Scientists at Johns Hopkins Meet the Moment with a Saliva-Based Serological Assay for COVID-19 by Heather Darby
During the COVID-19 pandemic, many biologists stepped away from their usual research areas and redirected their labs’ focus to SARS-CoV-2. Some labs, however, have been working on alternatives to traditional serology assays for some time now, including Dr. Chris Heaney’s team at Johns Hopkins University, whose work over the last several years helped prepare for this exact situation. As the virus swept across the United States, Dr. Heaney and his lab were able to put their tools and expertise to use contributing to the pandemic response from the start. Dr. Heaney runs the Environmental Health Microbiology and Immunology Laboratory at Johns Hopkins where a team of scientists develop saliva-based serological assays for pathogens ranging from norovirus to Zika virus. “We had been working for years to show that the measurements you could make in saliva to detect pathogen-specific antibody responses could be equivalent to blood testing,” Dr. Heaney said. The focus on saliva came from a strong push to improve the patient experience with a non-invasive sample alternative to blood. When the COVID-19 pandemic hit, two things became clear very quickly: first, serological testing would be important to capture the true rate of exposure, and second, the need for widespread and regular testing called for a sample type that could be collected more easily than blood. For Dr. Heaney’s team, this was the perfect opportunity to contribute. They turned to xMAP® Technology, which had been the cornerstone of their previous saliva-based assays. “Saliva is a very tricky matrix,” Dr. Heaney noted. It varies widely between people, and even within the same person at different times of day. It does not perform well in solid-phase ELISAs, or with other technologies that require binding to a substrate. With xMAP Technology, though, reactions occur in solution and free-floating beads are more likely to interact directly with saliva content. Metrics such as sensitivity and specificity are significantly better for saliva-based assays run on xMAP Technology compared to solid-phase ELISAs, Heaney said. Multiplexing was also key to devising a high-quality assay. “Based on experience, we knew that if you have some duplication or some slight overlap in the multiplex antigens, it can produce better signals
in saliva, where you’re chasing a much lower concentration of leaking signal from blood into the oral compartment,” Dr. Heaney added. “Using different immunogenic targets is important to telling the full serological story.” Early in the pandemic, his team designed a multiplex assay to test for antibodies to many different SARS-CoV-2 antigens, including nucleocapsid, the receptor-binding domain, and spike proteins. Heaney compared results from this assay to blood-based serology tests and was thrilled to see comparable sensitivity and specificity performance. “With combinations of multiple nucleocapsid, receptorbinding domain, and spike protein antigens, the assay is exquisitely sensitive and specific,” he said. “We can even distinguish between individuals who have had natural infection or the vaccine.” This highly accurate, saliva-based assay made it possible for clinical researchers at Johns Hopkins to develop contactless protocols for clinical study participants and other people in need of serological testing—a measure that helped protect both those being tested and the university staff. Patients could even mail in their samples, making collection easy for everyone. Today, Dr. Heaney’s RUO test is up and running in a CAP/CLIAaccredited pathology lab at the Johns Hopkins Hospital, where it’s being used to report results to participants in clinical studies. “It’s a big milestone,” Dr. Heaney shared. “As vaccines are now more widely available, we can describe that sero-epi part of the story and fill some knowledge gaps about an individual’s exposure to the virus or response to the vaccine.” For his part, Dr. Heaney is just glad his lab could make a difference for people in the pandemic. “This is the biggest global health challenge of our generation,” he said. As scientists and healthcare workers continue to focus on the complex global threat caused by the COVID-19 pandemic, there are many downstream challenges we’ll have to navigate in the coming years. Multiplexing is a powerful tool that scientists around the world use to support assay development innovation and expand discovery in their research. If you’d like to get started building your own immunoassays, download our free xMAP Cookbook to learn more.
xMAP® INSIGHTS | June 2021 6
Luminex supports life science research with our Research Use Only (RUO) product portfolio. Not for use in diagnostic procedures.
