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- EMDB-41871: BG505.664 Env SOSIP in complex with polyclonal antibodies from NH... -

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Basic information

Entry
Database: EMDB / ID: EMD-41871
TitleBG505.664 Env SOSIP in complex with polyclonal antibodies from NHP 8147 (C3/V5, V1/V2/V3 apex, gp41 glycan hole/fusion peptide and trimer base epitopes)
Map dataEM map
Sample
  • Complex: BG505.664 Env SOSIP in complex with polyclonal antibodies from NHP 8147 (C3/V5, V1/V2/V3 apex, gp41 glycan hole/fusion peptide and trimer base epitopes)
    • Complex: Polyclonal antibodies from NHP 8147
KeywordsHIV / Fab / polyclonal / EMPEM / NHP / non-human primate / VIRAL PROTEIN
Biological speciesHuman immunodeficiency virus 1 / Macaca (macaques)
Methodsingle particle reconstruction / negative staining / Resolution: 25.0 Å
AuthorsZhang S / Ward AB
Funding support United States, 1 items
OrganizationGrant numberCountry
Bill & Melinda Gates FoundationINV-002916 United States
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 8, 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

Downloads & links

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Map

FileDownload / File: emd_41871.map.gz / Format: CCP4 / Size: 3.8 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationEM map
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
4.13 Å/pix.
x 100 pix.
= 413. Å
4.13 Å/pix.
x 100 pix.
= 413. Å
4.13 Å/pix.
x 100 pix.
= 413. Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 4.13 Å
Density
Contour LevelBy AUTHOR: 0.02
Minimum - Maximum-0.10764704 - 0.22613327
Average (Standard dev.)-0.00045005293 (±0.0107586235)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions100100100
Spacing100100100
CellA=B=C: 413.0 Å
α=β=γ: 90.0 °

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Supplemental data

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Sample components

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Entire : BG505.664 Env SOSIP in complex with polyclonal antibodies from NH...

EntireName: BG505.664 Env SOSIP in complex with polyclonal antibodies from NHP 8147 (C3/V5, V1/V2/V3 apex, gp41 glycan hole/fusion peptide and trimer base epitopes)
Components
  • Complex: BG505.664 Env SOSIP in complex with polyclonal antibodies from NHP 8147 (C3/V5, V1/V2/V3 apex, gp41 glycan hole/fusion peptide and trimer base epitopes)
    • Complex: Polyclonal antibodies from NHP 8147

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Supramolecule #1: BG505.664 Env SOSIP in complex with polyclonal antibodies from NH...

SupramoleculeName: BG505.664 Env SOSIP in complex with polyclonal antibodies from NHP 8147 (C3/V5, V1/V2/V3 apex, gp41 glycan hole/fusion peptide and trimer base epitopes)
type: complex / ID: 1 / Parent: 0 / Details: HIV-1 Envelope (Env) trimer BG505.664
Source (natural)Organism: Human immunodeficiency virus 1

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Supramolecule #2: Polyclonal antibodies from NHP 8147

SupramoleculeName: Polyclonal antibodies from NHP 8147 / type: complex / ID: 2 / Parent: 1
Source (natural)Organism: Macaca (macaques)

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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
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 opticsC2 aperture diameter: 70.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.5 µm / Nominal defocus min: 1.0 µm
Sample stageCooling holder cryogen: NITROGEN
Experimental equipment
Model: Tecnai Spirit / Image courtesy: FEI Company

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Image processing

Particle selectionNumber selected: 118751
Startup modelType of model: EMDB MAP
EMDB ID:

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: 1932
Initial angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: RELION
Final angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: RELION

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