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- EMDB-9138: HIV-1 vaccine elicited Fab BDA1 in complex with the HIV Env trime... -

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Basic information

Entry
Database: EMDB / ID: EMD-9138
TitleHIV-1 vaccine elicited Fab BDA1 in complex with the HIV Env trimer BG505 SOSIPv5.2
Map data
SampleHIV-1 vaccine elicited Fab BDA1 in complex with the HIV Env trimer BG505 SOSIPv5.2:
SOSIP trimer / BDA1 Fab / (BG505 SOSIPv5.2 ...) x 2 / BDA1 Fab heavy chain / BDA1 Fab light chain
Biological speciesHuman immunodeficiency virus 1 / Homo sapiens (human) / Macaca mulatta (Rhesus monkey)
Methodsingle particle reconstruction / Resolution: 21 Å
AuthorsCottrell CA / Ward AB
CitationJournal: Cell / Year: 2019
Title: Slow Delivery Immunization Enhances HIV Neutralizing Antibody and Germinal Center Responses via Modulation of Immunodominance.
Authors: Kimberly M Cirelli / Diane G Carnathan / Bartek Nogal / Jacob T Martin / Oscar L Rodriguez / Amit A Upadhyay / Chiamaka A Enemuo / Etse H Gebru / Yury Choe / Federico Viviano / Catherine Nakao / Matthias G Pauthner / Samantha Reiss / Christopher A Cottrell / Melissa L Smith / Raiza Bastidas / William Gibson / Amber N Wolabaugh / Mariane B Melo / Benjamin Cossette / Venkatesh Kumar / Nirav B Patel / Talar Tokatlian / Sergey Menis / Daniel W Kulp / Dennis R Burton / Ben Murrell / William R Schief / Steven E Bosinger / Andrew B Ward / Corey T Watson / Guido Silvestri / Darrell J Irvine / Shane Crotty /
Abstract: Conventional immunization strategies will likely be insufficient for the development of a broadly neutralizing antibody (bnAb) vaccine for HIV or other difficult pathogens because of the ...Conventional immunization strategies will likely be insufficient for the development of a broadly neutralizing antibody (bnAb) vaccine for HIV or other difficult pathogens because of the immunological hurdles posed, including B cell immunodominance and germinal center (GC) quantity and quality. We found that two independent methods of slow delivery immunization of rhesus monkeys (RMs) resulted in more robust T follicular helper (T) cell responses and GC B cells with improved Env-binding, tracked by longitudinal fine needle aspirates. Improved GCs correlated with the development of >20-fold higher titers of autologous nAbs. Using a new RM genomic immunoglobulin locus reference, we identified differential IgV gene use between immunization modalities. Ab mapping demonstrated targeting of immunodominant non-neutralizing epitopes by conventional bolus-immunized animals, whereas slow delivery-immunized animals targeted a more diverse set of epitopes. Thus, alternative immunization strategies can enhance nAb development by altering GCs and modulating the immunodominance of non-neutralizing epitopes.
History
DepositionSep 27, 2018-
Header (metadata) releaseOct 31, 2018-
Map releaseMay 29, 2019-
UpdateMay 29, 2019-
Current statusMay 29, 2019Processing site: RCSB / Status: Released

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Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 0.01669377
  • Imaged by UCSF Chimera
  • Download
  • Surface view colored by cylindrical radius
  • Surface level: 0.01669377
  • Imaged by UCSF Chimera
  • Download
Movie viewer
Structure viewerEM map:
SurfViewMolmilJmol/JSmol
Supplemental images

Downloads & links

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Map

FileDownload / File: emd_9138.map.gz / Format: CCP4 / Size: 27 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.98 Å/pix.
x 192 pix.
= 380.16 Å
1.98 Å/pix.
x 192 pix.
= 380.16 Å
1.98 Å/pix.
x 192 pix.
= 380.16 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.98 Å
Density
Contour LevelBy AUTHOR: 0.012 / Movie #1: 0.0166938
Minimum - Maximum-0.04054257 - 0.14626986
Average (Standard dev.)-0.00003215719 (±0.004640977)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions192192192
Spacing192192192
CellA=B=C: 380.16 Å
α=β=γ: 90.0 °

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z1.981.981.98
M x/y/z192192192
origin x/y/z0.0000.0000.000
length x/y/z380.160380.160380.160
α/β/γ90.00090.00090.000
MAP C/R/S123
start NC/NR/NS000
NC/NR/NS192192192
D min/max/mean-0.0410.146-0.000

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Supplemental data

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Sample components

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Entire HIV-1 vaccine elicited Fab BDA1 in complex with the HIV Env trime...

EntireName: HIV-1 vaccine elicited Fab BDA1 in complex with the HIV Env trimer BG505 SOSIPv5.2
Number of components: 7

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Component #1: protein, HIV-1 vaccine elicited Fab BDA1 in complex with the HIV ...

ProteinName: HIV-1 vaccine elicited Fab BDA1 in complex with the HIV Env trimer BG505 SOSIPv5.2
Recombinant expression: No

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Component #2: protein, SOSIP trimer

ProteinName: SOSIP trimer / Recombinant expression: No
SourceSpecies: Human immunodeficiency virus 1

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Component #3: protein, BDA1 Fab

ProteinName: BDA1 Fab / Recombinant expression: No
SourceSpecies: Homo sapiens (human)

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Component #4: protein, BG505 SOSIPv5.2 gp120

ProteinName: BG505 SOSIPv5.2 gp120 / Recombinant expression: No
SourceSpecies: Human immunodeficiency virus 1
Source (engineered)Expression System: Homo sapiens (human)

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Component #5: protein, BG505 SOSIPv5.2 gp41

ProteinName: BG505 SOSIPv5.2 gp41 / Recombinant expression: No
SourceSpecies: Human immunodeficiency virus 1
Source (engineered)Expression System: Homo sapiens (human)

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Component #6: protein, BDA1 Fab heavy chain

ProteinName: BDA1 Fab heavy chain / Recombinant expression: No
SourceSpecies: Macaca mulatta (Rhesus monkey)
Source (engineered)Expression System: Homo sapiens (human)

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Component #7: protein, BDA1 Fab light chain

ProteinName: BDA1 Fab light chain / Recombinant expression: No
SourceSpecies: Macaca mulatta (Rhesus monkey)
Source (engineered)Expression System: Homo sapiens (human)

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Experimental details

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Sample preparation

SpecimenSpecimen state: Particle
Sample solutionpH: 7.4
VitrificationCryogen name: NONE

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Electron microscopy imaging

Experimental equipment
Model: Talos Arctica / Image courtesy: FEI Company
ImagingMicroscope: FEI TALOS ARCTICA
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Electron dose: 25 e/Å2 / Illumination mode: FLOOD BEAM
LensImaging mode: BRIGHT FIELD
Specimen HolderModel: SIDE ENTRY, EUCENTRIC
CameraDetector: FEI CETA (4k x 4k)

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Image acquisition

Image acquisitionSampling size: 14 µm

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Image processing

ProcessingMethod: single particle reconstruction / Applied symmetry: C1 (asymmetric) / Number of projections: 15024
3D reconstructionSoftware: RELION / Resolution: 21 Å / Resolution method: FSC 0.5 CUT-OFF

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