A new study from the School of Molecular & Cellular Biology seeks to better understand shedding patterns among common respiratory viruses by closely examining the immune system before, during, and after infection.

The FLUdetect study, headed by Chris Brooke, an associate professor of microbiology, and Nicholas Wu, an assistant professor of biochemistry, aims to learn more about specific features of the immune response to improve infection control.

“We’re trying to capture a high-resolution quantitative profile of how common respiratory viruses like influenza virus or RSV shed over time and how our immune system responds to these infections,” Brooke said. “That kind of data doesn’t currently exist for most of these viruses.”

Researchers have recruited 15 participants for the initial rollout of the study, which is projected to last three months, and plan on recruiting at least 35 more during flu season next fall. Participants will submit twice weekly nasal swabs, which will be PCR tested against nine common families of viruses including influenza, RSV, and seasonal coronaviruses, which are distinct from SARS-CoV-2. If a participant tests positive, they will provide daily samples for 14 days, as well as a series of blood draws.

Although PCR testing alerts researchers to the identity of the broader virus family, they must sequence the virus to distinguish the specific strain. Brooke hopes that in depth analyses of blood samples will provide insight into immune correlates of protection, or immune features that may be associated with reduced viral shedding and infectiousness. Identifying these immune correlates of protection can be used to improve vaccine design, he explained.

‘If we know the feature of immune response, we can better control infection,” Brooke said. “And if we can identify those immune features, we can design better-targeted vaccines in addition to evaluating the vaccines that we already have.”

Participant samples will also provide data on the B-cell repertoire, or the library of antibodies our bodies produce.

“The entire point of vaccination is to deliver instructions to the immune system for how to make the type of immune response that is thought to be protective against a certain virus,” Brooke said, emphasizing that little is known about immune system communication and how it is governed. The more researchers are able to learn about changes to the immune system during infection, the more effectively they will be able to develop vaccines that instruct specific responses.

The FLUdetect study is modeled off the SHIELD initiative, a first-of-its-kind program designed to detect SARS-CoV-2 in the initial days of infection. The former has expanded to detect dozens of virus strains. FLUdetect differs from traditional study designs by collecting a high frequency and volume of samples from a relatively small number of participants, as opposed to one or two samples from hundreds or thousands of subjects.

Most virus studies capture symptomatic patients in the clinic when their infection is almost resolved. But FLUdetect profiles participants before, during, and after infection, allowing researchers to generate a high-resolution profile of infection dynamics.

Enrollment will re-open in the fall with an expanded cohort to capture flu season. Brooke hopes the study can be extended over several years to profile variation amongst viruses and examine how newly evolved variants compare to their original counterparts.

“There’s an urgent need to identify immune correlates of protection against influenza virus and other viruses,” Brooke said. “If we better understand the specific features of immune response that effectively control these viruses, we can design vaccines that are better able to prevent someone from spreading virus to their friends or family.”

Editor’s note: The FLUdetect study is housed at the Institute of Genomic Biology and is funded by the National Institute of Allergy and Infectious Diseases and the Centers of Excellence for Influenza Research and Response Network.

Photo courtesy of Fred Zwicky.