Site-specific Glycan Analysis of the SARS-CoV-2 Spike
May 04, 2020
Volume and Number
2020;eabb9983. doi: 10.1126/science.abb9983. Online ahead of print. 2020 May 4.
Watanabe Y, Allen JD, Wrapp D, McLellan JS, Crispin M
The emergence of the betacoronavirus, SARS-CoV-2, the causative agent of COVID-19, represents a significant threat to global human health. Vaccine development is focused on the principal target of the humoral immune response, the spike (S) glycoprotein, which mediates cell entry and membrane fusion.
SARS-CoV-2 S gene encodes 22 N-linked glycan sequons per protomer, which likely play a role in protein folding and immune evasion. Here, using a site-specific mass spectrometric approach, we reveal the glycan structures on a recombinant SARS-CoV-2 S immunogen. This analysis enables mapping of the glycan-processing states across the trimeric viral spike.
We show how SARS-CoV-2 S glycans differ from typical host glycan processing, which may have implications in viral pathobiology and vaccine design.
- SARS-CoV-2 S protein is less densely glycosylated and that the glycans form less of a shield compared with other viral glycoproteins including HIV-1 Env and LASV GPC, which may be beneficial for the elicitation of neutralizing antibodies.
- While small mannose-type clusters have been characterized on the S1 subunit of Middle East respiratory syndrome (MERS) CoV S, no such phenomenon has been observed for SARS-CoV-1 or SARS-CoV-2 S proteins.
- Our glycosylation analysis of SARS-CoV-2 offers a detailed benchmark of site-specific glycan signatures characteristic of a natively folded trimeric spike.
- As an increasing number of glycoprotein-based vaccine candidates are being developed, their detailed glycan analysis offers a route for comparing immunogen integrity and will also be important to monitor as manufacturing processes are scaled for clinical use.
- Glycan profiling will therefore also be an important measure of antigen quality in the manufacture of serological testing kits.
- Finally, with the advent of nucleotide-based vaccines, it will be important to understand how those delivery mechanisms impact immunogen processing and presentation.