Every winter, influenza returns with a new variant. People who have previously been infected with or vaccinated against flu may have some protection, but this depends on how well their immune system’s “memory” of the previous virus or vaccine cross-reacts with the new variant. At present, there is no good way to measure this. A new NIH-funded project by researchers at the University of California, Davis and Johns Hopkins Bloomberg School of Public Health aims to solve that problem with a new device to measure this immune system “memory” in the blood. 

“There’s no way to assess if the immune system is prepared for the next mutant flu virus, so we need a new vaccine every year,” said Steven George, professor of biomedical engineering at UC Davis and co-principal investigator on the grant. “We’re trying to figure out if you have white blood cells that can respond quickly to a new variant.” 

When you are exposed to a virus, white blood cells called B-cells expand and differentiate. Many of these cells become plasma cells pumping out antibodies to deal with the virus right away. Others become memory B cells, biding their time until the same or similar virus comes back. If it does, they can rapidly activate and attack the infection with antibodies. 

Currently, it’s possible to measure circulating antibodies, produced by plasma cells, but this fades with time. It’s much more difficult to measure whether memory B cells are present and how effective they may be against a new variant of the same virus. 

Working with immunologist Nicole Baumgarth, formerly at UC Davis School of Veterinary Medicine and now at Johns Hopkins, George’s lab developed a prototype device that measures memory B cells based on how well they can stick to a surface by recognizing the virus under shear flow. They call the method Shear Activated Cell Sorting, or SACS. 

Microfluidic chip

The device is based on a microfluidic chip with tiny channels. The floor of the channel is coated with flu virus. As white blood cells flow through the channels, memory cells that recognize virus proteins (or antigens) will stick to them. By controlling the flow rate, it is possible to measure how tightly the cells can stick: As the flow rate increases, shear forces on the cells increase and pull them off. 

By counting the cells as they stick and get washed out at different flow rates, it is possible to measure their binding affinity, or how well they stick to the virus in the channel. Scientists can then compare how well the cells bind to the original virus they were “trained for” and a new variant. 

The goal is to develop a device that could be used by public health labs to measure immunity to a new influenza variant in the population as a whole, helping to guide public health responses, rather than for individual patients, George said. The device could also be used to measure immunity to variants of SARS-CoV-2 and other viruses. 

Additional co-investigators are Professor Xiangdong Zhu, UC Davis Department of Physics and Venktesh Shirure, a project scientist in the Department of Biomedical Engineering.

The grant of about $4 million over five years is funded by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health.