6UYE

EBOV GPdMuc Makona bound to rEBOV-548 Fab

Summary for 6UYE

• Entry DOI: 10.2210/pdb6uye/pdb
• EMDB information: 20947
• Descriptor: SGP, Virion spike glycoprotein, Antibody rEBOV-548 Fab, heavy chain, ... (8 entities in total)
• Functional Keywords: antibody, ebola, synergy, cross-reactive, therapeutic, viral protein-immune system complex, viral protein/immune system
• Biological source: Ebola virus; More
• Total number of polymer chains: 12
• Total formula weight: 206398.84

Authors

Murin, C.D.,Ward, A.B. (deposition date: 2019-11-13, release date: 2020-03-11, Last modification date: 2024-10-23)

Primary citation

Gilchuk, P.,Murin, C.D.,Milligan, J.C.,Cross, R.W.,Mire, C.E.,Ilinykh, P.A.,Huang, K.,Kuzmina, N.,Altman, P.X.,Hui, S.,Gunn, B.M.,Bryan, A.L.,Davidson, E.,Doranz, B.J.,Turner, H.L.,Alkutkar, T.,Flinko, R.,Orlandi, C.,Carnahan, R.,Nargi, R.,Bombardi, R.G.,Vodzak, M.E.,Li, S.,Okoli, A.,Ibeawuchi, M.,Ohiaeri, B.,Lewis, G.K.,Alter, G.,Bukreyev, A.,Saphire, E.O.,Geisbert, T.W.,Ward, A.B.,Crowe Jr., J.E.
Analysis of a Therapeutic Antibody Cocktail Reveals Determinants for Cooperative and Broad Ebolavirus Neutralization.
Immunity, 52:388-403.e12, 2020

PubMed Abstract: Structural principles underlying the composition of protective antiviral monoclonal antibody (mAb) cocktails are poorly defined. Here, we exploited antibody cooperativity to develop a therapeutic mAb cocktail against Ebola virus. We systematically analyzed the antibody repertoire in human survivors and identified a pair of potently neutralizing mAbs that cooperatively bound to the ebolavirus glycoprotein (GP). High-resolution structures revealed that in a two-antibody cocktail, molecular mimicry was a major feature of mAb-GP interactions. Broadly neutralizing mAb rEBOV-520 targeted a conserved epitope on the GP base region. mAb rEBOV-548 bound to a glycan cap epitope, possessed neutralizing and Fc-mediated effector function activities, and potentiated neutralization by rEBOV-520. Remodeling of the glycan cap structures by the cocktail enabled enhanced GP binding and virus neutralization. The cocktail demonstrated resistance to virus escape and protected non-human primates (NHPs) against Ebola virus disease. These data illuminate structural principles of antibody cooperativity with implications for development of antiviral immunotherapeutics.

PubMed: 32023489
DOI: 10.1016/j.immuni.2020.01.001

Experimental method

ELECTRON MICROSCOPY (3.96 Å)