Universal vaccine could put an end to all flu

... If only we could develop a vaccine that was effective against all strains of flu, we might prevent both annual epidemics and occasional pandemics like the one now under way.

Recent work suggests it is possible to create just such a vaccine. In fact, the effectiveness of one potential universal vaccine will be tested in people for the first time in September. Could we be on the brink of beating flu?

The reason flu keeps infecting us again and again is that the virus is constantly changing. The first time you get infected, your immune system has to rely initially on innate, non-specific defences. But it also evolves specific defences, learning to make antibodies and immune cells that recognise that particular virus and destroy both it and any cells it has infected. This process can take a week or more, but once we have defences against a virus, we can respond to it much more quickly next time. This is why many viruses, such as measles, make us ill only once.

Flu viruses, however, evolve so fast that this "immune memory" provides only partial protection. Most of the antibodies we produce bind to the globular heads of a surface protein on the virus called haemagglutinin. The next big target is another surface protein, neuraminidase (see "Moving target").

As flu viruses circulate through the human population, some acquire small mutations in haemagglutinin and neuraminidase that alter their shape and prevent our existing antibodies from binding as strongly. If the differences are large enough, we can be infected by one of these new strains, although our symptoms will be milder than if we had no previous immunity to flu at all.

And so it goes on. By staying one step ahead of our immune systems, the flu virus can infect large numbers of people year after year. What's more, every few decades a flu strain acquires a new haemagglutinin - by swapping genes with a pig or bird flu strain, say - that is very different from those most people have immunity to, so we have very little protection. This is when flu goes pandemic.

Existing flu vaccines all work by mimicking natural infections. Based on global monitoring of flu strains, virologists try to predict which haemagglutinin and neuraminidase will dominate during the next flu season. The annual vaccines contain inactivated flu viruses bearing these specific proteins. If the virologists guess right, the vaccine will protect you until the virus changes enough again.

There is, however, a flaw in the whole idea of producing vaccines that mimic natural infections. "Haemagglutinin's a decoy," says Wayne Marasco, an immunologist at Harvard Medical School in Boston. "Those globular heads can undergo many mutations without the virus suffering any ill effects." ...

To refocus the immune attack, the idea is to create vaccines containing only the conserved proteins, rather than whole viruses. Most attention has focused on the M2 protein, an ion channel that protrudes from the virus's surface and tells it when it is inside a cell. M2 also appears in abundance in the membrane of cells producing new flu viruses, so targeting it with antibodies will lead to the destruction of infected cells as well as the virus itself. ...

via Universal vaccine could put an end to all flu - health - 21 August 2009 - New Scientist.