From Spanish flu to today: how immune cells keep up with a changing virus
In a breakthrough for influenza research, scientists have discovered immune cells that can recognise influenza (flu) viruses even as they mutate, raising hopes for a longer-lasting vaccine and a universal protection against future flu pandemics
University of Melbourne
The flu virus is constantly evolving, meaning immunity from past infections or vaccinations may not fully protect against new strains. These mutations are why last year’s flu vaccine may no longer be effective, requiring annual updates to keep up with the latest variants.
But what if our immune system could recognise a broader range of flu viruses, providing longer-lasting protection? New research suggests that certain immune cells, a subset of T cells, might hold the key.
Research led by the Peter Doherty Institute for Infection and Immunity (Doherty Institute) and Monash University has uncovered how specific T cells, which play a critical role in fighting infections, can detect multiple flu strains, even those that have evolved over a century. This process, known as cross-reactivity, could be crucial in developing more effective immunity against influenza.
In the study, published in Science Immunology, researchers analysed samples from individuals with different flu viruses and identified a subset of T cells that recognise a particular protein present in influenza A viruses, from the 1918 Spanish flu to the latest 2024 H5N1 strains.
The University of Melbourne’s Dr Oanh Nguyen, Senior Research Fellow at the Doherty Institute and co-author of the study, explained the molecular mechanisms that enable these T cells to recognise multiple influenza variants.
“We tested how people’s T cells respond to a specific part of the influenza virus that changes frequently. Over the last 100 years, this region has evolved into 12 different forms,” said Dr Nguyen.
“We found that some individuals have T cells that can recognise up to nine of these variants, while others have T cells that can only detect a couple.”
Professor Jamie Rossjohn, Immunologist at Monash University and co-senior author of the study, explained how the team uncovered the molecular details behind this immune response.
“This work reveals an untapped ability of the immune system to respond to flu viruses, even as they change over time,” said Professor Rossjohn.
“We used an advanced technique called crystallography to determine how T cells see flu viruses at the molecular level. We observed specific interactions between the T cells and the flu proteins that determine why some T cells are better at detecting a wide range of strains than others.
“While our findings deepen our understanding of how T cells react to changing flu viruses, they are also highly relevant for understanding immune responses to other rapidly evolving viruses such as SARS-CoV-2.”
The flu remains a major global health threat. According to the WHO, flu causes 3 to 5 million cases of severe illness and up to 650,000 respiratory deaths each year, particularly among vulnerable populations.
The University of Melbourne’s Professor Katherine Kedzierska, Head of the Human T cell Laboratory at the Doherty Institute, said a universal vaccine, one that protects against multiple strains for longer periods, would be a game changer.
“This research is hugely significant. It shows how certain T cells can recognise multiple flu strains, which is a big step towards understanding universal protective immunity – not just for the flu, but potentially for other viral diseases too,” said Professor Kedzierska.
“Harnessing these cross-reactive responses could be the key to a vaccine that offers longer-lasting protection and reduces the risk of future flu pandemics.”
## END ##
Additional information:
- Peer-reviewed paper: Quiñones-Parra S, Gras S et al. Molecular determinants of cross-strain influenza A virus recognition by αβ T cell receptors. Science Immunology (2025). DOI: http://doi.org/10.1126/sciimmunol.adn3805
- Collaboration: This study is the result of a major collaborative effort between the Doherty Institute and Monash University.
- Funding: This work was supported by the National Health and Medical Research Council of Australia (NHMRC), the University of Melbourne, a Consejo Nacional de Ciencia y Tecnología Scholarhip (Mexico), a Victoria-India Doctoral Scholarship and the Research Grants Council of the Hong Kong Special Administrative Region (China).
Journal
Science Immunology
Method of Research
Experimental study
Subject of Research
Cells
Article Title
Molecular determinants of cross-strain influenza A virus recognition by αβ T cell receptors
Article Publication Date
7-Feb-2025
Influenza A viruses adapt shape in response to environmental pressures
NIH study identifies previously unknown adaptation
image:
Colorized transmission electron micrograph of influenza A/H3N2 virus particles, isolated from a patient sample and then propagated in cell culture. Influenza A virus particles adapt shape—as filaments and spheres—to help them infect cells depending on environmental conditions. A group of virus particles exhibiting these diverse shapes have been highlighted in teal.
view moreCredit: NIAID
WHAT:
Influenza A virus particles strategically adapt their shape—to become either spheres or larger filaments—to favor their ability to infect cells depending on environmental conditions, according to a new study from National Institutes of Health (NIH) scientists. This previously unrecognized response could help explain how influenza A and other viruses persist in populations, evade immune responses, and acquire adaptive mutations, the researchers explain in a new study published in Nature Microbiology.
The study, led by intramural researchers at NIH’s National Institute of Allergy and Infectious Diseases (NIAID), was designed to determine why many influenza A virus particles exist as filaments. The filament shape requires more energy to form than a sphere, they state, and its abundance has been previously unexplained. To find the answer, they developed a way to observe and measure real-time influenza A virus structure during formation.
The researchers found:
- Influenza A viruses rapidly adjust their shape when placed in conditions that reduce infection efficiency, such as the presence of antiviral antibodies or host incompatibility.
- A virus’ shape is dynamic and impacted by its environment, rather than being fixed by strain, as commonly believed.
- The study assessed 16 different virus-cell combinations that resulted in predictable shape trends.
Prior experiments by the research team showed that influenza A virus filaments can resist inactivation by antibodies, and the team is working to understand exactly how antibodies influence shape and infection efficiency. They also anticipate learning how viral mutations affect the shape of the virus. Many other viruses—such as measles, Ebola, Nipah, Hendra and respiratory syncytial virus—also incorporate a mixed-shape infection strategy, the researchers note.
ARTICLE:
E Partlow et al. Influenza A virus rapidly adapts particle shape to environmental pressures. Nature Microbiology DOI: 10.1038/s41564-025-01925-9 (2025).
WHO:
Tijana Ivanovic, Ph.D., is chief of the Single Virion Biology and Biophysics Unit in the NIAID Laboratory of Viral Diseases.
CONTACT:
To schedule interviews, please contact the NIAID News Office, (301) 402-1663, niaidnews@niaid.nih.gov.
NIAID conducts and supports research—at NIH, throughout the United States, and worldwide—to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID website.
About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit https://www.nih.gov/.
NIH...Turning Discovery Into Health®
Journal
Nature Microbiology
