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...
Main Authors: | , , , , , , , , , , , , , |
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Format: | Article |
Language: | English |
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Elsevier
2023-05-01
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Series: | Cell Reports |
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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. |
first_indexed | 2024-04-09T16:53:05Z |
format | Article |
id | doaj.art-05a63022e4b143f984c77e5eae90c9db |
institution | Directory Open Access Journal |
issn | 2211-1247 |
language | English |
last_indexed | 2024-04-09T16:53:05Z |
publishDate | 2023-05-01 |
publisher | Elsevier |
record_format | Article |
series | Cell Reports |
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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