Cincinnati Children's gets $31 million grant to study flu immune response
The National Institutes of Health (NIH) has awarded Cincinnati Children’s a $31 million U01 cooperative agreement grant that will be paid out over seven years to principal investigator Mary Allen Staat, MD, MPH, professor, Infectious Diseases, and her team. The award is the medical center’s second-largest ever.
The agreement will fund cohort studies of more than 2,000 mother/infant pairs to gain a better understanding of the immune response in babies—specifically, after their first exposure to the flu.
“There’s a theory that the very first exposure you have imprints your immune system, which then affects your response to the next exposure,” Staat explained. “That exposure can come through a vaccine or through a wild-type virus that’s circulating in the community. So, for example, if you get infected with an H1 strain in the first year of life, we want to know if and how that initial infection sets the course for your response to any other flu exposure later in life.”
Researchers hope that finding the answer to that question will help them create a more effective universal flu vaccine.
Cohorts are the key
During the study, known as Influenza IMPRINT Cohort, Staat and her team will work closely with a team in Mexico City headed by Guillermo Ruiz-Palacios, MD, chair of the Department of Infectious Diseases at the National Institute of Medical Sciences and Nutrition. They will also partner with a group from Emory University in Atlanta, led by Jens Wrammert, PhD, assistant professor, Emory Vaccine Center.
Half of the cohorts will be recruited in Cincinnati, and half will be located in Mexico City. Starting in the second trimester of pregnancy, the study will follow the mothers and babies for three to four years. Initially, researchers will look at flu antibody in the mother’s blood and in the cord blood to see how much of it gets passed along to her baby. For mothers who are nursing, they will examine breast milk samples to determine how much antibody the babies are getting. Weekly nasal swabs will also be collected from the infants, as well as frequent blood samples.
“Cohorts are really difficult studies to do,” said Staat. “They’re labor-intensive and a big commitment on everybody’s part, especially the mothers and babies.”
But the Cincinnati Children’s team proved they could be successful, based on another project headed by Ardythe Morrow, PhD, MSc, called PREVAIL, which is being funded by the Centers for Disease Control. That study is following 265 pairs of mothers and infants for two years to examine the natural history and immunology of infections with rotavirus, norovirus, influenza and RSV.
“Ardythe has a long history of knowing logistically how to put cohorts together and make them work,” said Staat. “The Influenza IMPRINT Cohort will build on the success of the PREVAIL cohort and provide the foundation for creating something bigger.”
Quest for the Grail
Developing a universal vaccine for flu is the Holy Grail for the NIH, which has devoted a tremendous amount of thought, preparation and money toward that goal.
Globally, seasonal influenza causes an estimated 1 billion cases annually, with 3 to 5 million cases of severe illness and 300,000 to 500,000 deaths per year. In the U.S., 5 to 20 percent of the population contracts influenza each year. Since 2010, this has amounted to 9 to 36 million cases annually, resulting in 140,000 to 710,000 hospitalizations and 12,000 to 56,000 deaths. Yet only 40-50 percent of the population get immunized.
“People have deep-seated feelings about the flu vaccine,” said Staat. “When I ask parents if their child is up to date on their immunizations, they say, ‘yes.’ Then I’ll ask if the child has had a flu shot, and the answer is often ‘no, I don’t trust it’ or ‘no, it doesn’t work.’ They don’t recognize the dangers of flu, that even healthy kids can get it and have serious complications or die.”
The effectiveness of current flu vaccines varies from year to year, depending on how closely it’s matched to the strains of virus that are circulating. A universal flu vaccine could give broader protection regardless of what strains are active.
Staat is so passionate about her work that she has enlisted the help of her own family members. Daughter Katie and granddaughter Ava graduated from the PREVAIL cohort in April after two years of participation.
“When parents say participating in the study is hard, I understand, because we’re doing it,” she said. “It’s not fun to watch your baby be stuck by a needle. It’s hard to collect all these specimens. But I tell my grandbaby, ‘You are special. With every nose swab and needle stick, we learn something more about what’s happening with you, and that is going to tell us what we need to know to create vaccines to prevent infections in the future. You are a part of history that is so unique, and you’re going to make a difference in the world.’”
