Researchers are one step closer to creating a universal, one-shot influenza vaccine following the discovery that T cells, essential in the immune response to influenza, can recognise and attack emerging, mutant strains of the virus.
An international research collaboration, led by University of Melbourne Associate Professor Katherine Kedzierska from the Peter Doherty Institute for Infection and Immunity and Dr Stephanie Gras from Monash University, used cutting edge single-cell technology, never before used in human influenza investigations, to hone in on human T cells one cell at a time to capture their response to the various strains.
The study, published in Proceedings of the National Academy of Sciences (PNAS) on Monday, found how the T cells reacted to new mutant strains of influenza as well as viruses they had previously been exposed to.
The team used the Australian Synchrotron to scrutinise the structure of the cells to identify how they recognise the mutant strains. They found that it was their flexibility and ability to adapt that enabled the T cells to essentially bully the new strains into submission.
Associate Professor Kedzierska said finding this piece of the puzzle was a major step forward on the path to creating a one-shot, T cell-mediated influenza vaccine for life-long immunity against the virus, which the World Health Organization estimates infects between three and five million people globally every year.
‘This is a game changer in flu research. Previous research has shown us T cells provide universal, protective immunity to influenza but, until now, we didn’t know why or how.
‘By using state-of-the-art procedures, this study enabled us to dissect the immune response to understand how this immunity occurs.’
Associate Professor Kedzierska said further research was 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.’
Dr Stephanie Gras said the precise, high-power X-Ray capability of the Macromolecular and Micro Crystallography (MX1 and MX2) beamlines was essential to the four-year study.
‘Use of the Australian Synchrotron was absolutely crucial to understanding these fine details of the immune response to influenza.’
Above image courtesy of ABC news
- ‘Australian flu research raises hopes for universally effective vaccine’, on ABC’s PM, Wednesday 30 March 2016
On Wednesday 9 March, the Minister for Industry, Innovation and Science, the Hon. Christopher Pyne MP, visited the Australian Synchrotron, touring the facility floor before announcing the Australian Government's agreement to the facility’s transfer to the Australian Nuclear Science and Technology Organisation (ANSTO).
While visiting the Micro Crystallography (MX2) beamline Mr Pyne was updated on a new anti-leukaemia drug developed in Australia thanks to the combination of a world-class medical research institute, the best and brightest researchers and access to the Australian Synchrotron’s landmark infrastructure, and partnership with industry, ensuring Australian public hospital patients were the first in the world to access this novel therapy.
Concerns have been raised over the long-term use of nutritional supplements containing chromium, after an Australian research team found the supplement is partially converted into a carcinogenic form when it enters human cells.
Chromium is a trace mineral found primarily in two forms: a range of chromium(III) forms are sold as nutritional supplements, while hexavalent chromium(VI) is its ‘carcinogenic cousin’, gaining notoriety from the book and 2000 movie, Erin Brockovich, which linked a cluster of illnesses to its presence in drinking water. Controversy remains over whether the dietary form of chromium is essential, with an increasing body of evidence indicating it is not safe.
In the study, researchers from The University of Sydney and UNSW treated cells with chromium(III) before creating a map of every chemical element contained inside the cell using an intense synchrotron X-Ray beam at the Advanced Photon Source (APS) in Chicago. The team accessed the APS through the Federal Government’s Australian Synchrotron Research Program, which provided researchers with synchrotron access prior to the Australian Synchrotron opening in 2007.
Dr Lindsay Wu, from UNSW’s School of Medical Sciences and who originated the research while at The University of Sydney, said the high energy synchrotron beam allowed the team to identify and classify chromium spots throughout the cell.
‘The powerful X-Ray enabled us to determine whether the spots were chromium(III) or a combination of chromium(III), chromium(V) and chromium(VI).
‘The health hazards associated with exposure to chromium are dependent on its oxidation state – we were able to show oxidation of chromium inside the cell does occur, meaning it loses electrons and transforms into a carcinogenic forms, which no-one had been able to do in a biological sample before.’
Supplements containing chromium are consumed for the purported treatment of metabolic disorders, such as insulin resistance and type 2 diabetes, but chromium’s mechanism of action in the body is not well understood.
These supplements are also commonly used for weight loss and body building with some containing up to 500 micrograms per tablet, above the 200 micrograms estimated as a safe and adequate daily dietary intake for adults by the US National Academy of Sciences. Australia’s current National Health and Medical Research Council Nutrient Reference Values, which are currently under review, recommend 25-35 micrograms of chromium daily as an adequate intake for adults.
Research lead Professor Peter Lay from the University of Sydney’s School of Chemistry said with the latency period for chromium(VI)-related cancers often greater than 20 years, the finding raises concerns over the possible cancer-causing qualities of chromium compounds and the risks of taking chromium nutritional supplements long term or in high doses.
‘With questionable evidence over the effectiveness of chromium as a dietary supplement, these findings should make people think twice about taking supplements containing large doses of chromium.
‘However additional epidemiological research is needed to ascertain whether chromium supplements significantly alter cancer risk, since long-term laboratory experiments have not been conducted under the conditions of high oxidative stress (which promotes chromium(III) oxidation) associated with diabetes.’
The researchers said the findings are very unlikely to apply to trace amounts of chromium(III) found in food.
Experiments were also conducted at the former Australian National Beamline Facility at the Photon Factory in Japan, operated by the Australian Synchrotron, which helped clarify the nature of the chromium(V) and chromium(VI) species formed in the cells, both of which can cause cancer.
The research, published in the prestigious chemistry journal, Angewandte Chemie was also supported by the Australian Research Council.
Originally published by UNSW Media.
‘Popular chromium supplements linked to carcinogens’, Sydney Morning Herald, Monday 11 January 2016.