National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
R01 AI146779
United States
Citation
Journal: bioRxiv / Year: 2021 Title: Naive human B cells engage the receptor binding domain of SARS-CoV-2, variants of concern, and related sarbecoviruses. Authors: Jared Feldman / Julia Bals / Clara G Altomare / Kerri St Denis / Evan C Lam / Blake M Hauser / Larance Ronsard / Maya Sangesland / Thalia Bracamonte Moreno / Vintus Okonkwo / Nathania ...Authors: Jared Feldman / Julia Bals / Clara G Altomare / Kerri St Denis / Evan C Lam / Blake M Hauser / Larance Ronsard / Maya Sangesland / Thalia Bracamonte Moreno / Vintus Okonkwo / Nathania Hartojo / Alejandro B Balazs / Goran Bajic / Daniel Lingwood / Aaron G Schmidt / Abstract: Exposure to a pathogen elicits an adaptive immune response aimed to control and eradicate. Interrogating the abundance and specificity of the naive B cell repertoire contributes to understanding how ...Exposure to a pathogen elicits an adaptive immune response aimed to control and eradicate. Interrogating the abundance and specificity of the naive B cell repertoire contributes to understanding how to potentially elicit protective responses. Here, we isolated naive B cells from 8 seronegative human donors targeting the SARS-CoV-2 receptor-binding domain (RBD). Single B cell analysis showed diverse gene usage with no restricted complementarity determining region lengths. We show that recombinant antibodies engage SARS-CoV-2 RBD, circulating variants, and pre-emergent coronaviruses. Representative antibodies signal in a B cell activation assay and can be affinity matured through directed evolution. Structural analysis of a naive antibody in complex with spike shows a conserved mode of recognition shared with infection-induced antibodies. Lastly, both naive and affinity-matured antibodies can neutralize SARS-CoV-2. Understanding the naive repertoire may inform potential responses recognizing variants or emerging coronaviruses enabling the development of pan-coronavirus vaccines aimed at engaging germline responses.
History
Deposition
Jun 22, 2021
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Header (metadata) release
Jun 30, 2021
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Map release
Jun 30, 2021
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Update
Oct 26, 2022
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Current status
Oct 26, 2022
Processing site: RCSB / Status: Released
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Structure visualization
Movie
Surface view with section colored by density value
Organism: Homo sapiens (human) / Recombinant cell: Expi293
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Experimental details
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Structure determination
Method
cryo EM
Processing
single particle reconstruction
Aggregation state
particle
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Sample preparation
Concentration
1 mg/mL
Buffer
pH: 7.5
Grid
Model: UltrAuFoil R0.6/1 / Material: GOLD / Mesh: 400 / Support film - Material: GOLD / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE
Vitrification
Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 293.15 K / Instrument: FEI VITROBOT MARK IV Details: Blot for 3 seconds with blot force 3 before plunge freezing.
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Electron microscopy
Microscope
FEI TITAN KRIOS
Electron beam
Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
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