Antibody Targets Multiple Flu Strains With Long Protein Fingers

Fall brings many lovely things - falling leaves, pumpkin-spiced lattes - but also some unpleasant things, like influenza.

Influenza is a tricky disease to combat, because it's not just a single illness, but more like an entire family of afflictions. Drugs and vaccines that target one strain may not work on another due to small mutations between two kinds of flu. Still, scientists dream of universal vaccines and universal therapies that could throttle pandemics before they even have a chance to spread.

Now, a recent paper in Nature describes an antibody that can target many subtypes of influenza at once.

Scientists from the Scripps Research Institute and Sea Lane Biotechnologies worked together to isolate and describe the structure of the antibody, called C05. C05 can recognize and attach to a region on the outer coat of the virus called the receptor binding site, or RBS. When the antibody binds to this region, it blocks the virus's ability to attach to a host cell.

Best of all, the RBS seems to be a fairly standardized part amongst influenza A strains, including H1, H2, H3 and H9 subtypes.

It covers all the pandemic strains in humans, senior author and Scripps researcher Ian Wilson said in a phone interview.

Previously, scientists hadn't thought that an antibody could dock at such a small binding site.

But C05, which Sea Lane isolated from a huge library of antibodies generated by people exposed to various kinds of flu, has a special kind of structure. Antibodies latch onto their targets using two arms, which are each equipped with six protein fingers shaped like loops. Usually an antibody fixes itself on a target by bear-hugging it and the surrounding structures, which can vary between strains.

C05, however, has one single protein loop on each arm that is elongated.

This enables it to poke into the site without touching the rest of the binding site, Wilson explains.

This 'one-finger grip' is what allows C05 to latch onto so many different influenza strains. It also appears that C05 works best when it is grabbing onto two RBSs with both of its long protein fingers, according to Wilson.

In lab experiments, C05 warded influenza A viruses away from cells in Petri dishes. When the antibody was administered to mice, it protected them against the flu even when the animals were exposed to lethal flu doses. C05 also worked as a therapy for mice already infected with influenza.

But characterizing the antibody is just the first step. To even begin to develop a vaccine that exploits C05's nimble fingers, scientists will have to develop a component that will mimic the viral RBS, in order to provoke a patient's immune system into creating antibodies against it. There is also the possibility that doctors could administer antibodies directly to patients to treat or prevent influenza.

SOURCE: Ekiert et al. Cross-neutralization of influenza A viruses mediated by a single antibody loop. Nature published online 16 September 2012.