October 2, 2022

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How does Spike protein glycosylation affect the efficacy of COVID-19 vaccine?

How does Spike protein glycosylation affect the efficacy of COVID-19 vaccine?



 

How does Spike protein glycosylation affect the efficacy of COVID-19 vaccine?

 

The new coronavirus spike protein contains 22 N glycosylation sites and 2 O glycosylation sites, and the glycosylation of these sites can hinder epitope recognition.

Spike protein glycosylation is affected by cell expression lines. In vivo, spike protein usually has complex, heterozygous, and high mannose glycosylation modifications, while in HEK293 and other cell lines, it is modified with high mannose type.

Mainly, this change reduces the ability of the virus to invade cells.

However, the role of glycosylation in the spike protein-mediated viral infection has not been elucidated.

 

The study ” Vaccination with SARS-CoV-2 spike protein lacking glycan shields elicits enhanced protective responses in animal models ” published in Science Translational Medicine provides more details for understanding the role of spike protein glycosylation and vaccine design.

 

How does Spike protein glycosylation affect the efficacy of COVID-19 vaccine?

 

The researchers expressed the COVID-19 spike protein in primary lung epithelial cells, and the results showed that the sialylation modification is essential for the high affinity of the spike protein to the receptor, and high mannose or single N-acetylglucosamine modification can lead to the affinity. weaken.

Moreover, the ability of pseudovirus to infect cells was also weakened after mutation of N-glycosylation or O-glycosylation sites, especially the mutation of N801 and N1194 caused the virus to lose its ability to infect.

Comparing the glycosylation profiles of spike proteins expressed by lung epithelial cells and HEK293T cells, the researchers found that complex glycosylation and sialylation were more abundant in the spike proteins expressed in lung epithelial cells.

 

How does Spike protein glycosylation affect the efficacy of COVID-19 vaccine?

 

By comparing the sequence and structure of the spike protein, the researchers found that conserved sites often contain conserved glycosylation sites, such as the flanking of the RBD region, the S2 stem region, the S2 C-terminus, and the HR2 region. 20-40% of these regions are covered by glycan shielding.

 

How does Spike protein glycosylation affect the efficacy of COVID-19 vaccine?

 

So what effect do these glycosylation modifications have on inducing an immune response?

The researchers constructed three spike proteins: hypermannosylated (SHM), single N -acetylglucosamine modified ( SMG ), and fully glycosylated ( SFG ), which were used as vaccines to immunize mice with two injections. , the results showed that SMG induced immune response better than the other two groups, with 3.6 times higher antibody neutralization efficacy, and at the same time induced more IL-21 follicular helper T cells, granzyme CD8 T cells, and more Th1/Th2 immune responses. for equilibrium.

After the third boost, the mice produced more Spike -specific B cells, and SMG induced a different type of antibody than SFG . The enzyme-linked immunosorbent assay showed that SMG had high neutralizing activity against different 2019- nCoV variants (Omicron was not tested), but the endpoint titer was not significantly different from the SFG group .

 

How does Spike protein glycosylation affect the efficacy of COVID-19 vaccine?

 

In order to further evaluate the protective efficacy of the SMG vaccine in vivo, the researchers used ferrets and hACE2 mice as models respectively, and found that the SMG treatment group had significantly lighter symptoms and a higher survival rate. % protected mice.

 

 

The researchers isolated spike protein-specific B cells from SMG -treated mice and identified a monoclonal antibody, m31A7, that was present only in SMG – treated mice .

The antibody can inhibit various pseudoviruses at the picomolar level, and the inhibitory effect is 1000 times that of the EY6A antibody.

Cryo-EM structural analysis indicated that m31A7 was able to bind to the RBD conformation in the up-state and avoided the mutation sites of most mutants.

 

 

 

 

How does Spike protein glycosylation affect the efficacy of COVID-19 vaccine?

(source:internet, reference only)


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