Cross-reactive neutralizing human survivor monoclonal antibody BDBV223 targets the ebolavirus stalk
- The Scripps Research Inst., La Jolla, CA (United States)
- Vanderbilt Univ. Medical Center, Nashville, TN (United States)
- Univ. of Texas Medical Branch, Galveston, TX (United States); Galveston National Lab., Galveston, TX (United States)
- The Scripps Research Inst., La Jolla, CA (United States); La Jolla Inst. for Immunology La Jolla, CA (United States)
Three Ebolavirus genus viruses cause lethal disease and lack targeted therapeutics: Ebola virus, Sudan virus and Bundibugyo virus. Monoclonal antibody (mAb) cocktails against the surface glycoprotein (GP) present a potential therapeutic strategy. Here we report two crystal structures of the antibody BDBV223, alone and complexed with its GP2 stalk epitope, an interesting site for therapeutic/vaccine design due to its high sequence conservation among ebolaviruses. BDBV223, identified in a human survivor of Bundibugyo virus disease, neutralizes both Bundibugyo virus and Ebola virus, but not Sudan virus. Importantly, the structure suggests that BDBV223 binding interferes with both the trimeric bundle assembly of GP and the viral membrane by stabilizing a conformation in which the monomers are separated by GP lifting or bending. Targeted mutagenesis of BDBV223 to enhance SUDV GP recognition indicates that additional determinants of antibody binding likely lie outside the visualized interactions, and perhaps involve quaternary assembly or membrane-interacting regions.
- Research Organization:
- Argonne National Laboratory (ANL), Argonne, IL (United States)
- Sponsoring Organization:
- USDOE Office of Science (SC), Basic Energy Sciences (BES). Scientific User Facilities Division; USDOE Office of Science (SC), Biological and Environmental Research (BER); NIH/NIAID; Defense Threat Reduction Agency (DTRA); National Inst. of Health; National Inst. of General Medical Sciences
- Grant/Contract Number:
- AC02-06CH11357; AC02-76SF00515; U19 AI109711; HDTRA1-13-1-0034; F30 AI136410; P41GM103393
- OSTI ID:
- 1512998
- Journal Information:
- Nature Communications, Vol. 10, Issue 1; ISSN 2041-1723
- Publisher:
- Nature Publishing GroupCopyright Statement
- Country of Publication:
- United States
- Language:
- ENGLISH
Web of Science
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