Flu vaccination for all is the cure

by stevechasmar

NIAID scientists propose new explanation for flu virus antigenic drift

[Via EurekAlert! – Infectious and Emerging Diseases]

(NIH/National Institute of Allergy and Infectious Diseases) Influenza viruses evade infection-fighting antibodies by constantly changing the shape of their major surface protein. Now, researchers from NIH/National Institute of Allergy and Infectious Diseases have proposed a new explanation for the evolutionary forces that drive antigenic drift.

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Pretty cool little experiment here. Using a mouse model, they showed that the response of the flu virus to people already immunized against it was to increase the binding of one of its coat proteins to a receptor found on human cells. By doing this, it shielded this protein from the very antibodies that had been developed to neutralize the virus.

Evolution in action.

But if the virus produced mutants that bound too tightly, it was rendered less infective. The virus gets stuck to cells in the nose and never makes it to the lungs. Wonderful

What was really interesting was that when these mutated viruses were put into naive mice that had no antibodies to the virus, the virus tended to revert back to normal binding activity and the virus bound the receptor with a low affinity.

It usually did this by making new mutations in other areas of the protein involved in binding to cells. But because the viruses retained the original mutations, they still retained a greater ability to evade antibodies than the original flu viruses.

From their paper:

  

The blue shows the cell binding ability in each round while the red represents the ability to evade detection by the immune system.

What they found was that each round of pressure-release generated sets of mutations that altered the affinity for the receptor and that also resulted in escape from antibody recognition. When pressure was released, new mutations occurred that reduced the receptor binding back to normal. But the ability of these new forms of the virus to escape detection from antibodies remained higher than before.

SInce each round tended to result in different mutations, the cumulative effects after several rounds were to have a virus which was substantially able to escape antibody detection, even in immunized humans. eventually enough mutations would accumulate for the virus to completely evade the immune system, even in vaccinated humans.

The authors postulate that this is a major cause for antigenic drift, the small changes that are seen in the flu virus from season to season. Moving from selective pressure in vaccinated humans to unselected naive humans and back again creates a push me-pull you effect, driving rapid change in the virus.

This drift would be what causes new forms of flu to be seen each year. This process increases the chances that new mutations will occur that escape antibody detection, resulting in a new seasonal flu outbreak.

Putting organisms under selective pressure, then removing that pressure, then reapplying it has been shown to drive very rapid genetic changes. This often results in mutants that can elude the selective pressure. This is often why antibiotics fail when they are not used properly. It is the iterative process of pressure, release, pressure, release that can often create mutants that evade whatever the selective pressure is, such as our immune system.

The key to preventing this would then be to come up with a way to prevent the release of the selective pressure being applied by the immune system. The pressure needs to constantly be applied.

The authors suggest that increasing herd immunity by increasing the vaccination of the major pools for the virus, such as children, will provide the virus with fewer places to revert and mutate. This would keep the pressure up enough to prevent the sorts of antigenic shift that we see.

The virus would then be under continuing pressure to stick really strongly to the receptor and maybe never make it to the lungs at all. At least this would greatly reduce the ability for antigenic drift to occur, reducing the need to come up with new seasonal vaccines each year.

It is a nice hypothesis. It implies that greater vaccination would reduce the drift we see each year, making it less likely that the seasonal outbreaks would keep occurring. Thus we would only have to get one (or a few) vaccinations in our lifetimes. Until an antigenic shift occurred and we needed a new vaccine.