ABSTRACT
Viral outbreaks do occur regularly but the severity of outcome may vary. Genetic reassortment gives rise to novel viral strains causing new outbreaks with epidemic or pandemic potential against which mankind is not prepared to fight. The early 21st century has witnessed pandemics like severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV) and SARS-CoV-2, and novel influenzas (avian and swine), originating from specific geographical regions and transmitting across the globe causing heavy damages in all sectors. Here, in this chapter we focus mainly on SARS-CoV with reference to other similar respiratory infections like MERS-CoV and SARS-CoV-2. The lessons learned so far in the early 21st century are discussed with emphasis on future directions. © 2021 Elsevier Inc. All rights reserved.
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.