Polyclonal and convergent antibody response to Ebola virus vaccine rVSV-ZEBOV
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Polyclonal and convergent antibody response to Ebola virus vaccine rVSV-ZEBOV. / Ehrhardt, Stefanie A; Zehner, Matthias; Krähling, Verena; Cohen-Dvashi, Hadas; Kreer, Christoph; Elad, Nadav; Gruell, Henning; Ercanoglu, Meryem S; Schommers, Philipp; Gieselmann, Lutz; Eggeling, Ralf; Dahlke, Christine; Wolf, Timo; Pfeifer, Nico; Addo, Marylyn M; Diskin, Ron; Becker, Stephan; Klein, Florian.
in: NAT MED, Jahrgang 25, Nr. 10, 10.2019, S. 1589-1600.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Polyclonal and convergent antibody response to Ebola virus vaccine rVSV-ZEBOV
AU - Ehrhardt, Stefanie A
AU - Zehner, Matthias
AU - Krähling, Verena
AU - Cohen-Dvashi, Hadas
AU - Kreer, Christoph
AU - Elad, Nadav
AU - Gruell, Henning
AU - Ercanoglu, Meryem S
AU - Schommers, Philipp
AU - Gieselmann, Lutz
AU - Eggeling, Ralf
AU - Dahlke, Christine
AU - Wolf, Timo
AU - Pfeifer, Nico
AU - Addo, Marylyn M
AU - Diskin, Ron
AU - Becker, Stephan
AU - Klein, Florian
PY - 2019/10
Y1 - 2019/10
N2 - 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.
AB - 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.
KW - Adult
KW - Antibodies, Neutralizing/immunology
KW - Antibodies, Viral/immunology
KW - Antibody Formation/immunology
KW - B-Lymphocytes/immunology
KW - Ebola Vaccines/administration & dosage
KW - Ebolavirus/immunology
KW - Female
KW - Hemorrhagic Fever, Ebola/immunology
KW - Humans
KW - Immunity, Humoral/immunology
KW - Male
KW - Middle Aged
KW - Vaccination/adverse effects
KW - Vesiculovirus/genetics
KW - Volunteers
U2 - 10.1038/s41591-019-0602-4
DO - 10.1038/s41591-019-0602-4
M3 - SCORING: Journal article
C2 - 31591605
VL - 25
SP - 1589
EP - 1600
JO - NAT MED
JF - NAT MED
SN - 1078-8956
IS - 10
ER -