An extraordinary breakthrough in influenza research moves us closer to the development of a vaccine that can protect against all new influenza viruses, with the potential of developing a one-off universal flu shot.
The research led by the University of Melbourne, in conjunction with Fudan University in China, investigated the immunity response of patients to the first outbreak of the avian-derived H7N9 influenza virus that emerged in China in 2013.
Research into the H7N9 influenza strain provides new insights into how the mechanism of the immune system responds to an alien influenza virus and how the disease progresses. The findings identify the ‘killer’ CD8+ T cells as providing optimal protection against the influenza virus.
“This deadly avian-derived H7N9 influenza virus is contracted from birds and began with people buying chickens in marketplaces,” says Associate Professor Kedzierska from the University of Melbourne.
“Currently people contract the virus from birds, however if the virus starts to spread from human to human, it has the potential to become a world pandemic and kill millions of people.”
In the people who were hospitalised at the Shanghai Public Health Clinical Centre, the flu virus caused severe acute respiratory illness, resulting in 99 per cent hospitalisation rates and greater than 35 per cent mortality rates.
“Current annual vaccines, which are based on antibodies, are the best way to combat the known seasonal influenza strains which mutate rapidly,” Associate Professor Kedzierska says.
“However, when a new virus emerges it’s our immune system that must fight the virus in the absence of a vaccine.”
“We questioned what components of the immune system drive recovery from this severe H7N9 disease and found that recovery is driven by a diversity of immune system components, dominated by an early presence of the ‘killer’ CD8+ T cells.”
The findings show, for the first time, that the nature of the immune system’s mechanism influences the length and outcome of human influenza disease.
“Patients who recovered – most within 2-3 weeks – had the robust ‘killer’ CD8+T cell responses, whereas those who died had a diminished presence of the ‘killer’ CD8+T cells,” Associate Professor Kedzierska says.
These findings lead to the potential of moving from vaccines for specific influenza strains toward developing a vaccine component, which is based on T-cells, and the optimal immune responses witnessed in the patients who recovered quickest in the study.
This will also assist clinicians to make early predictions of how well a patient’s immune system will respond to viruses so they can manage early interventions more effectively, particularly in cases where the patient is at risk of dying.
Associate Professor Kedzierska explains that ‘killer’ T cells target an interior ‘conserved’ part of the virus which does not change when the virus mutates and the ‘killer’ T cells maintain memory of these exposures. When they recognise these same ‘conserved’ parts in a new virus, they recognise the ‘conserved’ parts and kill the early infection.
“After spending the past 40 years working on the virus-specific ‘killer’ T cells, this is the first study from our group that shows their role in protecting people against a new human influenza A virus,” says Nobel Laureate Professor Peter Doherty, one of the lead authors of the study from the University of Melbourne.
Co-author, Professor Xu said the study will significantly enlighten T-cell based vaccine development and immune intervention during severe influenza infection in the future.
“This international collaboration between the University of Melbourne and Fudan University has brought together the immunological expertise in Melbourne and the clinical knowledge in Shanghai to produce a study of much higher impact than could be achieved individually,” says head of the University of Melbourne’s Department of Microbiology and Immunology Professor Elizabeth Hartland, “and it exemplifies the approach we are taking at the Peter Doherty Institute for Infection and Immunity.”
Source: The Age