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

Jennifer K DeMarco; Joshua M Royal; William E Severson; Jon D Gabbard; Steve Hume; Josh Morton; Kelsi Swope; Carrie A Simpson; John W Shepherd; Barry Bratcher; Kenneth E Palmer; Gregory P Pogue

doi:10.3390/vaccines9111346

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

Vaccines (Basel). 2021 Nov 17;9(11):1346. doi: 10.3390/vaccines9111346.

Authors

Jennifer K DeMarco^{1

2}, Joshua M Royal³, William E Severson¹, Jon D Gabbard¹, Steve Hume³, Josh Morton³, Kelsi Swope³, Carrie A Simpson³, John W Shepherd³, Barry Bratcher³, Kenneth E Palmer^{1

4

5}, Gregory P Pogue^{3

6}

Affiliations

¹ Center for Predictive Medicine for Biodefense and Emerging Infectious Diseases, University of Louisville, Louisville, KY 40202, USA.
² Department of Microbiology and Immunology, University of Louisville, Louisville, KY 40202, USA.
³ Kentucky BioProcessing, Inc., Owensboro, KY 42301, USA.
⁴ James Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA.
⁵ Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40202, USA.
⁶ IC² Institute, University of Texas at Austin, Austin, TX 78805, USA.

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 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.

Keywords: COVID-19; SARS-CoV-2; TMV; betacoronaviridae; betacoronavirus; vaccine.