A central tenet in the design of vaccines is the display of native-like antigens in the elicitation of protective immunity. The abundance of N-linked glycans across the SARS-CoV-2 spike protein is a potential source of heterogeneity among the many different vaccine candidates under investigation. Here, we investigate the glycosylation of recombinant SARS-CoV-2 spike proteins from five different laboratories and compare them against S protein from infectious virus, cultured in Vero cells. We find patterns that are conserved across all samples, and this can be associated with site-specific stalling of glycan maturation that acts as a highly sensitive reporter of protein structure. Molecular dynamics simulations of a fully glycosylated spike support a model of steric restrictions that shape enzymatic processing of the glycans. These results suggest that recombinant spike-based SARS-CoV-2 immunogen glycosylation reproducibly recapitulates signatures of viral glycosylation.
Journal article
Biochemistry
02/07/2021
60
2153 - 2169
School of Biological Sciences, University of Southampton, Southampton SO17 1BJ, U.K.
Vero Cells, Animals, Humans, Protein Conformation, Protein Binding, Glycosylation, Molecular Dynamics Simulation, Spike Glycoprotein, Coronavirus, Chlorocebus aethiops, COVID-19, SARS-CoV-2, COVID-19 Vaccines