Universität zu Köln

Ehrhardt, Stefanie A., Zehner, Matthias, Kraehling, Verena, Cohen-Dvashi, Hadas, Kreer, Christoph ORCID: 0000-0002-9140-9850, Elad, Nadav ORCID: 0000-0001-6222-2280, Gruell, Henning, Ercanoglu, Meryem S., Schommers, Philipp ORCID: 0000-0003-3375-6800, Gieselmann, Lutz, Eggeling, Ralf ORCID: 0000-0002-3583-1029, Dahlke, Christine, Wolf, Timo, Pfeifer, Nico, Addo, Marylyn M., Diskin, Ron, Becker, Stephan and Klein, Florian (2019). Polyclonal and convergent antibody response to Ebola virus vaccine rVSV-ZEBOV. Nat. Med., 25 (10). S. 1589 - 1614. NEW YORK: NATURE PUBLISHING GROUP. ISSN 1546-170X

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Ehrhardt, Stefanie A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Zehner, Matthias UNSPECIFIED UNSPECIFIED UNSPECIFIED Kraehling, Verena UNSPECIFIED UNSPECIFIED UNSPECIFIED Cohen-Dvashi, Hadas UNSPECIFIED UNSPECIFIED UNSPECIFIED Kreer, Christoph UNSPECIFIED orcid.org/0000-0002-9140-9850 UNSPECIFIED Elad, Nadav UNSPECIFIED orcid.org/0000-0001-6222-2280 UNSPECIFIED Gruell, Henning UNSPECIFIED UNSPECIFIED UNSPECIFIED Ercanoglu, Meryem S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schommers, Philipp UNSPECIFIED orcid.org/0000-0003-3375-6800 UNSPECIFIED Gieselmann, Lutz UNSPECIFIED UNSPECIFIED UNSPECIFIED Eggeling, Ralf UNSPECIFIED orcid.org/0000-0002-3583-1029 UNSPECIFIED Dahlke, Christine UNSPECIFIED UNSPECIFIED UNSPECIFIED Wolf, Timo UNSPECIFIED UNSPECIFIED UNSPECIFIED Pfeifer, Nico UNSPECIFIED UNSPECIFIED UNSPECIFIED Addo, Marylyn M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Diskin, Ron UNSPECIFIED UNSPECIFIED UNSPECIFIED Becker, Stephan UNSPECIFIED UNSPECIFIED UNSPECIFIED Klein, Florian UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-132778
DOI:	10.1038/s41591-019-0602-4
Journal or Publication Title:	Nat. Med.
Volume:	25
Number:	10
Page Range:	S. 1589 - 1614
Date:	2019
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	NEW YORK
ISSN:	1546-170X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language HUMAN MONOCLONAL-ANTIBODIES; NEUTRALIZING ANTIBODIES; MEDIATED PROTECTION; GLYCOPROTEIN; INFECTION; COCKTAIL; FEATURES; DISEASE; SYSTEM; TRIAL Multiple languages Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/13277