Researchers say they are one step closer to creating a one-shot influenza vaccine that would give life-long immunity against the virus. Previous research had shown that certain types of T-cells, white blood cells essential in the immune response to flu, can give some people immunity to influenza A viruses - one of three types of flu virus – but how they do this remains unclear.
The international team, led by the University of Melbourne and Monash University, set out to investigate by using single cell technology to hone in on human T-cells one cell at a time to capture their response to different virus strains (PNAS, doi: 10.1073/ pnas.1603106113). T-cell receptors (TCRs) on the T-cells’ surface recognise fragments of antigen proteins on the influenza A virus, triggering the immune system to attack.
However, the researchers found that the TCRs were able to detect and attack new mutant strains of the virus as well as known strains encountered before. Using crystallography techniques at the Australian Synchrotron, they were able to scrutinise the structure of the TCR cells and say it is their flexibility and adaptability that enables them to recognise and defend against the new mutant strains of virus.
‘This is a game changer in flu research,’ claims Katherine Kedzierska of the University of Melbourne, but she cautions further research is necessary before a universal vaccine could be created. ‘Our past research has shown that only a seventh of the world’s population have the tissue make-up that provides universal immunity to influenza, the difference between a runny nose and being bed-ridden. Now we know what to look for, our challenge is to find these receptors in those with a different tissue composition and elicit a similar response.’
This is ‘interesting and new’ work, comments Donna Farber, associate director of the Columbia Center for Translational Immunology (CCTI) in New York. In terms of a universal vaccine, though, Farber warns T cell-mediated protection to influenza is difficult to assess. Unlike antibody-mediated protection, which can prevent illness, T cell mediated protection may limit severe disease or prevent death, but researchers still don’t know how it will affect humans. ‘In mice—they do get ill, but recover faster and are protected from lethal challenge. So, whether the findings are going to change what we know about protection in humans is premature at this point.’
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