Saturday, July 9, 2011

Universal Flu Vaccine A Step Closer

Annually changing flu vaccines may soon lead to a single, universal flu vaccine according to a new report from scientists at The Scripps research Institute and the Dutch biopharmaceutical company Crucell. They explain an antibody tested on animals, that can prevent and possibly cure infections within a broad spectrum of influenza viruses, including some seasonal and potentially pandemic strains.

The finding shows the influenza subtypes neutralized with the new antibody include H3N2, which killed an estimated 1 million people in Asia in the late 1960s. This antibody, and the one reported in 2009 have the potential to protect people against most influenza viruses.

Ian Wilson, the Hansen Professor of Structural Biology and a member of the Skaggs Institute for Chemical Biology at Scripps Research, has been working with Crucell scientists to help overcome the problem with current influenza vaccines, which is that they work only against the fe strains that the vaccine makers predict will dominate in a given year, making their effectiveness temporary. In addition, current influenza vaccines provide little or no protection against unforeseen strains.

These problems reflect a basic flu-virus defense mechanism. The viruses come packaged in spherical or filamentous envelopes that are studded with mushroom-shaped hemagglutinin (HA) proteins. These outer structures effectively serve as decoys for a normal antibody response. The outer loops on the HA head seem to attract most of the antibodies, but in a certain strain these loops can mutate to evade an antibody response within months. Antiviral drugs aimed at these and other viral targets also lose effectiveness as flu virus populations evolve. The goal of the research is to find and attack relatively consistent and functionally important structures on flu viruses.

By sifting through the blood of people who have been immunized with flu vaccines, researchers discovered an antibody that bound to one such exposed structure. In mice, an injection of the antibody could prevent or even cure a lethal infection by about half of flu viruses, including H1 viruses such as H1N1, which caused deadly global pandemics in 1918 and 2009.

Researchers determined the 3D molecular structure of CR6261 and its binding site on HA. The binding site turned out to be on HA’s lower, less-reachable stalk portion. The bind of CR6261 to that region interferes with flu viruses’ ability to deliver their genetic material into host cells and start a new infection.

Crucell researchers searched for an antibody that could neutralize some of the remaining flu viruses unaffected by CR6261, and recently found one called CR8020. CR8020 powerfully neutralizes a range of human-affected flu viruses in lab-dish tests and in mice. The affected viruses include H3 and H7, which have already caused pandemic or sporadic human infections.

Crucell is about to begin initial clinical trials of CR6261 in human volunteers, and the company expects to begin similar trials of CR8020. If those trials succeed, the two antibodies could be combined and used in a passive immunotherapy approach. This would mainly be useful as a fast acting therapy against epidemic or pandemic influenza viruses. The ultimate goal is an active vaccine.


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