Synthetic Antibodies with a Human Framework That Protect
Mice from Lethal Sudan Ebolavirus Challenge
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Abstract
The ebolaviruses cause severe and
rapidly progressing hemorrhagic
fever. There are five ebolavirus species; although much is known about
Zaire ebolavirus (EBOV) and its neutralization by antibodies, little
is known about Sudan ebolavirus (SUDV), which is emerging with increasing
frequency. Here we describe monoclonal antibodies containing a human
framework that potently inhibit infection by SUDV and protect mice
from lethal challenge. The murine antibody 16F6, which binds the SUDV
envelope glycoprotein (GP), served as the starting point for design.
Sequence and structural alignment revealed similarities between 16F6
and YADS1, a synthetic antibody with a humanized scaffold. A focused
phage library was constructed and screened to impart 16F6-like recognition
properties onto the YADS1 scaffold. A panel of 17 antibodies were
characterized and found to have a range of neutralization potentials
against a pseudotype virus infection model. Neutralization correlated
with GP binding as determined by ELISA. Two of these clones, E10 and
F4, potently inhibited authentic SUDV and conferred protection and
memory immunity in mice from lethal SUDV challenge. E10 and F4 were
further shown to bind to the same epitope on GP as 16F6 with comparable
affinities. These antibodies represent strong immunotherapeutic candidates
for treatment of SUDV infection