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[Preprint]. 2021 Mar 25:2021.03.24.436523. [Version 1] doi: 10.1101/2021.03.24.436523

Efficacy of a Broadly Neutralizing SARS-CoV-2 Ferritin Nanoparticle Vaccine in Nonhuman Primates

Michael G Joyce, Hannah A D King, Ines Elakhal Naouar, Aslaa Ahmed, Kristina K Peachman, Camila Macedo Cincotta, Caroline Subra, Rita E Chen, Paul V Thomas, Wei-Hung Chen, Rajeshwer S Sankhala, Agnes Hajduczki, Elizabeth J Martinez, Caroline E Peterson, William C Chang, Misook Choe, Clayton Smith, Parker J Lee, Jarrett A Headley, Mekdi G Taddese, Hanne A Elyard, Anthony Cook, Alexander Anderson, Kathryn McGuckin-Wuertz, Ming Dong, Isabella Swafford, James B Case, Jeffrey R Currier, Kerri G Lal, Robert J O’Connell, Sebastian Molnar, Manoj S Nair, Vincent Dussupt, Sharon P Daye, Xiankun Zeng, Erica K Barkei, Hilary M Staples, Kendra Alfson, Ricardo Carrion, Shelly J Krebs, Dominic Paquin-Proulx, Nicos Karasavva, Victoria R Polonis, Linda L Jagodzinski, Mihret F Amare, Sandhya Vasan, Paul T Scott, Yaoxing Huang, David D Ho, Natalia de Val, Michael S Diamond, Mark G Lewis, Mangala Rao, Gary R Matyas, Gregory D Gromowski, Sheila A Peel, Nelson L Michael, Diane L Bolton, Kayvon Modjarrad
PMCID: PMC8010721  PMID: 33791694

Abstract

The emergence of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants stresses the continued need for next-generation vaccines that confer broad protection against coronavirus disease 2019 (COVID-19). We developed and evaluated an adjuvanted SARS-CoV-2 Spike Ferritin Nanoparticle (SpFN) vaccine in nonhuman primates (NHPs). High-dose (50 µ g) SpFN vaccine, given twice within a 28 day interval, induced a Th1-biased CD4 T cell helper response and a peak neutralizing antibody geometric mean titer of 52,773 against wild-type virus, with activity against SARS-CoV-1 and minimal decrement against variants of concern. Vaccinated animals mounted an anamnestic response upon high-dose SARS-CoV-2 respiratory challenge that translated into rapid elimination of replicating virus in their upper and lower airways and lung parenchyma. SpFN’s potent and broad immunogenicity profile and resulting efficacy in NHPs supports its utility as a candidate platform for SARS-like betacoronaviruses.

One-Sentence Summary

A SARS-CoV-2 Spike protein ferritin nanoparticle vaccine, co-formulated with a liposomal adjuvant, elicits broad neutralizing antibody responses that exceed those observed for other major vaccines and rapidly protects against respiratory infection and disease in the upper and lower airways and lung tissue of nonhuman primates.

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