Identification of shared regions of flu viruses provide the solution to an elusive universal vaccine

Monash BDI's Professor Anthony Purcell.
Monash BDI's Professor Anthony Purcell.

Researchers from Monash University and the Peter Doherty Institute for Infection and Immunity (Doherty Institute) have identified immune cells, called killer T cells that can fight all influenza viruses – A, B and C  – creating the potential for the development of a world-first universal, one-shot flu vaccine.

The extraordinary breakthrough made by University of Melbourne PhD student, Marios Koutsakos of the Doherty Institute, was published today in Nature Immunology and is a paradigm-shifting discovery, which could lead to an influenza vaccine that does not need to be updated annually.

Previous research has shown that these killer T cells are present in an immune response to some but not all the influenza viruses – making this discovery a game-changer in the development of a universal vaccine.

“Influenza viruses continuously mutate to evade recognition by our immune system, and they are vastly diverse, making it nearly impossible to predict and vaccinate against the strain that will cause the next influenza pandemic,” Mr Koutsakos said.

“We have identified the parts of the virus that are shared across all flu strains, and sub-strains capable of infecting humans, and then investigated if we could find robust responses to those viral parts in healthy humans, and influenza-infected adults and children.”

The research team worked with cutting-edge technology in collaboration with Professor Anthony Purcell from the Monash Biomedicine Discovery Institute, to identify these common viral targets for killer T cells.

The Purcell laboratory is at the forefront of epitope discovery using mass spectrometry.1

“It has been particularly beneficial to combine our expertise with the influenza team at the Doherty Institute, to help map cross-strain reactive epitopes. This work highlights the underlying power and versatility of the mass spectrometry approach, and we are excited about the future potential of these epitopes in the development of universal vaccines,” Professor Purcell, co-corresponding author on the paper, said.

University of Melbourne Professor Katherine Kedzierska, co-corresponding author and laboratory head at the Doherty Institute, said this was an exciting discovery that clearly revealed killer T cells provide unprecedented immunity across all flu viruses, a key component of a potential universal vaccine.

“Influenza B immunology particularly has remained largely understudied because it doesn’t have pandemic potential. However, it is a serious virus that can lead to death and severe illness, mostly in children, and was one of the missing pieces of the universal flu protection puzzle,” Professor Kedzierska said.

The team now has a patent on the discoveries, which will enable them to develop a universal influenza vaccine approach to reduce the impact of pandemic and seasonal influenza around the world.

In addition to the experiments of the human immune system to prove the killer T cell commonality across all flu strains, something that has never been done before, the research team conducted vaccination tests to demonstrate the protective capacity of killer T cells.

“Our immunisation studies with the peptide responsible for activating the killer T cells revealed remarkably reduced levels of flu virus and inflammation in the airways,” Mr Koutsakos said.

These killer T cells are found in over half the world’s population. Professor Kedzierska’s group is now researching immunity in high-risk ethnic groups including Indigenous Australians and Indigenous Alaskans who might not share the same immune response as those investigated by this project.

“Now this groundwork has been done, we can apply similar technologies and approaches to those high-risk populations that flu has a huge impact on, so we can offer protection to everyone,” Professor Kedzierska said.

This research was an International collaboration between scientists at Monash University; the Doherty Institute at the University of Melbourne; the WHO Collaborating Centre on Influenza; St Jude Children’s Research Hospital, Memphis; Seqirus; St Vincent’s Institute; The Alfred Hospital; the Royal Melbourne Hospital; University of New South Wales; and the Garvan Institute.

Read the full paper in Nature Immunology titled Human CD8+ T cell cross-reactivity across influenza A, B and C viruses.

1 Mass spectrometry is the very sensitive measurement of the mass and structural characteristics of small biological molecules including the peptides that define T cell epitopes.

About the Monash Biomedicine Discovery Institute 
Committed to making the discoveries that will relieve the future burden of disease, the newly established Monash Biomedicine Discovery Institute at Monash University brings together more than 120 internationally-renowned research teams. Our researchers are supported by world-class technology and infrastructure, and partner with industry, clinicians and researchers internationally to enhance lives through discovery.