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- EMDB-27764: Chikungunya VLP in complex with neutralizing Fab 506.A08 (icosahe... -

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Basic information

Entry
Database: EMDB / ID: EMD-27764
TitleChikungunya VLP in complex with neutralizing Fab 506.A08 (icosahedral reconstruction)
Map dataChikungunya VLP in complex with neutralizing Fab 506.A08
Sample
  • Complex: Chikungunya VLP in complex with neutralizing Fab 506.A08
KeywordsAntibody / VIRAL PROTEIN-IMMUNE SYSTEM complex / CSGID / VIRUS LIKE PARTICLE
Biological speciesChikungunya virus strain Senegal 37997
Methodsingle particle reconstruction / cryo EM / Resolution: 4.18 Å
AuthorsAdams LJ / Fremont DH
Funding support United States, 2 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)75N93019C00062 United States
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)HHSN272201700060C United States
CitationJournal: Sci Transl Med / Year: 2023
Title: A chikungunya virus-like particle vaccine induces broadly neutralizing and protective antibodies against alphaviruses in humans.
Authors: Saravanan Raju / Lucas J Adams / James T Earnest / Kelly Warfield / Lo Vang / James E Crowe / Daved H Fremont / Michael S Diamond /
Abstract: Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes epidemics of acute and chronic musculoskeletal disease. Here, we analyzed the human B cell response to a CHIKV-like particle- ...Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes epidemics of acute and chronic musculoskeletal disease. Here, we analyzed the human B cell response to a CHIKV-like particle-adjuvanted vaccine (PXVX0317) from samples obtained from a phase 2 clinical trial in humans (NCT03483961). Immunization with PXVX0317 induced high levels of neutralizing antibody in serum against CHIKV and circulating antigen-specific B cells up to 6 months after immunization. Monoclonal antibodies (mAbs) generated from peripheral blood B cells of three PXVX0317-vaccinated individuals on day 57 after immunization potently neutralized CHIKV infection, and a subset of these inhibited multiple related arthritogenic alphaviruses. Epitope mapping and cryo-electron microscopy defined two broadly neutralizing mAbs that uniquely bind to the apex of the B domain of the E2 glycoprotein. These results demonstrate the inhibitory breadth and activity of the human B cell response induced by the PXVX0317 vaccine against CHIKV and potentially other related alphaviruses.
History
DepositionAug 2, 2022-
Header (metadata) releaseMay 31, 2023-
Map releaseMay 31, 2023-
UpdateMay 31, 2023-
Current statusMay 31, 2023Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_27764.png

Downloads & links

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Map

FileDownload / File: emd_27764.map.gz / Format: CCP4 / Size: 1.9 GB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationChikungunya VLP in complex with neutralizing Fab 506.A08
Voxel sizeX=Y=Z: 1.16 Å
Density
Contour LevelBy AUTHOR: 0.03
Minimum - Maximum-0.10542595 - 0.25812593
Average (Standard dev.)0.0017786194 (±0.020610893)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions800800800
Spacing800800800
CellA=B=C: 928.0 Å
α=β=γ: 90.0 °

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Supplemental data

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Additional map: Unsharpened map

Fileemd_27764_additional_1.map
AnnotationUnsharpened map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: Half map A

Fileemd_27764_half_map_1.map
AnnotationHalf map A
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: Half map B

Fileemd_27764_half_map_2.map
AnnotationHalf map B
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Sample components

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Entire : Chikungunya VLP in complex with neutralizing Fab 506.A08

EntireName: Chikungunya VLP in complex with neutralizing Fab 506.A08
Components
  • Complex: Chikungunya VLP in complex with neutralizing Fab 506.A08

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Supramolecule #1: Chikungunya VLP in complex with neutralizing Fab 506.A08

SupramoleculeName: Chikungunya VLP in complex with neutralizing Fab 506.A08
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#5
Source (natural)Organism: Chikungunya virus strain Senegal 37997

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

BufferpH: 7.4
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 2.2 µm / Nominal defocus min: 0.7000000000000001 µm / Nominal magnification: 59000
Image recordingFilm or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 38.25 e/Å2
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Startup modelType of model: INSILICO MODEL
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
Final reconstructionResolution.type: BY AUTHOR / Resolution: 4.18 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 27321
FSC plot (resolution estimation)

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