Mechanistic and Fc Requirements for Inhibition of Sudan Virus Entry and In Vivo Protection by a Synthetic Antibody.

Authors: Hofmann D, Zak SE, Nyakatura EK, Mittler E, Bakken RR, Chandran K, Dye JM, Lai JR Abstract The Sudan virus (SUDV), an ebolavirus species, causes severe hemorrhagic fever with human case fatality rates of ∼50%. Previous work from our lab demonstrated the synthetic antibody F4 potently inhibits viral entry and protects against lethal virus challenge in mice [Chen et al., ACS Chem. Biol., 2014, 9, 2263-2273]. Here, we explore mechanistic requirements as well as contribution of the Fc region and function on neutralization and in vivo protection. Live cell imaging demonstrates that the antibody colocalizes with vesicular stomatitis virus particles containing the Sudan virus glycoprotein (VSV-GPSUDV) and that the antibody is rapidly degraded within cellular endosomes. Viral es...

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