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- EMDB-14896: NHP MCM04 wk26 base pAb in complex with ConM SOSIP -

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Basic information

Entry
Database: EMDB / ID: EMD-14896
TitleNHP MCM04 wk26 base pAb in complex with ConM SOSIP
Map data
Sample
  • Complex: NHP MCM04 wk26 base pAb in complex with ConM SOSIP
Biological speciesMacaca fascicularis (crab-eating macaque)
Methodsingle particle reconstruction / negative staining / Resolution: 25.0 Å
Authorsvan Schooten J / Ward AB
Funding support United States, 3 items
OrganizationGrant numberCountry
Bill & Melinda Gates FoundationOPP1115782 United States
Bill & Melinda Gates FoundationINV-002916 United States
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)AI110657 United States
CitationJournal: NPJ Vaccines / Year: 2022
Title: Fine-mapping the immunodominant antibody epitopes on consensus sequence-based HIV-1 envelope trimer vaccine candidates.
Authors: E I M M Reiss / M M van Haaren / J van Schooten / M A F Claireaux / P Maisonnasse / A Antanasijevic / J D Allen / I Bontjer / J L Torres / W-H Lee / G Ozorowski / N Vázquez Bernat / M Kaduk ...Authors: E I M M Reiss / M M van Haaren / J van Schooten / M A F Claireaux / P Maisonnasse / A Antanasijevic / J D Allen / I Bontjer / J L Torres / W-H Lee / G Ozorowski / N Vázquez Bernat / M Kaduk / Y Aldon / J A Burger / H Chawla / A Aartse / M Tolazzi / H Gao / P Mundsperger / M Crispin / D C Montefiori / G B Karlsson Hedestam / G Scarlatti / A B Ward / R Le Grand / R Shattock / N Dereuddre-Bosquet / R W Sanders / M J van Gils /
Abstract: The HIV-1 envelope glycoprotein (Env) trimer is the key target for vaccines aimed at inducing neutralizing antibodies (NAbs) against HIV-1. The clinical candidate immunogen ConM SOSIP.v7 is a ...The HIV-1 envelope glycoprotein (Env) trimer is the key target for vaccines aimed at inducing neutralizing antibodies (NAbs) against HIV-1. The clinical candidate immunogen ConM SOSIP.v7 is a stabilized native-like HIV-1 Env trimer based on an artificial consensus sequence of all HIV-1 isolates in group M. In preclinical studies ConM SOSIP.v7 trimers induced strong autologous NAb responses in non-human primates (NHPs). To fine-map these responses, we isolated monoclonal antibodies (mAbs) from six cynomolgus macaques that were immunized three times with ConM SOSIP.v7 protein and boosted twice with the closely related ConSOSL.UFO.664 immunogen. A total of 40 ConM and/or ConS-specific mAbs were isolated, of which 18 were retrieved after the three ConM SOSIP.v7 immunizations and 22 after the two immunizations with ConSOSL.UFO.664. 22 mAbs (55%) neutralized the ConM and/or ConS virus. Cross-neutralization of ConS virus by approximately one-third of the mAbs was seen prior to ConSOSL.UFO.664 immunization, albeit with modest potency. Neutralizing antibodies predominantly targeted the V1 and V2 regions of the immunogens, with an apparent extension towards the V3 region. Thus, the V1V2V3 region is immunodominant in the potent NAb response elicited by two consensus sequence native-like HIV-1 Env immunogens. Immunization with these soluble consensus Env proteins also elicited non-neutralizing mAbs targeting the trimer base. These results inform the use and improvement of consensus-based trimer immunogens in combinatorial vaccine strategies.
History
DepositionMay 4, 2022-
Header (metadata) releaseDec 7, 2022-
Map releaseDec 7, 2022-
UpdateDec 7, 2022-
Current statusDec 7, 2022Processing site: PDBe / Status: Released

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Structure visualization

Supplemental images

Downloads & links

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Map

FileDownload / File: emd_14896.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.)
1.77 Å/pix.
x 192 pix.
= 339.84 Å
1.77 Å/pix.
x 192 pix.
= 339.84 Å
1.77 Å/pix.
x 192 pix.
= 339.84 Å

Surface

Projections

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Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.77 Å
Density
Contour LevelBy AUTHOR: 0.015
Minimum - Maximum-0.03193973 - 0.11547185
Average (Standard dev.)2.0231031e-05 (±0.0043832446)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions192192192
Spacing192192192
CellA=B=C: 339.84 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #1

Fileemd_14896_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Half map: #2

Fileemd_14896_half_map_2.map
Projections & Slices
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Sample components

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Entire : NHP MCM04 wk26 base pAb in complex with ConM SOSIP

EntireName: NHP MCM04 wk26 base pAb in complex with ConM SOSIP
Components
  • Complex: NHP MCM04 wk26 base pAb in complex with ConM SOSIP

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Supramolecule #1: NHP MCM04 wk26 base pAb in complex with ConM SOSIP

SupramoleculeName: NHP MCM04 wk26 base pAb in complex with ConM SOSIP / type: complex / Chimera: Yes / ID: 1 / Parent: 0
Source (natural)Organism: Macaca fascicularis (crab-eating macaque)

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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 F20
Electron beamAcceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 1.5 µm / Nominal defocus min: 1.0 µm
Image recordingFilm or detector model: TVIPS TEMCAM-F416 (4k x 4k) / Average electron dose: 25.0 e/Å2
Experimental equipment
Model: Tecnai F20 / Image courtesy: FEI Company

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Image processing

Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
Final reconstructionApplied symmetry - Point group: C1 (asymmetric) / Resolution.type: BY AUTHOR / Resolution: 25.0 Å / Resolution method: FSC 0.5 CUT-OFF / Software - Name: RELION (ver. 3.0) / Number images used: 97835

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