In 2013, an elderly man in China fell ill after catching a virus from a live chicken his wife had asked him to buy at a local market. He was patient zero in the first outbreak of a new strain of avian flu called A (H7N9) that killed over 30% of humans infected and hospitalized 99% of survivors.
Since the first cases were reported in March 2013, 640 people have become infected and 224 have died from A (H7N9) globally through March 2015 - most from the mainland of China. The virus passes from infected birds to humans.
As that first outbreak ensued, Australian and Chinese scientists teamed up to investigate why some people died while others survived, and why some survivors recovered more quickly than others.
The researchers found the clue lay in the way a certain group of white blood cells - called CD8+ T cells - responded to the new virus.
They believe their discovery could advance flu vaccine technology and bring closer the day when people just have one flu jab that protects them for life.
One of the investigators, Katherine Kedzierska, an associate professor at the University of Melbourne in Australia, explains how the team - which included specialists from Melbourne and virologists from Fudan University in Shanghai, China - reacted to the outbreak:
"We'd never seen anything like H7N9. The virus was infecting more people rapidly and nobody had immunity. Thankfully, we did manage to contain the virus but we knew we had come face-to-face with a potential pandemic that could kill millions of people around the world if the virus became able to spread between humans."
Early, virus-specific CD8+ T cell response was key to faster recovery in survivors
CD8+ T cells are the body's "assassins" when it comes to taking out new viruses - they kill cells infected with the virus. The new study - published in Nature Communications - explains how these cells memorize the viruses.
When the immune system is faced with a new virus, a cascade of defenses kicks in, involving different groups of cells at different times. First, the innate immune system responds with some generalized defenses to try and stop the virus multiplying and spreading.
This is followed by the adaptive immune response that specifically targets the virus and, if all goes well, clears it from the body.
The speed and pattern of the immune response, particularly how quickly and precisely it targets the new virus, is a big factor in how well it succeeds in overcoming the pathogen.
In the case of the 2013 Chinese A (H7N9) outbreak, the Australian and Chinese team found patients who recovered quickly showed evidence of early CD8+ T cell responses that were specific to the new virus.
The patients that took longer to recover showed a similar - but delayed - CD8+ T cell response, coupled with late recruitment of CD4+ T cells and antibodies that was later boosted by another group of NK cells.
But in the patients who died, the researchers found little evidence of immune cell response that was specific to A (H7N9), and no sign of any T cell activation.
"After collecting samples from infected patients we found that people who couldn't make these T cell flu assassins were dying," Prof. Kedzierska notes.
Step closer to 'one-off universal flu vaccine shot'
The researchers concluded that it was the ability of flu-killing CD8+ T cells to memorize distinct strains that protected the patients who recovered most quickly from being severely affected by the new influenza A virus.
The team believes their discovery could lead to new cellular memory-implant technologies that help flu vaccine developers move from targeting specific flu strains toward a universal one that is based on T cells. Prof. Kedzierska concludes:
"Our extraordinary breakthrough could lead to the development of a vaccine component that can protect against all new influenza viruses, with the potential for future development of a one-off universal flu vaccine shot."
She says their findings should also help doctors predict how well their patients' immune systems are likely to respond to viruses so they can intervene early with artificial ventilation and other treatments, especially if patients are at risk of dying.
In October 2014, Medical News Today learned how another research group led by Brown University in Providence, RI, showed that once CD8+ T cells tackle one virus, they will fight others.
In that study, the team challenged the traditional view that CD8+ T cells can only deal with one pathogen. They discovered that once CD8+ T cells fight one pathogen, they join the innate immune system, ready to respond to cytokine signals that are set off by a wide variety of infections.