Twin attack could deliver universal flu vaccine

A UNIVERSAL vaccine. It is the stuff of dreams for flu scientists, but it could be within reach if a new type of vaccine that elicits an immune response from white blood cells is combined with traditional vaccines.

Every year, between 250,000 and 500,000 people of all ages die worldwide after getting seasonal flu, partly because few people are vaccinated for it. When a novel human flu evolves in pigs or poultry and becomes pandemic, the numbers can be even higher. The solution is better vaccines for people and animals.

Flu comes back every year because when you catch it or are vaccinated, your immune system is only trained to identify the flu's large surface proteins. These proteins change from year to year, allowing flu to strike again if you haven't had an updated vaccine.

To end the need for continually updated shots, researchers have tried to create a vaccine for all flu, with varied success.

Most attempts have been vaccines designed to make us produce antibodies, aimed not at flu's surface proteins, but at internal proteins that are the same in all flu viruses. Success has been mixed. But there is another arm to the immune system. White blood cells called T-cells tend to attack a wider range of invaders than antibodies. If a vaccine sensitises them to internal flu proteins, they could potentially kill all types of flu.

Earlier this year, Sarah Gilbert and colleagues at the University of Oxford equipped the virus used in the smallpox vaccine, which stimulates this cell-mediated immunity, with two proteins common to all flu viruses. They reported that this vaccine prevented symptoms in some people experimentally infected with flu, and those that did get sick had milder symptoms.

Now Colin Butter and colleagues at the Institute for Animal Health in Compton, UK, have tested that vaccine, and a similar one made of a different live virus, in chickens (Vaccine, doi.org/jz6). Just as in people, it did not prevent infection, but the birds' T-cells responded strongly, and less of the virus was passed on.

Neither result sounds very impressive. But, says Butter, the key will be combining these vaccines with the classic kind that elicits antibodies. Gilbert reports that her team has tested such a combination in people, and has seen cell-mediated immunity to the universal proteins, as well as antibodies to specific surface proteins.

Such a combination could be more than the sum of its parts. In chickens, for example, antibodies could knock out the main virus, while T-cells mop up the variants that evade the antibodies and allow the virus to keep spreading - and evolving. "We could finally get vaccines that stop viral spread completely," says Butter.

The "universal" proteins would also give chickens and humans some protection against novel flu viruses. And because they work against all flu, such vaccines can be stockpiled to prepare for pandemics. "I'd love to have a stockpile of vaccine with both antibody and cell-mediated capabilities," says Thomas Reichert of the Entropy Research Institute in Lincoln, Massachusetts. This gives us a chance to beat an adversary we've been defeated by time and again. Or as Reichert puts it: "Now that might bring flu to the negotiating table."

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