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The evolution and determinants of neutralization of potent head-binding antibodies against Ebola virus.
Yu, Xiaoying; Hastie, Kathryn M; Davis, Carl W; Avalos, Ruben Diaz; Williams, Dewight; Parekh, Diptiben; Hui, Sean; Mann, Colin; Hariharan, Chitra; Takada, Ayato; Ahmed, Rafi; Saphire, Erica Ollmann.
Affiliation
  • Yu X; Center for Infectious Disease and Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, CA 92037, USA.
  • Hastie KM; Center for Infectious Disease and Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, CA 92037, USA.
  • Davis CW; Emory Vaccine Center and Department of Microbiology and Immunology, Emory University, Atlanta, GA 30322, USA.
  • Avalos RD; Center for Infectious Disease and Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, CA 92037, USA.
  • Williams D; Eyring Materials Center, Arizona State University, Tempe, AZ 85281, USA.
  • Parekh D; Center for Infectious Disease and Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, CA 92037, USA.
  • Hui S; Center for Infectious Disease and Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, CA 92037, USA.
  • Mann C; Center for Infectious Disease and Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, CA 92037, USA.
  • Hariharan C; Center for Infectious Disease and Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, CA 92037, USA.
  • Takada A; Division of Global Epidemiology, International Institute for Zoonosis Control, Hokkaido University, Sapporo 001-0020, Japan.
  • Ahmed R; Emory Vaccine Center and Department of Microbiology and Immunology, Emory University, Atlanta, GA 30322, USA.
  • Saphire EO; 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. Electronic address: erica@lji.org.
Cell Rep ; 42(11): 113366, 2023 11 28.
Article in En | MEDLINE | ID: mdl-37938974
ABSTRACT
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Hemorrhagic Fever, Ebola / Ebolavirus Limits: Humans Language: En Journal: Cell Rep Year: 2023 Document type: Article Affiliation country: United States

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Hemorrhagic Fever, Ebola / Ebolavirus Limits: Humans Language: En Journal: Cell Rep Year: 2023 Document type: Article Affiliation country: United States