A researcher at Ann Arbor’s University of Michigan has teamed up with international researchers to study how first flu exposures can affect future exposures. The research is funded by a $35 million, seven-year National Institutes of Allergy and Infectious Diseases grant.
“The grant will allow us to look at imprinting, which is this idea of how your first flu exposure affects future exposures,” says Aubree Gordon, assistant professor of epidemiology and leader of the research. “And it’s fitting that this work, originally observed and written about at the University of Michigan, will continue to be studied, at least in part, here.
“We’ve actually realized that flu exposure history probably affects your susceptibility to additional influenza infections, although we don’t really understand why. It probably explains why sometimes the vaccine works really well in certain age populations and not others.”
The grant will allow Gordon and colleagues in Nicaragua to continue the cohort she’s been leading there since 2011 and add similar cohorts in Los Angeles and New Zealand. Collaborators include researchers from other U.S. institutions and Australia.
“These cohorts provide a unique opportunity to define the basic immunological mechanisms in B and T cells that mediate the imprinting effect,” says Paul Thomas, a member of the St. Jude Children’s Research Hospital Department of Immunology and co-leader of the research. “The fantastic team we’ve assembled will be able to provide an in-depth characterization of the developing immune system.”
Thomas Francis Jr. of U-M’s School of Public Health first argued that a person’s first flu exposure affects subsequent exposures. He also worked Jonas Salk to develop the polio vaccine. U-M was also home to Hunein “John” Maassab, who developed the technology of what would become the nasal-spray flu vaccine FluMist.
Arnold Monto, also of U-M, worked under Francis on the Tecumseh Study, a large-scale, long-range epidemiological study that followed an entire village in an effort to understand the chronic and acute disease dynamics.
Monto and his team vaccinated a large percentage of Hong Kong’s school-age population when the flu pandemic broke out there in 1968, proving that herd immunity worked. He continues to counsel international health organizations such as the World Health Organization and authored many papers, including one published in 2005 warning of the dangers of an avian influenza pandemic.
“University of Michigan researchers have been at the forefront of research on influenza, which continues to be a major threat to global public health,” says F. DuBois Bowman, dean of the U-M School of Public Health. “We’re excited this grant will allow us to continue on this tradition and make a contribution towards one day developing a universal flu vaccine.”
Gordon first became involved in the cohort in Nicaragua as a graduate student while at the University of California, Berkeley. There, she met professor Eva Harris, who had been working with a cohort focusing on dengue research in the same country. Gordon added influenza onto the existing cohort study as part of her dissertation work. In 2010, Harris and Gordon received funding to establish the ongoing flu cohort. Gordon brought it to U-M when she came to the university in 2014.
To recruit newborns into a cohort, researchers talk to mothers during pregnancy and explain what participating entails. Depending on the family’s preferences, they’ll meet at a medical center or the family’s home, collect samples, have ID batches for participants, and conduct surveys on breast feeding and vaccination history, exposure to smoke, size of the house, how many people live there, and access to water. All of these factors are updated regularly. As part of the arrangement, they also provide medical care for study participants.
The team conducts other flu studies, and Gordon collaborates with UC-Berkeley, Nicaragua’s Ministry of Health, and other organizations on a number of studies on mosquito-borne viral illnesses. They follow households for influenza, which has allowed researchers to also look into rates of infection within families. The cohorts have also provided opportunities to do research on how the flu virus spreads and what factors might make it more likely for someone to get the infection as well as vector-borne diseases such as dengue, Zika, and chikungunya.
The original cohort looked at the burden and seasonality of the flu. The expansion will help look at the question of imprinting and repeat infections.