Harnessing the power of natural immunity to extend vaccine protection

Up to 650,000 people die of respiratory diseases linked to seasonal influenza (flu) worldwide each year.¹

Currently an annual vaccination is the best way to prevent influenza.

This story is part of our 10 of the Best - fourteenth edition. 10 of the Best is an annual NHMRC publication, showcasing 10 NHMRC-funded health and medical research projects. See more 10 of the Best.

'We want to make a flu vaccine that you get once a decade, rather than once a year,' Associate Professor Wakim says.

Influenza vaccines typically stimulate the production of antibodies that attach to outer structures and disable the virus. These antibodies provide short-term protection from viruses with the same outer structure.

Unfortunately, the outer structures of viruses are constantly changing, so a new vaccine is needed each year to target those structures on the circulating influenza strains.

Vaccines stimulating the development of T-cells, a type of white blood cell that fights infections, are likely to offer longer lasting immunity. Whilst antibodies are good at recognising the proteins on the outside of a virus, T-cells can recognise invariant proteins on the inside of the virus.

'These cells are long lived and respond to highly conserved components of the influenza virus, as such, they can provide long term protection against a wide breadth of influenza virus strains,' Associate Professor Wakim says.

Along with a team of collaborators, Associate Professor Wakim found that by lodging memory T-cells in the upper respiratory tract, they blocked an inhaled influenza virus from reaching the lung, ultimately preventing the development of severe pulmonary disease.²

The team found key requirements for T-cells to lodge in the upper respiratory tract. Using this knowledge, they developed a proof-of-concept intranasal vaccine candidate, delivered through a nasal spray, and designed to specifically encourage resident memory T-cell development.  

'We are now in a position where we can leverage the knowledge we have gained from the many years of performing basic research to design new and improved influenza vaccines, which will save lives, reduce health care costs, and reduce lost economic productivity,' Associate Professor Wakim says.

'It is very satisfying when, after years researching a specific question, all the pieces finally fit together.'

After undertaking postdoctoral research at the University of Washington in Seattle, USA, Associate Professor Wakim returned to Australia to continue her research, to find the only virus the laboratory had in the freezer was influenza.

'[This] turned out to be the perfect model pathogen for me to continue this research,' she says.

Next Steps

The research team is aiming to develop a novel 'one-shot’ intranasal influenza vaccine that provides long term, cross strain protection against seasonal and newly emerging pandemic strains. The technology will lodge influenza reactive resident memory T-cells along the respiratory tract.

Associate Professor Wakim says the team are currently optimising formulations and hope to test these candidates in vivo within the next 12 months, ultimately translating the findings from the basic research project to development of an intranasal influenza vaccine candidate.