Anti-Ebolavirus, GP (Clone EBOV-548) - Purified No Carrier Protein (E172-GRP)

Ebola virus is a member of the Filoviridae family that causes severe disease in humans with a mortality rate of 25-90%1. Three Ebola species are responsible for lethal outbreaks: Zaire ebolavirus (EBOV), Bundibugyo ebolavirus (BDBV), and Sudan ebolavirus (SUDV). The Ebola virus envelope contains a single surface glycoprotein (GP) which is responsible for viral attachment to the host cell, endosomal entry, and membrane fusion1. GP is composed of two subunits, GP1 and GP2. GP1 has a heavily glycosylated mucin-like domain and a glycan cap. GP2 contains the internal fusion loop, transmembrane domain, and stalk. GP is the major target of neutralizing monoclonal antibody (mAb) and vaccine design against Ebola virus1,2,3,4. EBOV-548 is a pan-EBOV-neutralizing mAb isolated from a survivor of the EBOV 2013-2016 outbreak2. Hybridomas were generated from human peripheral blood mononuclear cells. EBOV GP-reactive memory B cells were labeled with recombinant EBOV GP protein, purified by FACS, bulk expanded on NIH 3T3 cells, bulk fused with MFP-2 myeloma cells, and screened for neutralizing activity against live and/or recombinant EBOV, BDBV, and SUDV GP. EBOV-548 reacts to all three species GPs and neutralizes EBOV and BDBV. EBOV-548 recognizes intact but not cleaved GP. EBOV-548 was identified in a study designed to develop a cooperative two-antibody cocktail with EBOV-5202,4. When paired, EBOV-548 and EBOV-520 have synergistic activity for GP binding and virus neutralization2. This is achieved mechanically. EBOV-548 binds to the glycan cap in a manner that destabilizes the GP trimer, displacing the β17-β18 loop. As a result, the glycan cap is pulled back, facilitating EBOV-520 binding and enhancing neutralization. The cooperative effect is dependent on EBOV-548 concentration. When administered together in vivo, EBOV-548 potentiates protection by EBOV-520 against SUDV, with 50% of mice surviving treatment, while only 10% survive with EBOV-520 alone.