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Often underestimated, influenza B viruses can cause significant illness and mortality, especially in children. Despite the burden of influenza B viruses globally, they remain understudied and little is known about how the immune system interacts with these viruses. 

A team of scientists, led by University of Melbourne Professor Katherine Kedzierska, Head of the Human T cell Laboratory at the Doherty Institute, set out to change this by delving into the intricacies of the immune response to influenza B viruses, revealing a wealth of insights previously overlooked. 

Published in Nature Communications, the study focused on killer T cells, also known as CD8+ T cells, which play a crucial role in the antiviral immune response, and discovered how they target influenza B viruses to combat infection.  

University of Melbourne Tejas Menon, Graduate Researcher at the Doherty Institute and co-first author of the paper, described the challenge of identifying the specific parts of the influenza B viruses that killer T cells bind to as like searching for a needle in a haystack. 

“To tackle a virus, killer T cells need to be able to recognise the virus and find the best viral parts to target,” explained Mr Menon.  

“As new variants of a virus emerge, killer T cells can recognise fragments that are unchanged among those influenza variants. This makes killer T cells an attractive immune population to stimulate with vaccines. 

“In the context of influenza B viruses, we were excited to discover nine viral fragments which provoked a strong immune response from killer T cells and remained unchanged in the ‘virus' history’. This finding, reached after sieving through hundreds of influenza B virus particles, which was done in collaboration Professor Purcell and Dr Illing from Monash University, is a significant advancement in our understanding of influenza B immunity.” 

Until now, only 18 such viral fragments had been identified, limiting the ability to generate new vaccines against influenza B viruses that prevent severe illness and death. This comprehensive study brings the total to 27, offering more options for vaccine development. 

Researchers also explored how this immune response changes with age, providing valuable information for tailoring health strategies for different age groups.  

University of Melbourne Dr Carolien van de Sandt, a Senior Research Fellow at the Doherty Institute and co-author of the study, said that this research gives valuable insights into age-related immune responses to influenza B viruses. 

“As we age, our immune system responds differently to the flu,” said Dr van de Sandt. 

“While we detected killer T cells that recognise influenza B viral fragments across the human lifespan, from young children to the elderly, those T cell responses substantially peaked in adults. This may help explain why this particular age group is protected from severe influenza B infections.  

“Our findings also showed that killer T cells that recognise influenza B viruses have a very good memory, but are not as numerous in elderly people and children. This is fascinating, as children have a higher burden from influenza B than adults and the elderly.”  

Professor Kedzierska explained that the clinical implications of the study are substantial, and the research presents the first step toward the development of new T cell-based influenza B vaccines. 

“The influenza B viral T cell targets that we have found could be included in new T cell-based vaccines, which could significantly reduce severe cases and death caused by influenza B, especially in children, and alleviate the burden of seasonal influenza epidemics,” said Professor Kedzierska. 

Current influenza vaccines primarily rely on antibodies that target specific strains, necessitating frequent updates due to mutations in the virus. However, the study suggests exploring T cell-based vaccine strategies, highlighting their potential to provide broad immune protection across all variants of influenza B viruses for various age groups. 

Peer review: Menon T, Illing P, Chaurasia P, et al. CD8+ T-cell responses towards conserved influenza B virus epitopes across anatomical sites and age. Nature Communications (2024). DOI: https://doi.org/10.1038/s41467-024-47576-y  
 

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.