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

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 glycoprotein of SARS-CoV-2 fused to a human IgG1 Fc domain. CoV-RBD121-NP elicits strong antibody responses in C57BL/6 mice and is...

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Bibliographic Details
Published in:Vaccines (Basel) 2021-11, Vol.9 (11), p.1346
Main Authors: DeMarco, Jennifer K, Royal, Joshua M, Severson, William E, Gabbard, Jon D, Hume, Steve, Morton, Josh, Swope, Kelsi, Simpson, Carrie A, Shepherd, John W, Bratcher, Barry, Palmer, Kenneth E, Pogue, Gregory P
Format: Article
Language:English
Subjects:
Antibodies
Antibody response
betacoronaviridae
betacoronavirus
Coronaviruses
COVID-19
Cytokines
Domains
Glycoproteins
Immunization
Immunoglobulin G
Inflammation
Middle East respiratory syndrome
Mortality
Nanoparticles
Neutralizing
Plant virus diseases
SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2
Spike glycoprotein
TMV
Tobacco
vaccine
Vaccines
Viral diseases
Viruses
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Summary: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 glycoprotein 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 characteristic of severe cases of COVID-19.
ISSN:2076-393X
2076-393X
DOI:10.3390/vaccines9111346