@article{8bc4a009ff76429ab47df9a21a7cf034,
title = "Structural Basis for a Convergent Immune Response against Ebola Virus",
abstract = "Ebola virus disease is a severe health problem in Africa. Vaccines that display the Zaire ebolavirus glycoprotein spike complex are a prime component for the effort to combat it. The V(H)3-15/V(lambda)1-40-based class of antibodies was recently discovered to be a common response in individuals who received the Ebola virus vaccines. These antibodies display attractive properties, and thus likely contribute to the efficacy of the vaccines. Here, we use cryo-EM to elucidate how three V(H)3-15/V(lambda)1-40 antibodies from different individuals target the virus and found a convergent mechanism against a partially conserved site on the spike complex. Our study rationalizes the selection of the V(H)3-15/V(lambda)1-40 germline genes for specifically targeting this site and highlights Ebolavirus species-specific sequence divergences that may restrict breadth of V(H)3-15/V(lambda)1-40-based humoral response. The results from this study could help develop improved immunization schemes and further enable the design of immunogens that would be efficacious against a broader set of Ebolavirus species.",
author = "Hadas Cohen-Dvashi and Matthias Zehner and Stefanie Ehrhardt and Nadav Elad and Florian Klein and Ron Diskin",
note = "We thank all the members of the Diskin and Klein labs for their comments and discussions. Electron microscopy studies were supported in part by the Irving and Cherna Moskowitz Center for Nano and Bio-Nano Imaging at the Weizmann Institute of Science. The lab of R.D. is funded by the I-CORE Program of the Planning and Budgeting Committee and the Israel Science Foundation (grant nos. 1775/12 and 682/16), the Moross Integrated Cancer Center, the Dr. Barry Sherman Institute for Medicinal Chemistry, the Jeanne and Joseph Nissim Center for Life Sciences Research, and the Estate of Emile Mimran. Support was further provided by the German Center for Infection Research (DZIF to F.K.), the German Research Foundation (CRC1310 to F.K.), and the European Research Council (ERC-StG639961 to F.K.). Coordinate files and density maps were deposited and are available at the protein data bank under accession codes: 6S8D, 6S8I, and 6S8J for EBOV GP/1T0277, EBOV GP/3T0265, and EBOV GP/5T0180, respectively. Author Contributions R.D. and F.K. designed and oversaw the project. H.C.-D. and M.K. produced proteins. H.C.-D. performed binding studies. H.C.-D. and N.E. collected EM data. R.D. and H.C.-D. solved structures and performed structural analysis. M.Z. and S.E. cloned and produced antibodies. M.Z. produced proteins and performed binding experiments as well as generated sequence alignments. R.D. wrote the manuscript with the help of all other authors.",
year = "2020",
month = mar,
day = "11",
doi = "https://doi.org/10.1016/j.chom.2020.01.007",
language = "الإنجليزيّة",
volume = "27",
pages = "418--427.e4",
journal = "Cell Host & Microbe",
issn = "1931-3128",
publisher = "Cell Press",
number = "3",
}