Cooperativity Enables Non-neutralizing Antibodies to Neutralize Ebolavirus.

ABSTRACT: Drug combinations are synergistic when their combined efficacy exceeds the sum of the individual actions, but they rarely include ineffective drugs that become effective only in combination. We identified several "enabling pairs" of neutralizing and non-neutralizing anti-ebolavirus monoclonal antibodies, whose combination exhibited new functional profiles, including transforming a non-neutralizing antibody to a neutralizer. Sub-neutralizing concentrations of antibodies 2G4 or m8C4 enabled non-neutralizing antibody FVM09 (IC₅₀ >1 μM) to exhibit potent neutralization (IC₅₀ 1-10 nM). While FVM09 or m8C4 alone failed to protect Ebola-virus-infected mice, a combination of the two antibodies provided 100% protection. Furthermore, non-neutralizers FVM09 and FVM02 exponential

SUBMITTER: Howell KA 

PROVIDER: S-EPMC6082427 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature