Research points to new antiviral drugs and universal influenza vaccines

Researchers at The Scripps Research Institute in La Jolla, California, supported in part by the National Institutes of Health, have identified a common Achilles' heel in a wide range of seasonal and pandemic influenza A viruses.

The study found an infection-fighting protein, or human antibody, that neutralizes various influenza A virus subtypes by attaching to these viruses in the same place. This common attachment site provides a constant region of the flu virus for scientists to target in an effort to develop a so-called universal flu vaccine. Such a vaccine would overcome the annual struggle to make the seasonal flu vaccine match next year's circulating flu strains and might help blunt emerging pandemic influenza viruses as well.

The study provides data about the antibody attachment site that are similar to the findings of another research group, reported on February 22, 2009 (see http://www3.niaid.nih.gov/news/newsreleases/2009/flu_mab.htm). Taken together, these studies provide a blueprint for efforts to develop new antiviral drugs as well as a potential universal influenza vaccine.

The Scripps research team, led by Ian A. Wilson, Ph.D., in collaboration with researchers at the biopharmaceutical company Crucell Holland (The Netherlands), discovered the potent antibody during a systematic examination of blood samples taken from healthy individuals who previously had been vaccinated with the ordinary seasonal flu vaccine. Using sophisticated screening technologies, the scientific team isolated antibodies that recognize flu viruses to which the average person has never been exposed, such as H5N1 avian flu viruses. Through this process, the scientists found one antibody called CR6261 that had broad neutralizing capabilities. Subsequently, they found several antibodies similar to CR6261 in other donors as well. With the help of a robotic crystallization laboratory, the Scripps team quickly determined the detailed three-dimensional structures of this antibody when bound to the H1 virus that caused the 1918 pandemic flu as well as to an H5 virus with pandemic potential. CR6261 bound to a relatively hidden part in the stem below the mushroom-shaped head of the hemagglutinin protein, one of two major surface proteins found on the flu virus.