Identification and Structure of a Multidonor Class of Head-Directed Influenza-Neutralizing Antibodies Reveal the Mechanism for Its Recurrent Elicitation.

Antibodies, Neutralizing / immunology Humans Influenza, Human / virology Molecular Structure
Influenza X-ray crystal structure elicitation frequency germline-reverted hemagglutinin multidonor antibody class neutralizing antibodies recurrent elication sialic acid-binding site vaccination

Journal

Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691

Informations de publication

Date de publication:
01 09 2020
Historique:
received: 03 12 2019
revised: 12 05 2020
accepted: 07 08 2020
entrez: 3 9 2020
pubmed: 3 9 2020
medline: 29 5 2021
Statut: ppublish

Résumé

Multidonor antibodies are of interest for vaccine design because they can in principle be elicited in the general population by a common set of immunogens. For influenza, multidonor antibodies have been observed against the hemagglutinin (HA) stem, but not the immunodominant HA head. Here, we identify and characterize a multidonor antibody class (LPAF-a class) targeting the HA head. This class exhibits potent viral entry inhibition against H1N1 A/California/04/2009 (CA09) virus. LPAF-a class antibodies derive from the HV2-70 gene and contain a "Tyr-Gly-Asp"-motif, which occludes the HA-sialic acid binding site as revealed by a co-crystal structure with HA. Both germline-reverted and mature LPAF antibodies potently neutralize CA09 virus and have nanomolar affinities for CA09 HA. Moreover, increased frequencies for LPFA-a class antibodies are observed in humans after a single vaccination. Overall, this work highlights the identification of a multidonor class of head-directed influenza-neutralizing antibodies and delineates the mechanism of their recurrent elicitation in humans.

Identifiants

DOI: 10.1016/j.celrep.2020.108088 PMID: 32877670
pubmed: 32877670
pii: S2211-1247(20)31077-9
doi: 10.1016/j.celrep.2020.108088
pii:
doi:

Substances chimiques

Antibodies, Neutralizing 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

108088

Informations de copyright

Published by Elsevier Inc.

Déclaration de conflit d'intérêts

Declaration of Interests The authors declare no competing interests.

Auteurs

Crystal Sao-Fong Cheung (CS)

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

Alexander Fruehwirth (A)

Institute for Research in Biomedicine, Università della Svizzera italiana, 6500 Bellinzona, Switzerland.

Philipp Carl Georg Paparoditis (PCG)

Institute for Research in Biomedicine, Università della Svizzera italiana, 6500 Bellinzona, Switzerland.

Chen-Hsiang Shen (CH)

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

Mathilde Foglierini (M)

Institute for Research in Biomedicine, Università della Svizzera italiana, 6500 Bellinzona, Switzerland.

M Gordon Joyce (MG)

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

Kwanyee Leung (K)

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

Luca Piccoli (L)

Institute for Research in Biomedicine, Università della Svizzera italiana, 6500 Bellinzona, Switzerland.

Reda Rawi (R)

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

Chiara Silacci-Fregni (C)

Institute for Research in Biomedicine, Università della Svizzera italiana, 6500 Bellinzona, Switzerland.

Yaroslav Tsybovsky (Y)

Electron Microscopy Laboratory, Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.

Raffaello Verardi (R)

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

Lingshu Wang (L)

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

Shuishu Wang (S)

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

Eun Sung Yang (ES)

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

Baoshan Zhang (B)

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

Yi Zhang (Y)

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

Gwo-Yu Chuang (GY)

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

Davide Corti (D)

Institute for Research in Biomedicine, Università della Svizzera italiana, 6500 Bellinzona, Switzerland.

John R Mascola (JR)

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

Lawrence Shapiro (L)

Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA.

Peter D Kwong (PD)

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA. Electronic address: pdkwong@nih.gov.

Antonio Lanzavecchia (A)

Institute for Research in Biomedicine, Università della Svizzera italiana, 6500 Bellinzona, Switzerland. Electronic address: lanzavecchia@irb.usi.ch.

Tongqing Zhou (T)

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: tzhou@nih.gov.

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Classifications MeSH

questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Anticorps neutralisants › Identification and Structure of a Multidonor...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Identification and Structure of a Multidonor...
questionsmedicales.fr › Maladies de l'appareil respiratoire › Infections de l'appareil respiratoire › Grippe humaine › Identification and Structure of a Multidonor...
questionsmedicales.fr › Phénomènes chimiques › Structure moléculaire › Identification and Structure of a Multidonor...