19 Feb 2019
‘Killer’ immune cells provide solution to elusive universal flu vaccine
Researchers from the Peter Doherty Institute for Infection and Immunity (Doherty Institute) and Monash University 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.”
University of Melbourne Professor Katherine Kedzierska, study leader 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.
Mr Koutsakos and his colleagues in Professor Kedzierska’s laboratory at the Doherty Institute 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. 
“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 said.
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 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, the Royal Melbourne Hospital), with scientists from Monash University; 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 Garvan Institute.
 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.
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