, Inc. 21 Firstfield Road, Gaithersburg, MD 20878
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Bin Zhou
2Novavax, Inc. 21 Firstfield Road, Gaithersburg, MD 20878
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Sonia Maciejewski
2Novavax, Inc. 21 Firstfield Road, Gaithersburg, MD 20878
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Haixia Zhou
2Novavax, Inc. 21 Firstfield Road, Gaithersburg, MD 20878
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Alyse Portnoff
2Novavax, Inc. 21 Firstfield Road, Gaithersburg, MD 20878
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Jing-Hui Tian
2Novavax, Inc. 21 Firstfield Road, Gaithersburg, MD 20878
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Marisa McGrath
1The Department of Microbiology and Immunology, The University of Maryland School of Medicine, Baltimore, MD, 21201
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Robert Haupt
1The Department of Microbiology and Immunology, The University of Maryland School of Medicine, Baltimore, MD, 21201
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Stuart Weston
1The Department of Microbiology and Immunology, The University of Maryland School of Medicine, Baltimore, MD, 21201
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Holly Hammond
1The Department of Microbiology and Immunology, The University of Maryland School of Medicine, Baltimore, MD, 21201
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Mimi Guebre-Xabier
2Novavax, Inc. 21 Firstfield Road, Gaithersburg, MD 20878
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Carly Dillen
1The Department of Microbiology and Immunology, The University of Maryland School of Medicine, Baltimore, MD, 21201
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Joyce Plested
2Novavax, Inc. 21 Firstfield Road, Gaithersburg, MD 20878
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Shane Cloney-Clark
2Novavax, Inc. 21 Firstfield Road, Gaithersburg, MD 20878
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Ann M Greene
2Novavax, Inc. 21 Firstfield Road, Gaithersburg, MD 20878
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Mike Massare
2Novavax, Inc. 21 Firstfield Road, Gaithersburg, MD 20878
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Greg Glenn
2Novavax, Inc. 21 Firstfield Road, Gaithersburg, MD 20878
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Gale Smith
2Novavax, Inc. 21 Firstfield Road, Gaithersburg, MD 20878
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Matthew Frieman
1The Department of Microbiology and Immunology, The University of Maryland School of Medicine, Baltimore, MD, 21201
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  • For correspondence: mfrieman@som.umaryland.edu
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Abstract

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) continues to spread globally. As SARS-CoV-2 has transmitted from person to person, variant viruses have emerged with elevated transmission rates and higher risk of infection for vaccinees. We present data showing that a recombinant prefusion-stabilized Spike (rS) protein based on the B.1.351 sequence (rS-B.1.351) was highly immunogenic in mice and produced neutralizing antibodies against SARS-CoV-2/WA1, B.1.1.7, and B.1.351. Mice vaccinated with our prototype vaccine NVX-CoV2373 (rS-WU1) or rS-B.1.351 alone, in combination, or as a heterologous prime boost, were protected when challenged with live SARS-CoV-2/B.1.1.7 or SARS-CoV-2/B.1.351. Virus titer was reduced to undetectable levels in the lungs post-challenge in all vaccinated mice, and Th1-skewed cellular responses were observed. A strong anamnestic response was demonstrated in baboons boosted with rS-B.1.351 approximately one year after immunization with NVX-CoV2373 (rS-WU1). An rS-B.1.351 vaccine alone or in combination with prototype rS-WU1 induced protective antibody- and cell-mediated responses that were protective against challenge with SARS-CoV-2 variant viruses.

Competing Interest Statement

Authors are either employees of Novavax or have been supported by funding from Novavax at UMSOM.

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-ND 4.0 International license.
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Posted June 09, 2021.
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Immunogenicity and In vivo protection of a variant nanoparticle vaccine that confers broad protection against emerging SARS-CoV-2 variants
James Logue, Robert Johnson, Nita Patel, Bin Zhou, Sonia Maciejewski, Haixia Zhou, Alyse Portnoff, Jing-Hui Tian, Marisa McGrath, Robert Haupt, Stuart Weston, Holly Hammond, Mimi Guebre-Xabier, Carly Dillen, Joyce Plested, Shane Cloney-Clark, Ann M Greene, Mike Massare, Greg Glenn, Gale Smith, Matthew Frieman
bioRxiv 2021.06.08.447631; doi: https://doi.org/10.1101/2021.06.08.447631
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Immunogenicity and In vivo protection of a variant nanoparticle vaccine that confers broad protection against emerging SARS-CoV-2 variants
James Logue, Robert Johnson, Nita Patel, Bin Zhou, Sonia Maciejewski, Haixia Zhou, Alyse Portnoff, Jing-Hui Tian, Marisa McGrath, Robert Haupt, Stuart Weston, Holly Hammond, Mimi Guebre-Xabier, Carly Dillen, Joyce Plested, Shane Cloney-Clark, Ann M Greene, Mike Massare, Greg Glenn, Gale Smith, Matthew Frieman
bioRxiv 2021.06.08.447631; doi: https://doi.org/10.1101/2021.06.08.447631

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