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

James Logue, Robert M. Johnson, Nita Patel, Bin Zhou, Sonia Maciejewski, Bryant Foreman, Haixia Zhou, Alyse D. Portnoff, Jing-Hui Tian, Asma Rehman, Marisa E. McGrath, Robert E. Haupt, Stuart M. Weston, Lauren Baracco, Holly Hammond, Mimi Guebre-Xabier, Carly Dillen, M. Madhangi, Ann M. Greene, Michael J. Massare, Greg M. Glenn, Gale Smith and Matthew B. Frieman ()
Additional contact information
James Logue: The University of Maryland School of Medicine
Robert M. Johnson: The University of Maryland School of Medicine
Nita Patel: Novavax, Inc
Bin Zhou: Novavax, Inc
Sonia Maciejewski: Novavax, Inc
Bryant Foreman: Novavax, Inc
Haixia Zhou: Novavax, Inc
Alyse D. Portnoff: Novavax, Inc
Jing-Hui Tian: Novavax, Inc
Asma Rehman: Novavax, Inc
Marisa E. McGrath: The University of Maryland School of Medicine
Robert E. Haupt: The University of Maryland School of Medicine
Stuart M. Weston: The University of Maryland School of Medicine
Lauren Baracco: The University of Maryland School of Medicine
Holly Hammond: The University of Maryland School of Medicine
Mimi Guebre-Xabier: Novavax, Inc
Carly Dillen: The University of Maryland School of Medicine
M. Madhangi: Novavax, Inc
Ann M. Greene: Novavax, Inc
Michael J. Massare: Novavax, Inc
Greg M. Glenn: Novavax, Inc
Gale Smith: Novavax, Inc
Matthew B. Frieman: The University of Maryland School of Medicine

Nature Communications, 2023, vol. 14, issue 1, 1-16

Abstract: Abstract SARS-CoV-2 variants have emerged with elevated transmission and a higher risk of infection for vaccinated individuals. We demonstrate that a recombinant prefusion-stabilized spike (rS) protein vaccine based on Beta/B.1.351 (rS-Beta) produces a robust anamnestic response in baboons against SARS-CoV-2 variants when given as a booster one year after immunization with NVX-CoV2373. Additionally, rS-Beta is highly immunogenic in mice and produces neutralizing antibodies against WA1/2020, Beta/B.1.351, and Omicron/BA.1. Mice vaccinated with two doses of Novavax prototype NVX-CoV2373 (rS-WU1) or rS-Beta alone, in combination, or heterologous prime-boost, are protected from challenge. Virus titer is undetectable in lungs in all vaccinated mice, and Th1-skewed cellular responses are observed. We tested sera from a panel of variant spike protein vaccines and find broad neutralization and inhibition of spike:ACE2 binding from the rS-Beta and rS-Delta vaccines against a variety of variants including Omicron. This study demonstrates that rS-Beta vaccine alone or in combination with rS-WU1 induces antibody-and cell-mediated responses that are protective against challenge with SARS-CoV-2 variants and offers broader neutralizing capacity than a rS-WU1 prime/boost regimen alone. Together, these nonhuman primate and murine data suggest a Beta variant booster dose could elicit a broad immune response to fight new and future SARS-CoV-2 variants.

Date: 2023
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DOI: 10.1038/s41467-022-35606-6

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