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Biological Chemistry

Antibody One-Two Could Knock Out Flu

by Carmen Drahl
July 11, 2011 | A version of this story appeared in Volume 89, Issue 28

A cocktail of two antibodies might be enough to combat most varieties of influenza A, the virus behind seasonal flu and flu pandemics, a study suggests (Science, DOI: 10.1126/science.1204839). The combination approach could lead to a universal flu vaccine, a long-standing goal in an area where new vaccines must be developed each year by predicting which types of flu will dominate the coming season. Jaap Goudsmit of Dutch biopharmaceutical company CrucellIan A. Wilson and Damian C. Ekiert of Scripps Research Institute, and colleagues previously uncovered an antibody that neutralizes multiple types of influenza A. The antibody binds hemagglutinin, the virus’s major envelope glycoprotein (C&EN, March 2, 2009, page 11). The antibody works best against influenza A’s group 1 subtype, likely because protein sequence and glycan differences in group 2 viruses restrict the antibody’s binding. Crucell has now found an antibody called CR8020 that neutralizes the group 2 flu viruses in mice. Wilson’s team showed that, like the previous antibody, CR8020 binds to hemagglutinin’s stalk, but at a different site farther down the stalk. Crucell has filed a patent application for CR8020.

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Credit: Courtesy of Daiman Ekiert and Ian Wilson
This X-ray structure depicts CR8020 (red) binding to the stem of hemagglutinin (green) from the 1968 Hong Kong flu virus; glycans are depicted as purple space-filling models.
X-ray crystal structure of a trimer of Hong Kong flu hemagglutinin (green) binding to an antibondy (red) that defuses its activity. Glycans are in blue
Credit: Courtesy of Daiman Ekiert and Ian Wilson
This X-ray structure depicts CR8020 (red) binding to the stem of hemagglutinin (green) from the 1968 Hong Kong flu virus; glycans are depicted as purple space-filling models.

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