Melbourne researchers have revealed why flu vaccines work better in some people and not others.

Australian scientists have discovered three specific white blood cells which play a key role in determining whether a person responds well to flu vaccines, a breakthrough that could lead to better protection against future deadly strains of the virus.

Best-case vaccine effectiveness is around 60 per cent, however efficacy was much lower during the 2017 flu season.

A study led by researchers at Melbourne's Doherty Institute and University of Melbourne analysed blood samples taken from healthy people who got the flu shot in 2014, 2015 and 2016.

It was found in the best responders to the flu vaccine there were three specific types of white blood cells recruited by the immune system to fight the virus. These were T follicular helper cells, antibody-secreting cells and memory B cells.

The "exciting" discovery has raised hope of significantly more effective vaccines.

"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," said study leader University of Melbourne Professor Katherine Kedzierska.

Last year's flu season swept across Australia a month earlier than usual, and after the peak had claimed nearly 600 mostly elderly lives.

A fast-mutating and evolving strain of influenza A - H3N2 - defied efforts to stop its spread and was blamed for the majority of deaths.

By December, there had been 234,869 laboratory-confirmed notifications of influenza in Australia for 2017, more than two-and-a-half times the number compared with the previous season.

The majority of deaths reported to the National Notifiable Diseases Surveillance System (NNDSS) were due to influenza A.

Importantly, the new research published on Thursday in Science Translational Medicine, also found that killer T cells did not respond to current flu vaccines.

According to Professor Kedzierska, this may mark an important step towards the development of a 'one-shot' vaccine that would do away with the annual flu shot.

"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," she said.