Potent Omicron-neutralizing antibodies isolated from a patient vaccinated 6 months before Omicron emergence
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
Affiliations
Kathryn M. Hastie
Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USA; Corresponding author
Xiaoying Yu
Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USA
Fernanda Ana-Sosa-Batiz
Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USA
Dawid S. Zyla
Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USA
Stephanie S. Harkins
Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USA
Chitra Hariharan
Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USA
Hal Wasserman
Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USA
Michelle A. Zandonatti
Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USA
Robyn Miller
Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USA
Erin Maule
Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USA
Kenneth Kim
Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USA
Kristen M. Valentine
Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USA
Sujan Shresta
Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USA
Erica Ollmann Saphire
Center 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 author
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.
