Looking back to protect the future: New insights into influenza immunity

A new study from the Peter Doherty Institute for Infection and Immunity (Doherty Institute) shows that seasonal influenza vaccination does more than protect against viruses circulating that year; it can also prime the immune system to respond to future strains, including some that emerge decades later.

Researchers analysed blood samples collected in 1994 from adults that had been recently vaccinated against influenza to track how their immune responses fared against influenza strains that circulated over the next 30 years, including influenza A (H1N1, H3N2) and influenza B.

The study, published in Science Translational Medicine, found that the historic vaccine generated broad immune responses against future influenza strains. Antibodies and memory B cells – immune cells that “remember” past infections – were able to recognise future influenza viruses, including H1N1 and influenza B. However, the immune system was not capable of recognising the fast-evolving H3N2 future variants, highlighting why some strains are harder to protect against and why annual vaccination remains important.

The University of Melbourne’s Dr Isabelle Foo, Research Officer in the Kedzierska Laboratory at the Doherty Institute and co-first author on the paper, said the study offers a unique glimpse into how vaccines shape immunity decades into the future.

“We found that the vaccine trained the immune system to spot parts of the virus that don’t change much. Memory B cells preciously kept that information, ready for future encounters,” said Dr Foo.

"This helps explain how vaccination today can protect the body for many years, unless the virus changes significantly, as seen with H3N2, which evolved enough to slip past the immune system.”

The study also revealed differences in immune responses across different age groups.

The University of Melbourne’s Associate Professor Oanh Nguyen, Principal Research Fellow also in the Kedzierska Laboratory at the Doherty Institute, said that while both younger and older adults generated strong vaccine-induced responses, prior exposure influenced how broadly their immune systems could respond.

“We found that, because of lifelong exposure to influenza, older adults, aged 60 to 75, had more mature antibody responses able to recognise a wider range of strains, including the 2009 pandemic H1N1,” said Associate Professor Nguyen.

“However, both age groups mounted strong responses to the vaccine and to some future strains.”

The University of Melbourne’s Professor Katherine Kedzierska, Head of the Human T cell Laboratory at the Doherty Institute, said the study is the first to effectively look back in time to understand future immunity.

“Our study provides rare insights into the breadth of vaccine-induced immunity over 30 years of influenza evolution,” said Professor Kedzierska.

“Influenza vaccines do more than protect against the viruses circulating at the time you’re vaccinated; they can also prepare your immune system to recognise and fight some of the viruses that emerge decades later.

“But gaps remain for rapidly evolving strains like H3N2 and that’s why getting vaccinated every year is so important.

“It also underscores the need for next-generation vaccines that can tackle fast-mutating strains and strengthen pandemic preparedness.

“Our study was made possible by the collaboration of multiple leading laboratories across the Doherty Institute, combining expertise in immunology, virology and vaccine research. I also want to acknowledge Professor Lorena Brown and Dr Georgia Deliyannis who initiated this study back in 1994. I’m incredibly proud of what we’ve achieved together.”

The findings reinforce the importance of yearly influenza vaccination, showing it provides immediate protection while also helping the immune system prepare for future viruses. By identifying which strains are well covered and which are not, the research will help guide the design of improved vaccines to better protect communities against seasonal outbreaks and future pandemics.

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