Potent Omicron-neutralizing antibodies isolated from a patient vaccinated 6 months before Omicron emergence

Summary: Therapeutic antibodies are an important tool in the arsenal against coronavirus infection. However, most antibodies developed early in the pandemic have lost most or all efficacy against newly emergent strains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), particularly tho...

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Main Authors: Kathryn M. Hastie, Xiaoying Yu, Fernanda Ana-Sosa-Batiz, Dawid S. Zyla, Stephanie S. Harkins, Chitra Hariharan, Hal Wasserman, Michelle A. Zandonatti, Robyn Miller, Erin Maule, Kenneth Kim, Kristen M. Valentine, Sujan Shresta, Erica Ollmann Saphire
Format: Article
Language:English
Published: Elsevier 2023-05-01
Series:Cell Reports
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124723004321
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author Kathryn M. Hastie
Xiaoying Yu
Fernanda Ana-Sosa-Batiz
Dawid S. Zyla
Stephanie S. Harkins
Chitra Hariharan
Hal Wasserman
Michelle A. Zandonatti
Robyn Miller
Erin Maule
Kenneth Kim
Kristen M. Valentine
Sujan Shresta
Erica Ollmann Saphire
author_facet Kathryn M. Hastie
Xiaoying Yu
Fernanda Ana-Sosa-Batiz
Dawid S. Zyla
Stephanie S. Harkins
Chitra Hariharan
Hal Wasserman
Michelle A. Zandonatti
Robyn Miller
Erin Maule
Kenneth Kim
Kristen M. Valentine
Sujan Shresta
Erica Ollmann Saphire
author_sort Kathryn M. Hastie
collection DOAJ
description Summary: Therapeutic antibodies are an important tool in the arsenal against coronavirus infection. However, most antibodies developed early in the pandemic have lost most or all efficacy against newly emergent strains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), particularly those of the Omicron lineage. Here, we report the identification of a panel of vaccinee-derived antibodies that have broad-spectrum neutralization activity. Structural and biochemical characterization of the three broadest-spectrum antibodies reveal complementary footprints and differing requirements for avidity to overcome variant-associated mutations in their binding footprints. In the K18 mouse model of infection, these three antibodies exhibit protective efficacy against BA.1 and BA.2 infection. This study highlights the resilience and vulnerabilities of SARS-CoV-2 antibodies and provides road maps for further development of broad-spectrum therapeutics.
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spelling doaj.art-05a63022e4b143f984c77e5eae90c9db2023-04-21T06:45:13ZengElsevierCell Reports2211-12472023-05-01425112421Potent Omicron-neutralizing antibodies isolated from a patient vaccinated 6 months before Omicron emergenceKathryn M. Hastie0Xiaoying Yu1Fernanda Ana-Sosa-Batiz2Dawid S. Zyla3Stephanie S. Harkins4Chitra Hariharan5Hal Wasserman6Michelle A. Zandonatti7Robyn Miller8Erin Maule9Kenneth Kim10Kristen M. Valentine11Sujan Shresta12Erica Ollmann Saphire13Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USA; Corresponding authorCenter for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USACenter for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USACenter for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USACenter for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USACenter for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USACenter for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USACenter for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USACenter for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USACenter for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USACenter for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USACenter for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USACenter for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USACenter for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USA; Department of Medicine, University of California, San Diego, La Jolla, CA 92038, USA; Corresponding authorSummary: Therapeutic antibodies are an important tool in the arsenal against coronavirus infection. However, most antibodies developed early in the pandemic have lost most or all efficacy against newly emergent strains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), particularly those of the Omicron lineage. Here, we report the identification of a panel of vaccinee-derived antibodies that have broad-spectrum neutralization activity. Structural and biochemical characterization of the three broadest-spectrum antibodies reveal complementary footprints and differing requirements for avidity to overcome variant-associated mutations in their binding footprints. In the K18 mouse model of infection, these three antibodies exhibit protective efficacy against BA.1 and BA.2 infection. This study highlights the resilience and vulnerabilities of SARS-CoV-2 antibodies and provides road maps for further development of broad-spectrum therapeutics.http://www.sciencedirect.com/science/article/pii/S2211124723004321CP: ImmunologyCP: Microbiology
spellingShingle Kathryn M. Hastie
Xiaoying Yu
Fernanda Ana-Sosa-Batiz
Dawid S. Zyla
Stephanie S. Harkins
Chitra Hariharan
Hal Wasserman
Michelle A. Zandonatti
Robyn Miller
Erin Maule
Kenneth Kim
Kristen M. Valentine
Sujan Shresta
Erica Ollmann Saphire
Potent Omicron-neutralizing antibodies isolated from a patient vaccinated 6 months before Omicron emergence
Cell Reports
CP: Immunology
CP: Microbiology
title Potent Omicron-neutralizing antibodies isolated from a patient vaccinated 6 months before Omicron emergence
title_full Potent Omicron-neutralizing antibodies isolated from a patient vaccinated 6 months before Omicron emergence
title_fullStr Potent Omicron-neutralizing antibodies isolated from a patient vaccinated 6 months before Omicron emergence
title_full_unstemmed Potent Omicron-neutralizing antibodies isolated from a patient vaccinated 6 months before Omicron emergence
title_short Potent Omicron-neutralizing antibodies isolated from a patient vaccinated 6 months before Omicron emergence
title_sort potent omicron neutralizing antibodies isolated from a patient vaccinated 6 months before omicron emergence
topic CP: Immunology
CP: Microbiology
url http://www.sciencedirect.com/science/article/pii/S2211124723004321
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