Getting better: Flu vaccines might be improved Credit: istockphoto

To keep pace with rapidly mutating flu viruses, scientists reformulate influenza vaccines annually. In the process, they must accurately predict which strains will circulate each flu season. Now, new research suggests that scientists might be able to design a more potent vaccine that can deliver immunity to multiple flu strains.

Previously, researchers had identified antibodies that neutralize multiple influenza virus strains (Proc. Natl. Acad. Sci. USA 105, 5986–5991; 2008; PLoS ONE 3, e3942; 2008). However, they had not determined precisely how the antibodies bound the virus, making it difficult to design vaccines that elicited the responses of these antibodies.

In February, two independent research teams described how a number of human antibodies latch onto and neutralize multiple influenza A strains, including the 1918 pandemic H1 virus and the H5 bird flu virus. The research teams showed that these antibodies bind the same genetically stable region on the 'neck' of the influenza hemagglutinin protein, thereby preventing the virus from fusing with human host cells. Scientists say that antibodies that target conserved regions of the virus could be combined with antiviral medicine to treat flu victims.

To identify such antibodies, the two groups used white blood cells from healthy immunized volunteers. “Both groups screened different libraries of human antibodies in search of those with neutralizing activity against a broad range of influenza virus subtypes,” says Rachelle Salomon of the US National Institute of Allergy and Infectious Diseases (NIAID).

Although the two groups identified different antibodies, the antibodies bound the same general region of the flu virus. A team led by Wayne Marasco of the Dana-Farber Cancer Institute and Harvard Medical School in Boston identified multiple human antibodies that bound a genetically stable pocket in the neck of the hemagglutinin protein (Nat. Struct. Mol. Biol., doi:10.1038/nsmb.1566; 2009). Similarly, Ian Wilson of the Scripps Research Institute in La Jolla, California and his colleagues reported that the CR6261 antibody bound the same region of the hemagglutinin protein as did the antibodies identified by Marasco's team (Science, doi:10.1126/science.1171491; 2009). Part of Wilson's team had previously identified CR6261 (PLoS ONE 3, e3942; 2008). When tested in mice, CR6261 and three of the antibodies identified by Marasco's team protected the mice from multiple influenza A strains.

Although it is possible this research could lead to the development of more effective antibody-based drugs and influenza vaccines, NIAID director Anthony Fauci cautions that there is much more work to be done. This research “ultimately could have a big impact, but it has to go through the step-by-step processes,” Fauci says. He explains that “at any step in the process, it may run into some substantial blocks.”