New test may predict Covid-19 immunity. MIT News

Most people in the United States have some degree of immune protection against Covid-19, either through vaccination, infection, or a combination of the two. But how much are individuals protected?

Researchers at MIT have developed an easy-to-use test that might be able to answer that question. Their test, which uses the same type of “lateral flow” technology as Covid-19’s most rapid antigen test, measures levels of neutralizing antibodies targeting the SARS-CoV-2 virus in blood samples.

Easy access to this type of testing could help people decide what precautions to take against Covid infections, such as getting extra booster shots, the researchers said. They have applied for a patent for this technology and now hope to partner with a diagnostic company that can manufacture the device and obtain FDA approval.

Hojun Li, Charles W. and Jennifer C. Johnson Clinical Research Fellow at MIT’s Koch Institute for Integrative Cancer Research, said: “But the test could make the biggest difference in people undergoing chemotherapy, taking immunosuppressants for rheumatic or autoimmune diseases, the elderly and the general public.” These are all people who may need to be boosted sooner or given higher doses to achieve adequate protection.”

The test was designed to swap spike proteins from different viruses so it could be modified to detect immunity to existing or future variants of SARS-CoV-2, researchers say. said.

Li, who is also the attending physician at the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, is a senior author on the study, which is published online today. Cell report methodGuinevere Connelly, a former research engineer at the Koch Institute and now a graduate student at Duke University, and Orville Kirkland, a research assistant at the Koch Institute, are the lead authors of the paper.

simple test

Li, who joined the Koch Institute in the fall of 2019, studies blood cell development and how blood cells become cancerous. When SARS-CoV-2 emerged, he started thinking about how to fight the pandemic. With many other researchers already working on diagnostic tests for infectious diseases, he turned his attention to developing tests that would reveal how well protected his immunity was against Covid-19. .

Currently, the gold standard approach for measuring immunity involves mixing a blood sample with live virus and measuring the number of cells in the sample that are killed by the virus. That procedure is too risky to be performed in most labs, so more commonly used approaches include non-infectious modified ‘pseudovirus’ particles or ELISAs that can detect antibodies that neutralize the fragments. It is based on a test called (enzyme-linked immunosorbent assay). of viral proteins.

However, these approaches require laboratory-trained personnel with specialized equipment, making them impractical for immediate results in a physician’s office. Li wanted to come up with something that could be easily used by healthcare professionals and even at home. He was inspired by an at-home pregnancy test based on a type of test called the Lateral Flow His Assay.

Lateral flow assays typically consist of strips of paper embedded with test lines that bind to specific target molecules when present in the sample. This technology is also the basis for most rapid home tests for Covid-19.

Lacking experience with this type of test, Li contacted two faculty members at MIT who had expertise in devising diagnostics based on lateral flow assays. Associate Professor of Chemical Engineering, she is Sangeeta Bhatia of Hadley Sikes and John and Dorothy. Professor Wilson is Professor of Health Sciences and Technology, Electrical Engineering and Computer Science, and a member of the Koch Institute.

With their help, his lab blocks the SARS-CoV-2 receptor-binding domain (RBD) from binding to ACE2, the human receptor the virus uses to infect cells. We have developed a device that can detect the presence of antibodies.

The first step in the test is to mix a human blood sample with the viral RBD protein. It is labeled with tiny gold particles that can be visualized when bonded to a piece of paper. After allowing time for the antibodies in the sample to interact with the viral proteins, a few drops of the sample are placed on a test strip with two test lines embedded in it.

One of these lines attracts free viral RBD proteins and the other RBD captured by neutralizing antibodies. A strong signal from the second line indicates high levels of neutralizing antibodies in the sample. There is also a control line that detects free gold particles, ensuring that the solution is flowing across the strip.

To develop the reagents needed for the test, members of Li’s lab worked with Angela Koehler, an associate professor of biotechnology, and David H. Koch, a member of the Koch Institute, and Michael Yaffe, a professor of science. cooperated.

Prediction of immunity

In addition to a test cartridge containing paper test strips, the test kit also includes a finger prick lancet that can be used to take small blood samples of less than 10 microliters. This sample is mixed with the reagents required for testing. After approximately 10 minutes, the sample is exposed to the test cartridge and results are available in 10 minutes.

The output can be read in two different ways. One is to look at the line that indicates whether neutralizing antibodies are present. Alternatively, use the device to measure the intensity of each line and use a smartphone app that can calculate the ratio of neutralized RBD protein to infectious RBD protein to obtain a more accurate measure of antibody levels. I can. If this ratio is low, it may suggest another booster shot is needed or extra precautions should be taken to prevent infection.

Researchers tested the device on blood samples taken from about 60 people infected with SARS-CoV-2 and 30 people who were not infected in December 2020. They were able to detect neutralizing antibodies in samples from people previously infected with the virus. This was similar in accuracy to existing laboratory tests. They also tested 30 consecutive samples from two individuals before receiving the mRNA Covid-19 vaccine and at several time points after vaccination. Levels of neutralizing antibodies in vaccinated individuals peaked approximately 7 weeks after the first dose and began to decline slowly thereafter.

Previous research on SARS-CoV-2 and other viruses has shown a strong correlation between the amount of neutralizing antibodies circulating in an individual’s bloodstream and the likelihood of infection.

Li says the test can be easily adapted to different variants of SARS-CoV-2 by swapping reagents specific for the variant’s RBD of interest. Researchers now hope to partner with diagnostic companies that can produce tests in bulk and get FDA approval for their use.

This study was funded by a Koch Institute Supporting (Core) Grant from the National Cancer Institute, the American Society of Hematology Scholarship Award, the National Institutes of Health, and the Charles and Marjorie Holloway Foundation.