Using proteins to test for COVID antibodies

When the COVID-19 pandemic started in Norway, we needed to find out who had immunity to the coronavirus SARS-CoV-2. I realized that a technology I had developed could be adapted to measure antibodies against viruses.

For years, I had been developing a way of using antibodies as a tool to ‘capture’ and measure thousands of other antibodies and proteins simultaneously. It offered an alternative to mass spectrometry, which is the usual way of measuring proteins, but is super expensive and not very fast. We named the technique microsphere affinity proteomics, or MAP, and published a paper¹ in Nature Methods in 2018.

MAP makes use of beads called microspheres that have fluorescent barcodes able to detect thousands of antibodies. It is similar to a technology developed by Luminex in Austin, Texas. During the pandemic, a large number of companies and public-health laboratories have used Luminex beads to measure antibodies to SARS-CoV-2.

We teamed up with a colleague at Oslo University Hospital, and rapidly screened thousands of people to see whether or not they had antibodies to the virus. We also worked with the Norwegian Institute of Public Health, which already had population studies under way for other purposes.

Early last year, when COVID-19 vaccines became available, we started a big project with other hospitals to assess the efficacy of the vaccines in people with compromised immune systems. There are so many people who have to take drugs that inhibit their immune response — to treat autoimmune conditions, cancer and more. Our laboratory is looking at these people’s antibodies, and a colleague is looking into their cellular immune response, including that of their T cells and B cells.

Immune variations

We have published many articles on this topic. We found that there is huge variation in the effect of immunosuppressive drugs on the immune response to vaccination. As expected, we found that medications that deplete B cells, such as the monoclonal antibodies used to treat rheumatoid arthritis² and multiple sclerosis³, greatly suppress antibody production. Also, people who receive organ transplants use medication that inhibits their production of T cells. These people often have severely deficient antibody production, but benefit from repeated vaccine doses⁴.

This is the work we have been doing for pretty much the past year. Part of it is routine lab work, screening thousands of blood samples. The other part is updating the technology and the assays so that we can detect antibodies to all of the SARS-CoV-2 variants. We modify the assays with spike proteins from new variants as soon as we can make them in-house or they become commercially available. Some proteins are more difficult to produce than others.

I spend most of my time analysing lab data and interacting with clinicians whose patients are on immunosuppressant drugs. In 2020, I was in the lab every day to develop the methods. Now, I’m in there every now and then to troubleshoot things. Lab work is a little bit like a restaurant kitchen — sometimes something goes wrong, and then the head chef has to come in and find out what happened.

Working in a research hospital gives you certain advantages. It would have been difficult to organize the logistics of this study by ourselves and get all the samples. But at the hospital, patients are already seeing a whole team of people who take their blood and organize the lab tests.

We’re benefiting from the hospital infrastructure. It’s very important to think about this research as a whole team effort.