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TitlePolyclonal and convergent antibody response to Ebola virus vaccine rVSV-ZEBOV.
Journal, issue, pagesNat Med, Vol. 25, Issue 10, Page 1589-1600, Year 2019
Publish dateOct 7, 2019
AuthorsStefanie A Ehrhardt / Matthias Zehner / Verena Krähling / Hadas Cohen-Dvashi / Christoph Kreer / Nadav Elad / Henning Gruell / Meryem S Ercanoglu / Philipp Schommers / Lutz Gieselmann / Ralf Eggeling / Christine Dahlke / Timo Wolf / Nico Pfeifer / Marylyn M Addo / Ron Diskin / Stephan Becker / Florian Klein /
PubMed AbstractRecombinant 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) ...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.
External linksNat Med / PubMed:31591605
MethodsEM (single particle)
Resolution3.1 - 3.3 Å
Structure data

4520

6qd7

EMDB-4520, PDB-6qd7:
EM structure of a EBOV-GP bound to 3T0331 neutralizing antibody
Method: EM (single particle) / Resolution: 3.1 Å

4521

6qd8

EMDB-4521, PDB-6qd8:
EM structure of a EBOV-GP bound to 4M0368 neutralizing antibody
Method: EM (single particle) / Resolution: 3.3 Å

Chemicals

ChemComp-MAN:
alpha-D-mannopyranose / Mannose

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

Source
  • ebola virus
  • homo sapiens (human)
KeywordsVIRAL PROTEIN / Antibody / immune response / viral infection / EBOV

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