Killer T cells may hold key to permanent flu vaccine

A new approach to a shot that could stop recipients ever getting sick from the virus again.

In early 2009, a mutant form of the H1N1 flu virus that is endemic in pigs began spreading rapidly through the human population. Ajit Lalvani, an immunologist at Imperial College, London, had been waiting for such an event. He planned to make this the last deadly flu pandemic that the world ever saw.

Lalvani wanted to use the pandemic as a giant natural experiment. He and his team would compare the immune systems of people who got sick and those who did not. Tracking the difference would point the way to a new type of flu vaccine, he hoped.

Current seasonal vaccines trigger the immune system to make antibodies. These recognise the unique structure of the surface of the virus. But flu viruses constantly change, or mutate, and evade antibodies. If a completely new lethal strain suddenly emerges, swathes of the population might die before production of the necessary new vaccine can ramp up.

So Lalvani looked to another part of the immune system to do a better and more durable job. He hoped that so-called killer T cells would form the basis of a universal vaccine that stays on target even as the flu virus changes.

Flu researchers have been thinking about T cells since the 1990s, when experiments on infected people suggested that certain killer T cells were the first-line defence against the flu virus. These cells appeared to hold the virus at bay until the body built up specific antibodies to the virus.

Perhaps having higher levels of killer T cells could help the immune system fight a new strain of killer virus.

The 2009 swine flu epidemic provided Lalvani and his team with the conditions to put that theory to the test. As a new form of flu, they could be sure nobody had protective antibodies against it, so infected individuals would initially rely on their T cells alone.

The researchers recruited a sample population of 342 healthy students and staff at Imperial College and monitored their progress during the pandemic. Each person donated a blood sample and was given a packet of nasal swabs. Every three weeks they had to report back on their health. If they experienced flu symptoms they took a nasal swab and sent it in to the lab.

The results of the study, published in September in Nature Medicine, confirmed the theory: the more of one particular sub-group of killer T cells that a person had, the less sick they got from the flu. Some people had such a strong population of these cells that they experienced no symptoms at all from catching the bug.

“This result is really good news,” says Arno Mullbacher, a universal flu vaccine researcher based at the Australian National University in Canberra.

Now a universal vaccine might not be far away. Lalvani’s study didn’t just reveal the type of killer T cells that were protective, he discovered the recipe for making them; in other words, a vaccine.

The team established the particular bits of the virus that these cells were recognising and responding to. “Now, we can just get on and develop the vaccine and do the clinical trials,” says Lalvani. That process should take less than five years, he says. Flu researchers such as Mullbacher are enthused at the prospect of a truly universal vaccine: “If you gave people this vaccine and then a new bird flu emerged, they would not die, and they would have time to develop an antibody.”

Lalvani’s study also has some controversial implications. It adds weight to recent suggestions that getting a seasonal flu shot every year might compromise your long-term resistance. If, by always being vaccinated, you never actually catch the flu, then your population of virus-recognising T cells would never be stimulated to expand, potentially leaving you vulnerable in the event of a new pandemic. But the idea is far from proven, and the official advice remains that at-risk individuals, such as those over 65 years of age, should get the flu jab ever year.

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