Two teams explore the impact of the first flu on the immune system

Two teams explore the impact of the first flu on the immune system

June 05, 2019 Source: Nature Natural Science Research

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Recently, the National Institutes of Health (NIH) approved two large grants to fund the first large-scale long-term study on how the baby's first exposure to the flu will affect its immune system. Researchers will conduct long-term follow-up of the baby from birth to determine how the immune signature left in the early years will affect the individual's ability to cope with different influenza strains in the future.


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These studies also help explain why individual effects of flu vaccines are individual and if the child is exposed to a wild-type flu virus before vaccination with an attenuated flu vaccine, is it more protective and lasting? Furthermore, the results of these studies may provide clues to the development of universal influenza vaccines that provide life-long resistance to most seasonal influenza strains.

Paul Thomas, an immunologist at the St. Jude Children's Research Hospital in the United States, and Aubree Gordon, an epidemiologist at the University of Michigan, Ann Arbor, formed a team that won the NIH's National Institute of Allergy and Infectious Diseases (NIAID). 7 years, a total of 35 million US dollars in funding. The team will establish long-term follow-up babies in Nicaragua, Los Angeles, and Wellington, New Zealand. The team led by epidemiologist Mary Allen Staat of the Cincinnati Children's Hospital Medical Center received another grant for a seven-year, $31 million team that will establish a maternal and child cohort in Mexico City and Cincinnati.

Influenza vaccine "new target"

Influenza viruses continue to mutate, and the strains that are prevalent each season are different from the previous ones. Therefore, we have to develop new vaccines for each new influenza season. The current seasonal flu vaccine is not ideal and its protection can only last for several months.

However, the first influenza virus strains in childhood may affect the individual's response to the current influenza virus strain and related vaccines during the specific flu season. This is the so-called "imprinting": the pathogen (viral) strain first encountered in childhood will leave an indelible mark on the individual's immune system and produce a lifetime of protection against similar virus strains. Other pathogens that are present do not have this protective effect. This type of immunoblotting also gives people a stronger protection when vaccinating vaccines of similar strains than when vaccinating non-similar strains.

Infants born in different flu seasons are not the same as the virus strains they are exposed to, and the immunoblots produced are different. Therefore, a population can be seen as a collection of individuals with varying susceptibility to different strains.

The “immunoblotting” doctrine has given scientists hope for a more durable and broader universal flu vaccine. “I think it’s very meaningful for NIAID to allocate funds to research aimed at determining how the history of childhood flu exposure affects an individual’s future immune response to the flu virus,” said Scott Hensley, a virus immunologist at the University of Pennsylvania. “These studies may reveal why. Existing vaccines are ineffective for some people, and these findings are likely to provide direct clues to the actual improvement of existing vaccines or the development of new vaccines."

Antigen priority

Scientists don't know much about the exact mechanism by which a baby produces an imprint of influenza. One such theory is called "antigen-preferred", in which a strain of virus that is exposed to childhood is given a "priority" position in the immune response, while later exposed strains are placed in less important locations. "Although it is generally accepted that 'immunoblotting' does have something to do, the regulatory mechanism behind it is still basically a black box," said Matthew Miller, a flu immunologist at McMaster University in Canada.

These two large infant cohort studies will provide an unprecedented opportunity to unravel the secrets of imprints. Of particular note is Nicaragua, which has many platforms for recruiting newborns and collecting analytical samples, as the region is home to the NIAID-funded Nicaragua Pediatric Influenza Cohort Study, which has been in existence since 2011. Infants have been recruited to study the incidence and severity of childhood flu. Therefore, Gordon, head of the Children's Flu Cohort Study, said she hopes to start recruiting new subjects before July.

According to Gordon, their joint team will recruit 2,200-3,500 children at three research sites, including 930 infants who have been recruited in Nicaragua, with blood samples and detailed growth history. Recruitment in California and New Zealand will last for three years and will be followed up for seven years with NIAID funding, but they hope to find more funding to further extend the study until the child enters adolescence or even longer. Nicaragua will continue to recruit within 7 years and follow-up until the subject reaches the age of 15.

Cincinnati and Mexico City plan to recruit 1080 babies, 360 people a year for 3 years, and follow up during the funding period. Staat also hopes to seek more funding to extend the follow-up time.

Single immune cell RNA sequencing

Researchers will regularly collect blood and other samples from infants, classify hundreds of thousands of cells in the sample using newly developed techniques, and then sequence RNA from individual immune cells to track genes at different time points and exposure to influenza viruses. The law of change in activity. Thanks to these technological innovations, researchers were able to perform a thorough and comprehensive analysis of immune cells and other components of the immune system.

Researchers can analyze samples collected at the same time in the same individual—before and after the imprinting event, during influenza infection, during influenza rehabilitation, before and after flu vaccine. Thomas hopes to use this study to establish a model of the response of the child's immune system to influenza and influenza vaccines. The main determinants are the history of influenza exposure in children and the type of influenza virus exposed. "This study is very successful once it is successful," Miller said.

The two funded groups have begun to get in touch with each other to find the best way to work together. "I hope that we can achieve 1+1>2 effect through cooperation and complementarity," Staat said.

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