tetano
Editor, Senior Moderator
Cell Rep
. 2023 Apr 10;42(5):112421.
doi: 10.1016/j.celrep.2023.112421. Online ahead of print.
Potent Omicron-neutralizing antibodies isolated from a patient vaccinated 6 months before Omicron emergence
Kathryn M Hastie[SUP] 1 [/SUP], Xiaoying Yu[SUP] 2 [/SUP], Fernanda Ana-Sosa-Batiz[SUP] 2 [/SUP], Dawid S Zyla[SUP] 2 [/SUP], Stephanie S Harkins[SUP] 2 [/SUP], Chitra Hariharan[SUP] 2 [/SUP], Hal Wasserman[SUP] 2 [/SUP], Michelle A Zandonatti[SUP] 2 [/SUP], Robyn Miller[SUP] 2 [/SUP], Erin Maule[SUP] 2 [/SUP], Kenneth Kim[SUP] 2 [/SUP], Kristen M Valentine[SUP] 2 [/SUP], Sujan Shresta[SUP] 2 [/SUP], Erica Ollmann Saphire[SUP] 3 [/SUP]
Affiliations
Abstract
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.
Keywords: COVID-19; CP: Immunology; CP: Microbiology; Omicron; SARS-CoV-2; antibodies; bivalent antibody binding; coronavirus; cryo-EM; neutralization.
. 2023 Apr 10;42(5):112421.
doi: 10.1016/j.celrep.2023.112421. Online ahead of print.
Potent Omicron-neutralizing antibodies isolated from a patient vaccinated 6 months before Omicron emergence
Kathryn M Hastie[SUP] 1 [/SUP], Xiaoying Yu[SUP] 2 [/SUP], Fernanda Ana-Sosa-Batiz[SUP] 2 [/SUP], Dawid S Zyla[SUP] 2 [/SUP], Stephanie S Harkins[SUP] 2 [/SUP], Chitra Hariharan[SUP] 2 [/SUP], Hal Wasserman[SUP] 2 [/SUP], Michelle A Zandonatti[SUP] 2 [/SUP], Robyn Miller[SUP] 2 [/SUP], Erin Maule[SUP] 2 [/SUP], Kenneth Kim[SUP] 2 [/SUP], Kristen M Valentine[SUP] 2 [/SUP], Sujan Shresta[SUP] 2 [/SUP], Erica Ollmann Saphire[SUP] 3 [/SUP]
Affiliations
- PMID: 37083327
- DOI: 10.1016/j.celrep.2023.112421
Abstract
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.
Keywords: COVID-19; CP: Immunology; CP: Microbiology; Omicron; SARS-CoV-2; antibodies; bivalent antibody binding; coronavirus; cryo-EM; neutralization.