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Even in the mildest of flu seasons, the most effective flu vaccines remain blunt instruments. Best-case vaccine effectiveness is around 60 percent, and in Australia’s severe 2017 flu season efficacy was much lower.

A study published today in Science Translational Medicine, led by researchers at Melbourne’s Doherty Institute, a joint venture of the University of Melbourne and Royal Melbourne Hospital, analysed samples from people who had the highest immunity from the flu vaccine.

“In the best responders to the flu vaccine, we found that there are three specific types of white blood cells recruited to fight the virus, namely T follicular helper cells, antibody-secreting cells and memory B cells,” says study leader University of Melbourne Professor Katherine Kedzierska.

Why is this important?

“With further work, it may be possible to make a vaccine that recruits or strengthens the response of these specific cells, greatly improving protection for everyone vaccinated. It is also possible that we could predict how well individuals will respond to a particular flu vaccine. This could make a life-saving difference to vulnerable people such as young children, the elderly, Indigenous populations, pregnant women, obese people, or those with underlying health problems,” explains Professor Kedzierska.

The researchers made two further important findings:

1. They found that killer T cells don't respond to current flu vaccines.

One of the study’s lead authors and a University of Melbourne PhD student at the Doherty Institute, researcher Marios Koutsakos explains why this is significant:

“Killer T cells are the ‘ninjas’ of our immune system but the current vaccine does not alert them. If we could make a vaccine that recruits these highly effective virus killers into the flu-fight, we could be much of the way towards the one-shot, one-time, effective flu vaccine that could save hundreds of thousands of lives and a great deal of health care expense and focus.”

2. They identified where in our bodies most of our long-term flu immunological memory B cells reside.

“These memory B cells lurk outside of the blood,” explains Dr Oanh Nguyen, co-leader of the study. “So, if we look only at the blood to inform flu vaccine research – and that’s where most of the research effort has been concentrated until now, we don’t get the full picture – far from it. Potentially, there are long-term flu-fighting resources in under-explored tissues and we think that this is a promising place to look for answers to the very difficult questions that flu asks our immune systems every year.”

* This research was a collaboration between the Doherty Institute (including the Department of Microbiology and Immunology, The University of Melbourne and the WHO Collaborating Centre for Reference and Research on Influenza), Seqirus, Mercy Hospital for Women, St Vincent’s Institute, Alfred Hospital, The University of Sydney and The Garvan Institute.