Abstract
SARS-CoV-2 surface spike protein mediates the viral entry into the host cell and represents the primary immunological target of COVID-19 vaccines as well as post-exposure immunotherapy. Establishment of the highly immunogenic B-cell epitope profile of SARS-CoV-2 proteins in general, and that of the spike protein in particular, may contribute to the development of sensitive diagnostic tools and identification of vaccine` candidate targets. In the current study, the anti-viral antibody response in transgenic K18-hACE-2 mice was examined by implementing an immunodominant epitope mapping approach of the SARS-CoV-2 spike. Serum samples for probing an epitope array covering the entire spike protein were collected from mice following infection with the original SARS-CoV-2 strain as well as the B.1.1.7 Alpha and B.1.351 Beta genetic variants of concern. The analysis resulted in distinction of six linear epitopes common to the humoral response against all virus variants inspected at a frequency of more than 20% of the serum samples. Finally, the universality of the response was probed by cross-protective in vitro experiments using plaque-reducing neutralization tests. The data presented here has important implications for prediction of the efficacy of immune countermeasures against emerging SARS-CoV-2 variants.
Highlights
Since the onset of the current coronavirus pandemic, limiting the dissemination of SARS-CoV-2, the etiological agent of the COVID-19, represents an objective of utmost public health priority
SARS-CoV-2 VOCs accumulated mutations throughout their genomes, the mutations that map to the spike glycoprotein attract most of the scientific attention, due to the central role that the spike has in the viral pathogenesis and considering that the spike represents the antigen targeted by all FDA-approved vaccines against COVID-19
The array was probed with sera samples collected from K18-hACE2 transgenic mice surviving from an infection with either the BavPat1/2020SARS-CoV-2 isolate (Ref-SKU: 026V-03883; WT) and the two variants of concern (VOCs): B.1.1.7 Alpha and
Summary
Since the onset of the current coronavirus pandemic, limiting the dissemination of SARS-CoV-2, the etiological agent of the COVID-19, represents an objective of utmost public health priority. Accumulating structural, biochemical and immunological data revealed that the NTD and to a lesser extent the RBD of the VOCs underwent significant conformational changes that lowered the efficacy of antibodies directed against these regions of the spike glycoprotein [14,15]. These observations may affect the efficacy of the FDA-approved vaccines, as all of them were generated against the Wuhan Hu-1 initial isolate spike glycoprotein [16]
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