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Nat Med. 2019 Oct 7. doi: 10.1038/s41591-019-0602-4. [Epub ahead of print]

Polyclonal and convergent antibody response to Ebola virus vaccine rVSV-ZEBOV.

Author information

1
Laboratory of Experimental Immunology, Institute of Virology, Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne, Germany.
2
Institute of Virology, Faculty of Medicine, Philipps University Marburg, Marburg, Germany.
3
German Center for Infection Research, Partner Site Gießen-Marburg-Langen, Marburg, Germany.
4
Department of Structural Biology, Weizmann Institute of Science, Rehovot, Israel.
5
Department of Chemical Research Support, Weizmann Institute of Science, Rehovot, Israel.
6
German Center for Infection Research, Partner Site Bonn-Cologne, Cologne, Germany.
7
Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
8
Methods in Medical Informatics, Department of Computer Science, University of Tübingen, Tübingen, Germany.
9
Division of Infectious Diseases, First Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
10
Department of Clinical Immunology of Infectious Diseases, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
11
German Center for Infection Research, Partner Site Hamburg-Lübeck-Borstel-Riems, Hamburg, Germany.
12
Department of Infectious Diseases, University Hospital Frankfurt, Frankfurt/Main, Germany.
13
Faculty of Medicine, University of Tübingen, Tübingen, Germany.
14
German Center for Infection Research, Partner Site Tübingen, Tübingen, Germany.
15
Laboratory of Experimental Immunology, Institute of Virology, Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne, Germany. florian.klein@uk-koeln.de.
16
German Center for Infection Research, Partner Site Bonn-Cologne, Cologne, Germany. florian.klein@uk-koeln.de.
17
Center for Molecular Medicine Cologne (CMMC), University Hospital of Cologne and University of Cologne, Cologne, Germany. florian.klein@uk-koeln.de.

Abstract

Recombinant vesicular stomatitis virus-Zaire Ebola virus (rVSV-ZEBOV) is the most advanced Ebola virus vaccine candidate and is currently being used to combat the outbreak of Ebola virus disease (EVD) in the Democratic Republic of the Congo (DRC). Here we examine the humoral immune response in a subset of human volunteers enrolled in a phase 1 rVSV-ZEBOV vaccination trial by performing comprehensive single B cell and electron microscopy structure analyses. Four studied vaccinees show polyclonal, yet reproducible and convergent B cell responses with shared sequence characteristics. EBOV-targeting antibodies cross-react with other Ebolavirus species, and detailed epitope mapping revealed overlapping target epitopes with antibodies isolated from EVD survivors. Moreover, in all vaccinees, we detected highly potent EBOV-neutralizing antibodies with activities comparable or superior to the monoclonal antibodies currently used in clinical trials. These include antibodies combining the IGHV3-15/IGLV1-40 immunoglobulin gene segments that were identified in all investigated individuals. Our findings will help to evaluate and direct current and future vaccination strategies and offer opportunities for novel EVD therapies.

PMID:
31591605
DOI:
10.1038/s41591-019-0602-4

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