National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
U19 AI142790
United States
Defense Threat Reduction Agency (DTRA)
HDTRA1-13-1-0034
United States
Citation
Journal: Cell / Year: 2020 Title: Human Antibodies Protect against Aerosolized Eastern Equine Encephalitis Virus Infection. Authors: Lauren E Williamson / Theron Gilliland / Pramod K Yadav / Elad Binshtein / Robin Bombardi / Nurgun Kose / Rachel S Nargi / Rachel E Sutton / Clarissa L Durie / Erica Armstrong / Robert H ...Authors: Lauren E Williamson / Theron Gilliland / Pramod K Yadav / Elad Binshtein / Robin Bombardi / Nurgun Kose / Rachel S Nargi / Rachel E Sutton / Clarissa L Durie / Erica Armstrong / Robert H Carnahan / Lauren M Walker / Arthur S Kim / Julie M Fox / Michael S Diamond / Melanie D Ohi / William B Klimstra / James E Crowe / Abstract: Eastern equine encephalitis virus (EEEV) is one of the most virulent viruses endemic to North America. No licensed vaccines or antiviral therapeutics are available to combat this infection, which has ...Eastern equine encephalitis virus (EEEV) is one of the most virulent viruses endemic to North America. No licensed vaccines or antiviral therapeutics are available to combat this infection, which has recently shown an increase in human cases. Here, we characterize human monoclonal antibodies (mAbs) isolated from a survivor of natural EEEV infection with potent (<20 pM) inhibitory activity of EEEV. Cryo-electron microscopy reconstructions of two highly neutralizing mAbs, EEEV-33 and EEEV-143, were solved in complex with chimeric Sindbis/EEEV virions to 7.2 Å and 8.3 Å, respectively. The mAbs recognize two distinct antigenic sites that are critical for inhibiting viral entry into cells. EEEV-33 and EEEV-143 protect against disease following stringent lethal aerosol challenge of mice with highly pathogenic EEEV. These studies provide insight into the molecular basis for the neutralizing human antibody response against EEEV and can facilitate development of vaccines and candidate antibody therapeutics.
History
Deposition
Jul 6, 2020
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Header (metadata) release
Dec 23, 2020
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Map release
Dec 23, 2020
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Update
Jan 13, 2021
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Current status
Jan 13, 2021
Processing site: RCSB / Status: Released
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Structure visualization
Movie
Surface view with section colored by density value
Cryogen name: ETHANE / Chamber humidity: 100 % / Instrument: FEI VITROBOT MARK IV / Details: blot time 2.5s blot force 9.
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Electron microscopy
Microscope
FEI TITAN KRIOS
Image recording
Film or detector model: FEI FALCON III (4k x 4k) / Detector mode: COUNTING / Digitization - Sampling interval: 0.8608 µm / Number grids imaged: 1 / Number real images: 1745 / Average electron dose: 30.0 e/Å2
Electron beam
Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron optics
Illumination mode: OTHER / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 2.0 µm / Nominal defocus min: 0.8 µm / Nominal magnification: 96000
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