Molecular characterization of the monoclonal antibodies composing ZMAb: A protective cocktail against ebola virus

Jonathan Audet, Gary Wong, Han Wang, Guangwen Lu, George F. Gao, Gary Kobinger, Xiangguo Qiu

Research output: Contribution to journalArticlepeer-review

81 Scopus citations

Abstract

Ebola virus (EBOV) causes severe viral hemorrhagic fever in humans and non-human primates, with a case fatality rate of up to 88% in human outbreaks. Over the past 3 years, monoclonal antibody (mAb) cocktails have demonstrated high efficacy as treatments against EBOV infection. One such cocktail is ZMAb, which consists of three mouse antibodies, 1H3, 2G4, and 4G7. Here, we present the epitope binding properties of mAbs 1H3, 2G4, and 4G7. We showed that these antibodies have different variable region sequences, suggesting that the individual mAbs are not clonally related. All three antibodies were found to neutralize EBOV variant Mayinga. Additionally, 2G4 and 4G7 were shown to cross-inhibit each other in vitro and select for an escape mutation at the same position on the EBOV glycoprotein (GP), at amino acid 508. 1H3 selects an escape mutant at amino acid 273 on EBOV GP. Surface plasmon resonance studies showed that all three antibodies have dissociation constants on the order of 107. In combination with previous studies evaluating the binding sites of other protective antibodies, our results suggest that antibodies targeting the GP1-GP2 interface and the glycan cap are often selected as efficacious antibodies for post-exposure interventions against EBOV.

Original languageEnglish (US)
Article number6881
JournalScientific reports
Volume4
DOIs
StatePublished - 2014
Externally publishedYes

ASJC Scopus subject areas

  • General

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