Cov‐rbd121‐np vaccine candidate protects against symptomatic disease following sars‐cov‐2 challenge in k18‐hace2 mice and induces protective responses that prevent covid‐19‐associated immunopathology

Abstract

We developed a SARS‐CoV‐2 vaccine candidate (CoV‐RBD121‐NP) comprised of a tobacco mosaic virus‐like nanoparticle conjugated to the receptor‐binding domain of the spike glyco-protein of SARS‐CoV‐2 fused to a human IgG1 Fc domain. CoV‐RBD121‐NP elicits strong antibody responses in C57BL/6 mice and is stable for up to 12 months at 2–8 or 22–28 °C. Here, we showed that this vaccine induces a strong neutralizing antibody response in K18‐hACE2 mice. Furthermore, we demonstrated that immunization protects mice from virus‐associated mortality and symptomatic disease. Our data indicated that a sufficient pre‐existing pool of neutralizing antibodies is required to restrict SARS‐CoV‐2 replication upon exposure and prevent induction of inflammatory mediators associated with severe disease. Finally, we identified a potential role for CXCL5 as a protective cytokine in SARS‐CoV‐2 infection. Our results suggested that disruption of the CXCL5 and CXCL1/2 axis may be important early components of the inflammatory dysregulation that is char-acteristic of severe cases of COVID‐19.