The evolution and determinants of neutralization of potent head-binding antibodies against Ebola virus

Xiaoying Yu; Kathryn M. Hastie; Carl W. Davis; Ruben Diaz Avalos; Dewight Williams; Diptiben Parekh; Sean Hui; Colin Mann; Chitra Hariharan; Ayato Takada; Rafi Ahmed; Erica Ollmann Saphire

Cell Reports (Nov 2023)

The evolution and determinants of neutralization of potent head-binding antibodies against Ebola virus

Xiaoying Yu,
Kathryn M. Hastie,
Carl W. Davis,
Ruben Diaz Avalos,
Dewight Williams,
Diptiben Parekh,
Sean Hui,
Colin Mann,
Chitra Hariharan,
Ayato Takada,
Rafi Ahmed,
Erica Ollmann Saphire

Affiliations

Xiaoying Yu: Center for Infectious Disease and Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, CA 92037, USA
Kathryn M. Hastie: Center for Infectious Disease and Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, CA 92037, USA
Carl W. Davis: Emory Vaccine Center and Department of Microbiology and Immunology, Emory University, Atlanta, GA 30322, USA
Ruben Diaz Avalos: Center for Infectious Disease and Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, CA 92037, USA
Dewight Williams: Eyring Materials Center, Arizona State University, Tempe, AZ 85281, USA
Diptiben Parekh: Center for Infectious Disease and Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, CA 92037, USA
Sean Hui: Center for Infectious Disease and Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, CA 92037, USA
Colin Mann: Center for Infectious Disease and Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, CA 92037, USA
Chitra Hariharan: Center for Infectious Disease and Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, CA 92037, USA
Ayato Takada: Division of Global Epidemiology, International Institute for Zoonosis Control, Hokkaido University, Sapporo 001-0020, Japan
Rafi Ahmed: Emory Vaccine Center and Department of Microbiology and Immunology, Emory University, Atlanta, GA 30322, USA
Erica Ollmann Saphire: Center for Infectious Disease and Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, CA 92037, USA; Department of Medicine, University of California, San Diego, San Diego, CA 92093, USA; Corresponding author

Journal volume & issue: Vol. 42, no. 11
p. 113366

Abstract

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Summary: Monoclonal antibodies against the Ebola virus (EBOV) surface glycoprotein are effective treatments for EBOV disease. Antibodies targeting the EBOV glycoprotein (GP) head epitope have potent neutralization and Fc effector function activity and thus are of high interest as therapeutics and for vaccine design. Here we focus on the head-binding antibodies 1A2 and 1D5, which have been identified previously in a longitudinal study of survivors of EBOV infection. 1A2 and 1D5 have the same heavy- and light-chain germlines despite being isolated from different individuals and at different time points after recovery from infection. Cryoelectron microscopy analysis of each antibody in complex with the EBOV surface GP reveals key amino acid substitutions in 1A2 that contribute to greater affinity, improved neutralization potency, and enhanced breadth as well as two strategies for antibody evolution from a common site.

CP: Immunology

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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