MIT: A new technology to detect neutralizing antibodies to the course of COVID-19

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MIT: A new technology to detect neutralizing antibodies to the course of COVID-19

MIT: A new technology to detect neutralizing antibodies to the course of COVID-19.

A new technique developed by MIT chemists can be used to detect neutralizing antibodies to the course of COVID-19.

Scientists at MIT have developed a new technique that uses lectin displacement to detect neutralizing antibodies against viruses such as SARS-CoV-2, providing a potential way to assess vaccine effectiveness and against viral variants. method of protection. They have applied for a patent for this technology.

Antibodies that can disarm the virus are called neutralizing antibodies and are key to the body’s ability to fight infection. MIT chemists have come up with a new way to identify these neutralizing antibodies in blood samples by analyzing how the antibodies interact with sugar molecules on the surface of viral proteins.

The new test may help reveal whether someone has neutralizing antibodies against viruses such as SARS-CoV-2, the virus researchers focused on in their studies. Neutralizing antibodies, which can be produced through vaccination or previous infection, can provide protection against future infection.

“This type of assay could be used to check whether a patient is actually protected by a vaccine,” said Laura Kiessling, a Novartis professor of chemistry at MIT and the paper’s senior author. “If someone is at high risk, it would be really beneficial to be able to quickly determine whether they have neutralizing antibodies.”

Using common equipment already found in many biochemistry labs, the technique could also help researchers determine how well current vaccines protect against newer variants of SARS-CoV-2, Kiessling said.

Former MIT postdoc Michael Wuo and MIT research scientist Amanda Dugan are the lead authors of the paper, which appears May 10 in the open-access journal ACS Central Science.

To neutralize or not to neutralize?

Most SARS-CoV-2 vaccines target the virus’s spike protein, which the virus uses to enter host cells through the ACE2 receptor. Like most proteins found on the viral envelope, the spike protein is surrounded by a large number of sugar chains hanging from the protein.

Kiessling, whose lab studies how proteins interact with carbohydrates on the surface of cells, wondered if it would be possible to create a “fingerprint” of different antibodies based on how they interacted with sugar molecules on viral proteins like SARS. CoV-2 spike protein.

“To tell if an antibody is neutralizing, you typically have to do a relatively difficult set of assays,” Kiessling said. “You have to test whether the antibody prevents the virus from infecting cells. We thought that if we could develop that fingerprint, then we could Faster identification of neutralizing antibodies.”

To this end, the researchers created a group of commercially available lectins (proteins that bind to carbohydrates) obtained from a variety of organisms, mainly plants and bacteria. Lectins, which are often involved in functions such as cell-cell interactions and immune responses, bind to sugar molecules at the ends of sugar chains when they hang from proteins.

When the researchers exposed the SARS-CoV-2 spike protein to these lectins, each lectin attached to a specific subset of sugar molecules found on the protein. The researchers then added serum containing antibodies against SARS-CoV-2. If the antibodies have high affinity for the spike protein, they push away the lectin that is already present.

Each antibody displaces a different set of lectins, depending on its binding specificity, and this displacement can be measured using a laboratory test called an enzyme-linked lectin assay (ELLA).

By analyzing whether each antibody displaces 28 different lectins that bind to the spike protein, the researchers were able to identify patterns of lectin displacement that create a unique “fingerprint” for each antibody.

The researchers first determined the fingerprints of known neutralizing or non-neutralizing antibodies. They then tested blood samples from the patients and determined whether the antibodies in those samples were neutralizing by comparing them to the fingerprints produced by known neutralizing antibodies.

“By looking at the different patterns, we could see that the neutralizing antibodies belonged to a different class than the non-neutralizing antibodies,” Kiessling said.

Antibody profile

Using this analysis, the researchers were also able to sort the antibodies according to whether they came from people who received the Moderna COVID-19 vaccine or the Pfizer COVID-19 vaccine, each of which targets a slightly different sequence of viral RNA.

The researchers have applied for a patent for the technology, which they hope can be developed as a rapid test in a doctor’s office to determine an individual patient’s antibody profile.

The technique could potentially be used to identify neutralizing antibodies against new variants of SARS-CoV-2 or other disease-causing viruses, Kiessling said. Now that the researchers had a panel of lectins to test for, they just had to rerun the analysis with antibodies known to be neutralizing and non-neutralizing so they could determine the correct fingerprint for those antibodies.

“We can use the same set of lectins for all SARS-CoV-2 variants of interest,” Kiessling said. “It’s useful for any new viruses that come out, as long as they have a viral envelope.”

MIT: A new technology to detect neutralizing antibodies to the course of COVID-19

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Tags: COVID-19