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Engineered Fc g-receptor engagement enhances broadly neutralizing antibodies (bNAbs) against influenza A virus

Mouse studies suggest bNAbs engineered to activate Fc g-receptors on immune cells could help prevent influenza infection. bNAbs that bind the invariant stalk region of hemagglutinin (HA) were modified with Fc regions designed to bind a subset of Fc g-receptors on immune cells that activate an antiviral response. In a mouse model of lethal influenza infection, the engineered bNAbs increased survival and decreased viral titers in the lung compared with antibodies containing Fc regions that engaged inhibitory Fc g-receptors or were deficient in Fc g-receptor binding. In humanized mice exclusively expressing human Fc g-receptors, an engineered HA stalk-specific bNAb increased survival after viral infection compared with an unmodified bNAb. Next steps could include building Fc portions into therapeutic bNAbs that enable interactions with activating Fc g-receptors in the host.

SciBX 7(6); doi:10.1038/scibx.2014.185
Published online Feb. 13, 2014

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DiLillo, D.J. et al. Nat. Med.;
published online Jan. 12, 2014;
Contact: Jeffrey V. Ravetch,
The Rockefeller University, New York, N.Y.