Single-cell analysis of memory B cells from top neutralizers reveals multiple sites of vulnerability within HCMV Trimer and Pentamer.

HCMV Pentamer Trimer antiviral therapy broadly neutralizing antibody cryogenic electron microscopy epitope map neutralizaton mechanisms single B cell

Journal

Immunity
ISSN: 1097-4180
Titre abrégé: Immunity
Pays: United States
ID NLM: 9432918

Informations de publication

Date de publication:
14 Nov 2023
Historique:
received: 23 03 2023
revised: 02 07 2023
accepted: 18 10 2023
medline: 4 12 2023
pubmed: 16 11 2023
entrez: 15 11 2023
Statut: ppublish

Résumé

Human cytomegalovirus (HCMV) can cause severe diseases in fetuses, newborns, and immunocompromised individuals. Currently, no vaccines are approved, and treatment options are limited. Here, we analyzed the human B cell response of four HCMV top neutralizers from a cohort of 9,000 individuals. By single-cell analyses of memory B cells targeting the pentameric and trimeric HCMV surface complexes, we identified vulnerable sites on the shared gH/gL subunits as well as complex-specific subunits UL

Identifiants

pubmed: 37967532
pii: S1074-7613(23)00449-1
doi: 10.1016/j.immuni.2023.10.009
pii:
doi:

Substances chimiques

Viral Envelope Proteins 0
Membrane Glycoproteins 0
Antibodies, Neutralizing 0
Antibodies, Viral 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

2602-2620.e10

Subventions

Organisme : NIAID NIH HHS
ID : R01 AI097274
Pays : United States

Informations de copyright

Copyright © 2023 Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests A patent application encompassing aspects of this work has been filed by the University of Cologne, the University of Ulm, and the University of Duisburg-Essen, listing F.K., C. Sinzger, A.K., M.Z., and M.A. as inventors.

Auteurs

Matthias Zehner (M)

Laboratory of Experimental Immunology, Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany. Electronic address: matthias.zehner@uk-koeln.de.

Mira Alt (M)

Department of Infectious Diseases, West German Centre of Infectious Diseases, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany.

Artem Ashurov (A)

Laboratory of Experimental Immunology, Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany.

Jory A Goldsmith (JA)

Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.

Rebecca Spies (R)

Institute for Virology, Ulm University Medical Center, 89081 Ulm, Germany.

Nina Weiler (N)

Institute for Virology, Ulm University Medical Center, 89081 Ulm, Germany.

Justin Lerma (J)

Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.

Lutz Gieselmann (L)

Laboratory of Experimental Immunology, Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany; German Center for Infection Research, Partner Site Bonn-Cologne, 50931 Cologne, Germany.

Dagmar Stöhr (D)

Institute for Virology, Ulm University Medical Center, 89081 Ulm, Germany.

Henning Gruell (H)

Laboratory of Experimental Immunology, Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany.

Eric P Schultz (EP)

Division of Biological Sciences, University of Montana, Missoula, MT 59812, USA; Center for Biomolecular Structure and Dynamics, University of Montana, Missoula, MT 59812, USA.

Christoph Kreer (C)

Laboratory of Experimental Immunology, Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany.

Linda Schlachter (L)

Laboratory of Experimental Immunology, Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany.

Hanna Janicki (H)

Laboratory of Experimental Immunology, Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany.

Kerstin Laib Sampaio (K)

Institute for Virology, Ulm University Medical Center, 89081 Ulm, Germany.

Cora Stegmann (C)

Division of Biological Sciences, University of Montana, Missoula, MT 59812, USA; Center for Biomolecular Structure and Dynamics, University of Montana, Missoula, MT 59812, USA.

Michelle D Nemetchek (MD)

Division of Biological Sciences, University of Montana, Missoula, MT 59812, USA; Center for Biomolecular Structure and Dynamics, University of Montana, Missoula, MT 59812, USA.

Sabrina Dähling (S)

Laboratory of Experimental Immunology, Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany.

Leon Ullrich (L)

Laboratory of Experimental Immunology, Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany.

Ulf Dittmer (U)

Institute for Virology, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany.

Oliver Witzke (O)

Department of Infectious Diseases, West German Centre of Infectious Diseases, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany.

Manuel Koch (M)

Institute for Dental Research and Oral Musculoskeletal Biology, Center for Biochemistry, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany.

Brent J Ryckman (BJ)

Division of Biological Sciences, University of Montana, Missoula, MT 59812, USA; Center for Biomolecular Structure and Dynamics, University of Montana, Missoula, MT 59812, USA.

Ramin Lotfi (R)

Institute for Transfusion Medicine, Ulm University Medical Center, 89081 Ulm, Germany.

Jason S McLellan (JS)

Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.

Adalbert Krawczyk (A)

Department of Infectious Diseases, West German Centre of Infectious Diseases, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany; Institute for Virology, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany.

Christian Sinzger (C)

Institute for Virology, Ulm University Medical Center, 89081 Ulm, Germany.

Florian Klein (F)

Laboratory of Experimental Immunology, Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany; German Center for Infection Research, Partner Site Bonn-Cologne, 50931 Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), University Hospital of Cologne, 50931 Cologne, Germany. Electronic address: florian.klein@uk-koeln.de.

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