Oxford-AstraZeneca COVID vaccine causes SARS-CoV-2-like cell surges

Scientists from the University of Oxford and the University of Southampton report in the journal ACS Central Science that cells infected with the ChAdOx1 vaccine produce cellular proteins on cells similar to those produced by natural SARS-CoV-2 infection.

Artistic painting of a protein jump on the surface of cells exposed to vaccines. Credit for the painting: University of Southampton

The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which emerges from the envelope of the virus, is a key structure responsible for infecting host cells. The S1 subunit helps bind the virus to the enzyme that converts angiotensin 2 (ACE2), and the S2 subunit helps fuse the membrane with the host cell.

Viral spike protein is the main target of vaccines, but vaccines use different methods to target spike protein. The Moderna and Pfizer vaccines encode full-length spike protein with two mutations for stability. The nephew’s vaccine uses an inactivated virus that is a wild-type class of protein.

The goal of most vaccines is to elicit a strong immune response, mainly against the receptor-binding domain (RBD) of class proteins that has several neutralizing epitopes. To enable this, many vaccines include mutations that ensure that the spike protein is in conformation before it fuses with the host cell.

The AstraZeneca ChAdOx1 vaccine uses chimpanzee adenovirus and encodes full-length protein classes. It has been shown to elicit a strong immune response as well as a T-cell response. In a recent study, researchers report the characteristics of vaccine-expressed class proteins.

A graph showing how protein spikes form on the surface of cells represented by the vaccine.  Credit for the painting: University of Southampton

A graph showing how protein spikes form on the surface of cells represented by the vaccine. Credit for the painting: University of Southampton

Characterizing spike protein produced by vaccination

The researchers used HeLa S3 cells infected with the ChAdOx1 vaccine to detect the presence of class proteins on the cell surface. Vaccinated serum mice have shown that about 60-70% of cells express protein class.

The way in which the spike protein is processed after vaccination depends on both the receptors and the enzymes produced by the spike-producing cells. The presence of receptors such as ACE2, mainly in the nose, gastrointestinal tract, and lungs, may result in altered protein class structure.

However, these receptors are generally not present in the cell types targeted by the ChAdOx1 vaccine, which is given intramuscularly. Cells selected for this study also do not express these receptors and may act as a suitable replacement for in vitro studies.

Testing using recombinant enzyme for the conversion of angiotensin 2 (ACE2) and human monoclonal antibodies confirmed that the protein class is present in the correct conformation, just as it is in the wild-type virus.

The team then used cryo-electron tomography on vaccine-infected cells to understand the structure of the spikes on the cells. They saw that the cell surface was covered with protrusions, similar to the ear protein on SARS-CoV-2. Further analysis of the image of the protrusions revealed that their structure was very similar to the conformation of the spike proteins before membrane fusion.

The presence of class protein in vaccinated cells provides good evidence that the vaccine can generate a strong immune response. Unlike some other vaccines, the ChAdOx1 vaccine does not use any mutations in the protein class to ensure its stability.

The produced protein class mimics a natural infection

The spike virus protein also has glycans, a type of sugar, that cover it, masking the virus so that the host’s immune response does not detect the virus. This is a common strategy that many viruses use to avoid the host’s immune system. Thus, it is crucial that the proteins of the classes produced by vaccination also produce these glycans in order to ensure complete imitation of the virus for the production of suitable neutralizing antibodies.

The average cryoET and subtomogram for ChAdOx1 nCoV-19 performed.  (A) Tomographic section of U2OS cell transduced with ChAdOx1 nCoV-19.  The slice is 6.4 Å thick;  PM = plasma membrane, scale scale = 100 nm.  (B) Detailed view of the boxed area indicated in (A).  The white tips of the arrows indicate the proteins of the spikes on the cell surface;  scale = 50 nm.  (C - E) Average of the subtomogram of ChAdOx1 nCoV-19 spikes at a resolution of 11.6 Å, as shown by the Fourier-Shell correlation at 0.5 limit values ​​(C), shown from the side view (D) and the top view (E) .  The SARS-CoV-2 (PDB 6ZB5) atomic model (29) was incorporated for reference.

The average cryoET and subtomogram for ChAdOx1 nCoV-19 performed. (A) Tomographic section of U2OS cell transduced with ChAdOx1 nCoV-19. The slice is 6.4 Å thick; PM = plasma membrane, scale scale = 100 nm. (B) Detailed view of the boxed area indicated in (A). The white tips of the arrows indicate the proteins of the spikes on the cell surface; scale = 50 nm. (C – E) Average of the subtomogram of ChAdOx1 nCoV-19 spikes at a resolution of 11.6 Å, as shown by the Fourier-Shell correlation at 0.5 limit values ​​(C), shown from the side view (D) and the top view (E) . The SARS-CoV-2 atomic model (PDB 6ZB5) (29) was incorporated for reference.

To test for the presence of glycans, the team used vaccine-infected HEK293 cells and used enzymes to generate glycopeptides. Tests revealed high levels of glycans present on the spike, providing evidence that the class proteins produced by ChAdOx1 vaccination are similar to the class class expressed by natural infection, triggering an immune response that can protect against COVID-19.

The team used cryo-electron microscopy to further study glycosylation. They found that glycosylation was a mixture of oligomanosis / hybrid sites and a complex type. However, they did not detect O-linked glycans, perhaps due to their low prevalence.

Thus, the results reveal that ChAdOx1 vaccination produces a protein class that is very similar to that produced by the SARS-CoV-2 virus after natural infection, providing more evidence that the vaccine activates the immune system in the fight against COVID-19.

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