February 28, 2023

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

NIS Mountain Hero

Cryo-TEM imaging can be a powerful tool for determining the structure of antibody antigen complexes, such as those in SARS-CoV-2 Beta B.1.351.

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.

Citation

Logue, J., Johnson, R.M., Patel, N. et al. Immunogenicity and protection of a variant nanoparticle vaccine that confers broad neutralization against SARS-CoV-2 variants. Nat Commun14, 1130 (2023). https://doi.org/10.1038/s41467-022-35606-6

Authors
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 & Matthew B. Frieman
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