MIT chemists have developed a novel method to detect neutralizing antibodies in a blood sample, which are crucial in fighting infections. By examining how antibodies interact with sugar molecules present on the surface of a viral protein, the scientists can identify these antibodies. The study primarily focuses on SARS-CoV-2, but the test can be used to determine the presence of neutralizing antibodies against other viruses as well. This new assay has the potential to confirm vaccine efficacy or detect those at high risk of infection.
The technique can also aid researchers in evaluating the effectiveness of current vaccines against emerging variants of the virus. The study, authored by Michael Wuo and Amanda Dugan, is published in ACS Central Science, an open-access journal. The equipment required for the test is already available in most biochemistry labs. Laura Kiessling, the Novartis Professor of Chemistry at MIT, is the senior author of the study.
Neutralizing or not?
Many vaccines targeting SARS-CoV-2 focus on the spike protein, which facilitates the virus’s entry into host cells via the ACE2 receptor. The spike protein is covered in sugar chains that are typical of viral envelope proteins. Dr. Kiessling, an expert in protein-carbohydrate interactions, speculated whether it was possible to create a unique “fingerprint” of antibodies based on their interactions with the sugar molecules present on the spike protein.
Traditionally, determining whether an antibody is neutralizing or not requires complex assays to test its ability to block virus entry into cells. However, Dr. Kiessling’s team aimed to develop a quicker method by creating a panel of lectins (proteins that bind to carbohydrates) sourced from various organisms, primarily plants and bacteria. Lectins typically engage with the end of sugar chains as they extend from a protein, participating in activities like cell-cell interactions and immune responses.
To construct the fingerprint, the researchers exposed the SARS-CoV-2 spike protein to these lectins. Each lectin bound to a distinct subset of sugar molecules on the protein. Subsequently, serum containing antibodies against SARS-CoV-2 was added. Antibodies with a high affinity for the spike protein displaced the existing lectins.
Since each antibody displaces a specific set of lectins based on its binding specificity, this displacement could be measured using an enzyme-linked lectin assay (ELLA). By evaluating how each antibody affected the binding of 28 different lectins to the spike protein, the researchers identified distinct patterns of lectin displacement, thereby creating a unique fingerprint for each antibody.
Initially, the researchers established fingerprints for antibodies already known to be neutralizing or non-neutralizing. They then analyzed patient blood samples and determined whether the antibodies present had neutralizing capabilities by comparing them to the fingerprints generated by the known neutralizing antibodies.
Through this analysis, the researchers observed that neutralizing antibodies exhibited distinct patterns compared to non-neutralizing antibodies. This breakthrough enabled the rapid identification of neutralizing antibodies based on their lectin displacement patterns, offering a promising avenue for antibody analysis in the context of viral infections.
Furthermore, utilizing this approach, the scientists successfully categorized antibodies based on whether individuals had received the Moderna or Pfizer COVID-19 vaccines. These vaccines target slightly different viral RNA sequences.
Recognizing the potential of this technology, the researchers have filed a patent for it. They envision its development for rapid testing in a doctor’s office, enabling the determination of an individual patient’s antibody profile.
Dr. Kiessling believes that this technique could be adapted to identify neutralizing antibodies against new variants of SARS-CoV-2 or other viruses that cause diseases. With the existing panel of lectins for the test, the researchers would only need to re-analyze known neutralizing and non-neutralizing antibodies to establish their respective fingerprints.
“The same panel of lectins could be employed for all SARS-CoV-2 variants of concern,” states Dr. Kiessling. “It has the potential to be valuable for emerging viruses, as long as they possess a viral envelope.”