National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
P01 AI144462
United States
Citation
Journal: Cell Rep / Year: 2024 Title: Deep repertoire mining uncovers ultra-broad coronavirus neutralizing antibodies targeting multiple spike epitopes. Authors: Jonathan Hurtado / Thomas F Rogers / David B Jaffe / Bruce A Adams / Sandhya Bangaru / Elijah Garcia / Tazio Capozzola / Terrence Messmer / Pragati Sharma / Ge Song / Nathan Beutler / ...Authors: Jonathan Hurtado / Thomas F Rogers / David B Jaffe / Bruce A Adams / Sandhya Bangaru / Elijah Garcia / Tazio Capozzola / Terrence Messmer / Pragati Sharma / Ge Song / Nathan Beutler / Wanting He / Katharina Dueker / Rami Musharrafieh / Sarah Burbach / Alina Truong / Michael J T Stubbington / Dennis R Burton / Raiees Andrabi / Andrew B Ward / Wyatt J McDonnell / Bryan Briney / Abstract: The development of vaccines and therapeutics that are broadly effective against known and emergent coronaviruses is an urgent priority. We screened the circulating B cell repertoires of COVID-19 ...The development of vaccines and therapeutics that are broadly effective against known and emergent coronaviruses is an urgent priority. We screened the circulating B cell repertoires of COVID-19 survivors and vaccinees to isolate over 9,000 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific monoclonal antibodies (mAbs), providing an expansive view of the SARS-CoV-2-specific Ab repertoire. Among the recovered antibodies was TXG-0078, an N-terminal domain (NTD)-specific neutralizing mAb that recognizes diverse alpha- and beta-coronaviruses. TXG-0078 achieves its exceptional binding breadth while utilizing the same VH1-24 variable gene signature and heavy-chain-dominant binding pattern seen in other NTD-supersite-specific neutralizing Abs with much narrower specificity. We also report CC24.2, a pan-sarbecovirus neutralizing antibody that targets a unique receptor-binding domain (RBD) epitope and shows similar neutralization potency against all tested SARS-CoV-2 variants, including BQ.1.1 and XBB.1.5. A cocktail of TXG-0078 and CC24.2 shows protection in vivo, suggesting their potential use in variant-resistant therapeutic Ab cocktails and as templates for pan-coronavirus vaccine design.
Model: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 300 / Support film - Material: CARBON / Pretreatment - Type: PLASMA CLEANING / Pretreatment - Time: 10 sec.
Vitrification
Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 283 K / Instrument: FEI VITROBOT MARK IV
Details
The spike protein was incubated with a 3-fold molar excess of TXG-0078 Fab for 30 minutes and mixed with 0.04 mM Lauryl maltose neopentyl glycol solution immediately prior to sample deposition.
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Electron microscopy
Microscope
TFS GLACIOS
Image recording
Film or detector model: FEI FALCON IV (4k x 4k) / Detector mode: COUNTING / Number grids imaged: 1 / Number real images: 4257 / Average electron dose: 50.0 e/Å2
Electron beam
Acceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN
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