Abstract

The emergence of 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. High-dose (50 μg) SpFN vaccine, given twice 28 days apart, induced a Th1-biased CD4 T cell helper response and elicited neutralizing antibodies against SARS-CoV-2 wild-type and variants of concern, as well as against SARS-CoV-1. These potent humoral and cell-mediated immune responses translated into rapid elimination of replicating virus in the upper and lower airways and lung parenchyma of nonhuman primates following high-dose SARS-CoV-2 respiratory challenge. The immune response elicited by SpFN vaccination and resulting efficacy in nonhuman primates supports the utility of SpFN as a vaccine candidate for SARS-causing betacoronaviruses.

Highlights

  • The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has reached a milestone with the emergency use authorization, approval, and increasing availability of efficacious vaccines [1]

  • The spike ferritin nanoparticle (SpFN) vaccine was designed as a ferritin-fusion recombinant protein for expression as a nanoparticle, and has been described in detail previously [20]

  • There remains a need for next-generation vaccines that target the broadening antigenic diversity of SARS-CoV-2 and related coronaviruses

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Summary

Introduction

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has reached a milestone with the emergency use authorization, approval, and increasing availability of efficacious vaccines [1]. The accelerating frequency with which variants are emerging raises the specter that host selective pressures may drive the evolution of mutants to escape vaccine-elicited immunity [3]. This concern, coupled with stringent cold-chain requirements for product stability and high unit costs for some vaccine platforms [4], justifies the continued development of cost-effective, thermo-stable vaccines that match currently authorized and approved vaccines in safety and efficacy, and are effective against a wide range of circulating variants and evolving strains, as well as species that may arise from zoonotic reservoirs in the future.

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