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TitlePotent Omicron-neutralizing antibodies isolated from a patient vaccinated 6 months before Omicron emergence.
Journal, issue, pagesCell Rep, Vol. 42, Issue 5, Page 112421, Year 2023
Publish dateApr 10, 2023
AuthorsKathryn 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 /
PubMed AbstractTherapeutic 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 ...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.
External linksCell Rep / PubMed:37083327 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution2.57 - 25.0 Å
Structure data

28756

8f0g

EMDB-28756, PDB-8f0g:
Structure of SARS-CoV-2 Omicron BA.1 spike in complex with antibody Fab 1C3
Method: EM (single particle) / Resolution: 3.35 Å

28757

8f0h

EMDB-28757, PDB-8f0h:
Structure of SARS-CoV-2 spike with antibody Fabs 2A10 and 1H2 (Local refinement of the RBD and Fabs 1H2 and 2A10)
Method: EM (single particle) / Resolution: 3.18 Å

EMDB-28763: Negative stain EM map of SARS-CoV-2 D614G Spike in complex with 2A10 IgG
Method: EM (single particle) / Resolution: 17.0 Å

EMDB-28764: Negative stain EM map of SARS-CoV-2 D614G Spike in complex with 4H4 IgG
Method: EM (single particle) / Resolution: 18.0 Å

EMDB-28765: Negative stain EM map of SARS-CoV-2 D614G Spike in complex with 1C3 IgG
Method: EM (single particle) / Resolution: 20.0 Å

EMDB-28769: Negative stain EM map of SARS-CoV-2 Omicron BA.1 Spike in complex with 1C3 IgG
Method: EM (single particle) / Resolution: 25.0 Å

EMDB-28770: Negative stain EM map of SARS-CoV-2 D614G Spike in complex with 2G3 IgG
Method: EM (single particle) / Resolution: 25.0 Å

EMDB-28771: Negative stain EM map of SARS-CoV-2 D614G Spike in complex with 2E6 IgG
Method: EM (single particle) / Resolution: 25.0 Å

EMDB-28772: Negative stain EM map of SARS-CoV-2 D614G Spike in complex with 1H2 Fab
Method: EM (single particle) / Resolution: 20.0 Å

EMDB-28773: Negative stain EM map of SARS-CoV-2 D614G Spike in complex with 1G8 IgG
Method: EM (single particle) / Resolution: 25.0 Å

PDB-8e1g:
SARS-CoV-2 RBD in complex with Omicron-neutralizing antibody 2A10
Method: X-RAY DIFFRACTION / Resolution: 2.57 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • homo sapiens (human)
  • severe acute respiratory syndrome coronavirus 2
KeywordsVIRAL PROTEIN / SARS-CoV-2 / Omicron / antibody / neutralizing / VIRAL PROTEIN/IMMUNE SYSTEM / glycoprotein / immune system / COVID / VIRAL PROTEIN-Immune System complex / coronavirus

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