How is lifelong immune response to flu shaped in infancy? St. Jude leads study to find out

The National Institutes of Allergy and Infectious Diseases has awarded St. Jude Children’s Research Hospital a seven-year grant of up to $34.3 million to lead an international effort to define how influenza influences the developing immune system.

The study includes investigators at 12 medical and research centers in the U.S., New Zealand, Australia and Nicaragua. Researchers will follow about 3,000 children for seven years beginning before birth to understand how their first exposure to flu shapes their lifelong immune response to the virus.

“There is evidence that the very first flu virus encountered, whether as an infection or vaccination, ‘imprints’ on the developing immune system and influences the immune response to different flu viruses for decades,” said the study’s principal investigator Paul Thomas, PhD, a member of the St. Jude Department of Immunology, in a statement. Aubree Gordon, PhD, of the University of Michigan, is the other principal investigator.

“This study provides an opportunity to understand how imprinting affects individuals’ immune memory and their ability to confront flu on subsequent exposures,” Thomas said. “Understanding the mechanism could lead to vaccines that ‘train’ the immune response to be longer lasting and able to protect against a wider variety of flu viruses.”

Added Gordon, an assistant professor of epidemiology at UM’s School of Public Health: "A comprehensive understanding of immune responses during natural infections and vaccinations is essential for identifying new correlates of protection, that is, immune responses that may protect us from getting infected with influenza or may protect us from getting sick although they do not prevent infection. This knowledge would be informative for the development an improved influenza vaccine."

St. Jude is a global leader in influenza research. The hospital is a World Health Organization Collaborating Center for Influenza. It is the only center focused exclusively on the threat flu viruses in animals pose to humans. St. Jude is also an NIAID Center of Excellence for Influenza Research and Surveillance. The designation makes St. Jude part of a network developed to provide the information and public health tools needed to control the impact of epidemic influenza and minimize the threat of pandemic influenza.

Flu and complications like pneumonia remain leading causes of death in the U.S. The flu virus is constantly changing and can move between humans and animals with devastating results. Flu pandemics have killed millions worldwide and remain a threat. While imperfect, annual vaccinations against circulating seasonal flu viruses remain the most effective protection.

Researchers hope this study will lay the groundwork for more effective flu prevention strategies, including a universal vaccine to replace yearly flu vaccinations.

Flu viruses are categorized into two groups based on which of the many different haemagglutinin (HA) proteins a virus carries on its surface. Based on their HA surface proteins, currently circulating human flu viruses include group 1 and group 2 viruses. Previous research into pandemic flu outbreaks has found an association between flu susceptibility and flu exposure early in life. The findings suggested that initial exposure to group 1 flu viruses provided enhanced protection against other group 1 flu viruses in the future, but not against group 2 flu viruses. Initial exposure to group 2 viruses seems to have a similar effect.

Researchers are particularly interested in how early flu exposure affects B and T cell production as well as antibody production in response future influenza exposures.

Children enrolled in the study will be recruited by researchers at Children’s Hospital Los Angeles as well as in New Zealand and Nicaragua. Their immune response to flu along with other factors will be tracked through blood samples, which will be stored at St. Jude. The analysis will be conducted by researchers at St. Jude and participating centers.