Saturday, July 13, 2024

First impressions matter: New insights into long-term protection from the flu

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Researchers have made an important discovery that could explain why some people experience more severe flu infections than others.

The study, led by University of Melbourne’s Dr Marios Koutsakos, Research Fellow at the Peter Doherty Institute for Infection and Immunity (Doherty Institute) and published in Nature Microbiology, found that people develop stronger immune responses to the variants of influenza B they were exposed to during their childhood. This early exposure to the virus impacts how well their immune system can recognise new variants and protect against them.

If newer influenza B variants share similar characteristics with strains that were circulating during an individual’s first five to ten years of life, their body will exhibit a stronger immune response than for strains with many differences.

Previous epidemiological studies have noted differences in susceptibility and severity of influenza infections based on year of birth, suggesting a link between childhood exposure to influenza and subsequent lifelong immune responses to the virus.

“The purpose of our research was to provide robust immunological evidence to support these observations,” said University of Melbourne’s Peta Edler, Research Assistant in Biostatistics at the Doherty Institute and first author of the paper.

The researchers analysed samples collected from people born between 1917 and 2008 in both Australia and the United States. Specifically, they measured and compared antibodies to influenza B strains circulating globally between 1940 and 2021.

“Using this comprehensive dataset, we discovered that the highest concentrations of antibodies in each sample generally corresponded with the dominant strain of influenza B virus that was circulating during that individual’s childhood,” Ms Edler said.

“Essentially, when it comes to influenza B virus infections, first impressions matter. The initial, early-life exposure to the virus appears to influence how the immune system responds to future influenza B viruses.”

While generally less common than influenza A infections, influenza B still accounts for a substantial proportion of cases annually, with a high morbidity and mortality burden, particularly for children and people under 18 years old.

According to Dr Koutsakos, establishing an immunological link between initial exposure to influenza B and long-term immune responses opens new pathways for vaccination and the public health response to manage these risks.

“Our research could help predict which populations are most at risk of disease during each flu season, which would guide the development of public health strategies targeting specific age groups,” said Dr Koutsakos.

“Moving forward, we want to explore what drives this long-term immunity and find out whether our immune system behaves the same way following its first exposure to influenza A. This work could uncover potential targets for the design of new vaccines, but also inform tailored immunisation strategies.”

Peer review: Edler P, et al. Immune imprinting in early life shapes cross-reactivity to influenza B virus haemagglutinin. Nature Microbiology (2024). https://doi.org/10.1038/s41564-024-01732-8

Funding: National Health and Medical Research Council, Australian Research Council, National Institutes of Health (USA), The Clifford Craig Foundation, Research Grants Council (Hong Kong), Michelson Medical Research Foundation, Monash University, University of Melbourne and National Institute of Allergy and Infectious Diseases (NIAID) (USA).

Collaboration: This study was a multi-institute collaboration between the Doherty Institute, University of Melbourne, Monash Biomedicine Discovery Institute, Deepdene Surgery and University of Tasmania.

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