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- EMDB-41978: GT1.1 SOSIP-CC2 in complex with wk80 polyclonal antibodies from N... -

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Entry
Database: EMDB / ID: EMD-41978
TitleGT1.1 SOSIP-CC2 in complex with wk80 polyclonal antibodies from NHP 8239 (gp120GH, gp41GH/FP, CD4bs, and base epitopes)
Map datamain map
Sample
  • Complex: GT1.1 SOSIP-CC2 in complex with wk80 polyclonal antibodies from NHP 8239 (gp120GH, gp41GH/FP, CD4bs, and base epitopes)
    • Complex: GT1.1 SOSIP-CC2 in complex with wk80 polyclonal antibodies from NHP 8239 (gp120GH, gp41GH/FP, CD4bs, and base epitopes)
Keywordspolyclonal antibodies / non-human primate / germline targeting / HIV / Env / vaccine design / EMPEM / infant macaque / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex
Biological speciesMacaca mulatta (Rhesus monkey) / Human immunodeficiency virus 1
Methodsingle particle reconstruction / negative staining / Resolution: 25.0 Å
AuthorsSewell LM / Ozorowski G / Ward AB
Funding support1 items
OrganizationGrant numberCountry
Bill & Melinda Gates FoundationINV-002916
CitationJournal: Sci Immunol / Year: 2024
Title: Immunization with germ line-targeting SOSIP trimers elicits broadly neutralizing antibody precursors in infant macaques.
Authors: Ashley N Nelson / Xiaoying Shen / Sravani Vekatayogi / Shiyu Zhang / Gabriel Ozorowski / Maria Dennis / Leigh M Sewall / Emma Milligan / Dominique Davis / Kaitlyn A Cross / Yue Chen / Jelle ...Authors: Ashley N Nelson / Xiaoying Shen / Sravani Vekatayogi / Shiyu Zhang / Gabriel Ozorowski / Maria Dennis / Leigh M Sewall / Emma Milligan / Dominique Davis / Kaitlyn A Cross / Yue Chen / Jelle van Schooten / Joshua Eudailey / John Isaac / Saad Memon / Carolyn Weinbaum / Hongmei Gao / Sherry Stanfield-Oakley / Alliyah Byrd / Suni Chutkan / Stella Berendam / Kenneth Cronin / Anila Yasmeen / S Alam / Celia C LaBranche / Kenneth Rogers / Lisa Shirreff / Albert Cupo / Ronald Derking / Francois Villinger / Per Johan Klasse / Guido Ferrari / Wilton B Williams / Michael G Hudgens / Andrew B Ward / David C Montefiori / Koen K A Van Rompay / Kevin Wiehe / John P Moore / Rogier W Sanders / Kristina De Paris / Sallie R Permar /
Abstract: Adolescents are a growing population of people living with HIV. The period between weaning and sexual debut presents a low-risk window for HIV acquisition, making early childhood an ideal time for ...Adolescents are a growing population of people living with HIV. The period between weaning and sexual debut presents a low-risk window for HIV acquisition, making early childhood an ideal time for implementing an immunization regimen. Because the elicitation of broadly neutralizing antibodies (bnAbs) is critical for an effective HIV vaccine, our goal was to assess the ability of a bnAb B cell lineage-designed HIV envelope SOSIP (protein stabilized by a disulfide bond between gp120-gp41-named "SOS"-and an isoleucine-to-proline point mutation-named "IP"-at residue 559) to induce precursor CD4 binding site (CD4bs)-targeting bnAbs in early life. Infant rhesus macaques received either a BG505 SOSIP, based on the infant BG505 transmitted/founder virus, or the CD4bs germ line-targeting BG505 SOSIP GT1.1 ( = 5 per group). Although both strategies induced durable, high-magnitude plasma autologous virus neutralization responses, only GT1.1-immunized infants ( = 3 of 5) exhibited VRC01-like CD4bs bnAb precursor development. Thus, a multidose immunization regimen with bnAb lineage-designed SOSIPs shows promise for inducing early B cell responses with the potential to mature into protective HIV bnAbs before sexual debut.
History
DepositionSep 15, 2023-
Header (metadata) releaseSep 11, 2024-
Map releaseSep 11, 2024-
UpdateSep 11, 2024-
Current statusSep 11, 2024Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_41978.png

Downloads & links

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Map

FileDownload / File: emd_41978.map.gz / Format: CCP4 / Size: 27 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Annotationmain map
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
2.06 Å/pix.
x 192 pix.
= 395.52 Å		2.06 Å/pix.
x 192 pix.
= 395.52 Å		2.06 Å/pix.
x 192 pix.
= 395.52 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 2.06 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.025
Minimum - Maximum-0.02290713 - 0.0588285
Average (Standard dev.)0.00032653572 (±0.0043189954)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions192192192
Spacing192192192
CellA=B=C: 395.52 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: half map 2

Fileemd_41978_half_map_1.map
Annotationhalf map 2
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: half map 1

Fileemd_41978_half_map_2.map
Annotationhalf map 1
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Sample components

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Entire : GT1.1 SOSIP-CC2 in complex with wk80 polyclonal antibodies from N...

EntireName: GT1.1 SOSIP-CC2 in complex with wk80 polyclonal antibodies from NHP 8239 (gp120GH, gp41GH/FP, CD4bs, and base epitopes)
Components
  • Complex: GT1.1 SOSIP-CC2 in complex with wk80 polyclonal antibodies from NHP 8239 (gp120GH, gp41GH/FP, CD4bs, and base epitopes)
    • Complex: GT1.1 SOSIP-CC2 in complex with wk80 polyclonal antibodies from NHP 8239 (gp120GH, gp41GH/FP, CD4bs, and base epitopes)

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Supramolecule #1: GT1.1 SOSIP-CC2 in complex with wk80 polyclonal antibodies from N...

SupramoleculeName: GT1.1 SOSIP-CC2 in complex with wk80 polyclonal antibodies from NHP 8239 (gp120GH, gp41GH/FP, CD4bs, and base epitopes)
type: complex / ID: 1 / Parent: 0 / Details: non-human primate polyclonal antibody Fab
Source (natural)Organism: Macaca mulatta (Rhesus monkey)

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Supramolecule #2: GT1.1 SOSIP-CC2 in complex with wk80 polyclonal antibodies from N...

SupramoleculeName: GT1.1 SOSIP-CC2 in complex with wk80 polyclonal antibodies from NHP 8239 (gp120GH, gp41GH/FP, CD4bs, and base epitopes)
type: complex / ID: 2 / Parent: 1 / Details: GT1.1 SOSIP trimer
Source (natural)Organism: Human immunodeficiency virus 1

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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

Concentration0.03 mg/mL
BufferpH: 7.4
StainingType: NEGATIVE / Material: uranyl formate / Details: 2% w/v

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Electron microscopy

MicroscopeFEI TECNAI SPIRIT
Image recordingFilm or detector model: FEI EAGLE (4k x 4k) / Average electron dose: 25.0 e/Å2
Electron beamAcceleration voltage: 120 kV / Electron source: LAB6
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.5 µm / Nominal defocus min: 1.0 µm / Nominal magnification: 62000
Sample stageSpecimen holder model: SIDE ENTRY, EUCENTRIC
Experimental equipment
Model: Tecnai Spirit / Image courtesy: FEI Company

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Image processing

Startup modelType of model: EMDB MAP
EMDB ID:

20396


Details: low pass filtered to 40 Angstrom
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: 5464
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD

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