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Cell Host Microbe. 2020 Mar 11;27(3):418-427.e4. doi: 10.1016/j.chom.2020.01.007. Epub 2020 Feb 13.

Structural Basis for a Convergent Immune Response against Ebola Virus.

Author information

1
Department of Structural Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
2
Laboratory of Experimental Immunology, Institute of Virology, Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne 50931, Germany.
3
Department of Chemical Research Support, Weizmann Institute of Science, Rehovot 76100, Israel.
4
Laboratory of Experimental Immunology, Institute of Virology, Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne 50931, Germany; German Center for Infection Research, Partner Site Bonn-Cologne, Cologne 50931, Germany; Center for Molecular Medicine Cologne (CMMC), University Hospital of Cologne, Cologne, Germany.
5
Department of Structural Biology, Weizmann Institute of Science, Rehovot 76100, Israel. Electronic address: ron.diskin@weizmann.ac.il.

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 VH3-15/Vλ1-40-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 VH3-15/Vλ1-40 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 VH3-15/Vλ1-40 germline genes for specifically targeting this site and highlights Ebolavirus species-specific sequence divergences that may restrict breadth of VH3-15/Vλ1-40-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.

KEYWORDS:

Ebola virus; antibodies; electron microscopy; immune response; protein structure

PMID:
32059794
DOI:
10.1016/j.chom.2020.01.007
[Indexed for MEDLINE]

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