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- EMDB-27039: SARS-CoV-2 S protein mix in complex with Novavax NHP 36057 polycl... -

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Basic information

Entry
Database: EMDB / ID: EMD-27039
TitleSARS-CoV-2 S protein mix in complex with Novavax NHP 36057 polyclonal Fab
Map datarefined map of SARS-CoV-2 ancestral spike mix with Novavax NHP 36057 fabs (C1 symmetry)
Sample
  • Complex: SARS-CoV-2 S protein mix in complex with Novavax NHP 36057 polyclonal Fab
    • Complex: SARS-CoV-2 S protein
    • Complex: Novavax NHP 36057 Polyclonal Fab
Biological speciesSevere acute respiratory syndrome coronavirus 2 / Macaca mulatta (Rhesus monkey)
Methodsingle particle reconstruction / negative staining / Resolution: 25.0 Å
AuthorsJackson AM / Bangaru S / Ward AB
Funding support United States, 1 items
OrganizationGrant numberCountry
Bill & Melinda Gates FoundationINV-004923 United States
CitationJournal: Immunity / Year: 2022
Title: Antibodies from primary humoral responses modulate the recruitment of naive B cells during secondary responses.
Authors: Jeroen M J Tas / Ja-Hyun Koo / Ying-Cing Lin / Zhenfei Xie / Jon M Steichen / Abigail M Jackson / Blake M Hauser / Xuesong Wang / Christopher A Cottrell / Jonathan L Torres / John E Warner / ...Authors: Jeroen M J Tas / Ja-Hyun Koo / Ying-Cing Lin / Zhenfei Xie / Jon M Steichen / Abigail M Jackson / Blake M Hauser / Xuesong Wang / Christopher A Cottrell / Jonathan L Torres / John E Warner / Kathrin H Kirsch / Stephanie R Weldon / Bettina Groschel / Bartek Nogal / Gabriel Ozorowski / Sandhya Bangaru / Nicole Phelps / Yumiko Adachi / Saman Eskandarzadeh / Michael Kubitz / Dennis R Burton / Daniel Lingwood / Aaron G Schmidt / Usha Nair / Andrew B Ward / William R Schief / Facundo D Batista /
Abstract: Vaccines generate high-affinity antibodies by recruiting antigen-specific B cells to germinal centers (GCs), but the mechanisms governing the recruitment to GCs on secondary challenges remain unclear. ...Vaccines generate high-affinity antibodies by recruiting antigen-specific B cells to germinal centers (GCs), but the mechanisms governing the recruitment to GCs on secondary challenges remain unclear. Here, using preclinical SARS-CoV and HIV mouse models, we demonstrated that the antibodies elicited during primary humoral responses shaped the naive B cell recruitment to GCs during secondary exposures. The antibodies from primary responses could either enhance or, conversely, restrict the GC participation of naive B cells: broad-binding, low-affinity, and low-titer antibodies enhanced recruitment, whereas, by contrast, the high titers of high-affinity, mono-epitope-specific antibodies attenuated cognate naive B cell recruitment. Thus, the directionality and intensity of that effect was determined by antibody concentration, affinity, and epitope specificity. Circulating antibodies can, therefore, be important determinants of antigen immunogenicity. Future vaccines may need to overcome-or could, alternatively, leverage-the effects of circulating primary antibodies on subsequent naive B cell recruitment.
History
DepositionMay 20, 2022-
Header (metadata) releaseSep 7, 2022-
Map releaseSep 7, 2022-
UpdateOct 26, 2022-
Current statusOct 26, 2022Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

Downloads & links

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Map

FileDownload / File: emd_27039.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Annotationrefined map of SARS-CoV-2 ancestral spike mix with Novavax NHP 36057 fabs (C1 symmetry)
Voxel sizeX=Y=Z: 2.06 Å
Density
Contour LevelBy AUTHOR: 0.01
Minimum - Maximum-0.016613951 - 0.06176355
Average (Standard dev.)-0.00023906885 (±0.0029881562)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions256256256
Spacing256256256
CellA=B=C: 527.36 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: half map of SARS-CoV-2 ancestral spike mix with...

Fileemd_27039_half_map_1.map
Annotationhalf map of SARS-CoV-2 ancestral spike mix with Novavax NHP 36057 fabs (C1 symmetry)
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Half map: half map of SARS-CoV-2 ancestral spike mix with...

Fileemd_27039_half_map_2.map
Annotationhalf map of SARS-CoV-2 ancestral spike mix with Novavax NHP 36057 fabs (C1 symmetry)
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Sample components

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Entire : SARS-CoV-2 S protein mix in complex with Novavax NHP 36057 polycl...

EntireName: SARS-CoV-2 S protein mix in complex with Novavax NHP 36057 polyclonal Fab
Components
  • Complex: SARS-CoV-2 S protein mix in complex with Novavax NHP 36057 polyclonal Fab
    • Complex: SARS-CoV-2 S protein
    • Complex: Novavax NHP 36057 Polyclonal Fab

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Supramolecule #1: SARS-CoV-2 S protein mix in complex with Novavax NHP 36057 polycl...

SupramoleculeName: SARS-CoV-2 S protein mix in complex with Novavax NHP 36057 polyclonal Fab
type: complex / Chimera: Yes / ID: 1 / Parent: 0

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Supramolecule #2: SARS-CoV-2 S protein

SupramoleculeName: SARS-CoV-2 S protein / type: complex / Chimera: Yes / ID: 2 / Parent: 1
Source (natural)Organism: Severe acute respiratory syndrome coronavirus 2
Recombinant expressionOrganism: Homo sapiens (human)

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Supramolecule #3: Novavax NHP 36057 Polyclonal Fab

SupramoleculeName: Novavax NHP 36057 Polyclonal Fab / type: complex / Chimera: Yes / ID: 3 / Parent: 1
Source (natural)Organism: Macaca mulatta (Rhesus monkey)
Recombinant expressionOrganism: Homo sapiens (human)

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Experimental details

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Structure determination

Methodnegative staining
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

BufferpH: 7.4
StainingType: NEGATIVE / Material: uranyl formate

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Electron microscopy

MicroscopeFEI TECNAI SPIRIT
Electron beamAcceleration voltage: 120 kV / Electron source: LAB6
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 2.0 µm / Nominal defocus min: 1.0 µm
Image recordingFilm or detector model: FEI EAGLE (4k x 4k) / Average electron dose: 50.0 e/Å2
Experimental equipment
Model: Tecnai Spirit / Image courtesy: FEI Company

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Image processing

Startup modelType of model: PDB ENTRY
PDB model - PDB ID:
Initial angle assignmentType: OTHER
Final angle assignmentType: OTHER
Final reconstructionResolution.type: BY AUTHOR / Resolution: 25.0 Å / Resolution method: FSC 0.5 CUT-OFF / Number images used: 89236

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