Potent, Omicron-Neutralizing Antibodies Isolated From a Patient Vaccinated 6 Months Before Omicron Emergence

• DOI: 10.2139/ssrn.4327436
• Publication Date: 2023-02-01T17:52:24Z
• Authors: Kathryn Hastie; Xiaoying Yu; Fernanda Ana Sos...; Dawid Zyla; Stephanie S. Har...; Chitra Hariharan; Hal Wasserman; Michelle Zandonatti; Robyn Miller; Erin Maule; Kenneth Kim; Kristen Valentine; Sujan Shresta; Erica Ollmann Sa...
• Keywords: 0301 basic medicine; QH301-705.5; SARS-CoV-2; CP: Microbiology; COVID-19; CP: Immunology; Antibodies, Viral; Antibodies, Neutralizing; Article; 3. Good health; Mice; 03 medical and health sciences; Animals; Biology (General); Broadly Neutralizing Antibodies

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.