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- EMDB-70190: HIV-1 N332-GT5 SOSIP in complex with mouse polyclonal antibodies ... -

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Basic information

Entry
Database: EMDB / ID: EMD-70190
TitleHIV-1 N332-GT5 SOSIP in complex with mouse polyclonal antibodies (V3-glycan epitope) following mRNA multi antigen prime
Map datamain map
Sample
  • Complex: HIV-1 N332-GT5 SOSIP in complex with mouse polyclonal antibodies (V3-glycan epitope) following mRNA multi antigen prime
KeywordsEMPEM / BG18 / germline targeting / HIV-1 / VIRAL PROTEIN
Biological speciesMus musculus (house mouse)
Methodsingle particle reconstruction / negative staining / Resolution: 30.0 Å
AuthorsTorres JL / Ozorowski G / Ward AB
Funding support United States, 1 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)UM1 AI144462 United States
CitationJournal: Sci Immunol / Year: 2025
Title: Simultaneous priming of HIV broadly neutralizing antibody precursors to multiple epitopes by germline-targeting mRNA-LNP immunogens in mouse models.
Authors: Zhenfei Xie / Xuesong Wang / Yu Yan / Jon M Steichen / Krystal M Ma / Christopher A Cottrell / Eleonora Melzi / Maria Bottermann / Paula Maldonado Villavicencio / Kimmo Rantalainen / Torben ...Authors: Zhenfei Xie / Xuesong Wang / Yu Yan / Jon M Steichen / Krystal M Ma / Christopher A Cottrell / Eleonora Melzi / Maria Bottermann / Paula Maldonado Villavicencio / Kimmo Rantalainen / Torben Schiffner / John E Warner / Stephanie R Weldon / Thavaleak Prum / Jordan R Ellis-Pugh / Jonathan L Torres / Abigail M Jackson / Claudia T Flynn / Gabriel Ozorowski / Sunny Himansu / Andrea Carfi / Andrew B Ward / Usha Nair / William R Schief / Facundo D Batista /
Abstract: Germline-targeting is a promising approach to HIV vaccine development that begins with the elicitation of precursors to broadly neutralizing antibodies (bnAbs), but it remains unclear whether ...Germline-targeting is a promising approach to HIV vaccine development that begins with the elicitation of precursors to broadly neutralizing antibodies (bnAbs), but it remains unclear whether simultaneous elicitation of precursors to multiple epitopes on the HIV envelope (Env) would be inhibited by competition. This study used preclinical mouse models with physiologically relevant frequencies of bnAb precursor-bearing B cells to compare precursor elicitation by coadministration of multiple protein or mRNA lipid nanoparticle (mRNA-LNP) germline-targeting immunogens. These immunogens activate multiple bnAb precursor classes targeting distinct epitopes on Env but with evidence of potential competition. Simultaneous delivery of immunogens encoded by mRNA-LNPs, however, drove maturation across different precursor frequencies and immunogen doses. Furthermore, administration of a cocktail of mRNA-LNP immunogens (N332-GT5 gp151, ApexGT5 gp151, eOD-GT8 60mer, and 10E8-GT12 24mer) led to balanced activation of four distinct bnAb precursor classes, indicating that multiepitope HIV bnAb precursor priming might be successfully implemented in humans but might be immunogen dependent.
History
DepositionApr 14, 2025-
Header (metadata) releaseNov 12, 2025-
Map releaseNov 12, 2025-
UpdateNov 12, 2025-
Current statusNov 12, 2025Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_70190.png

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Map

FileDownload / File: emd_70190.map.gz / Format: CCP4 / Size: 27 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Annotationmain map
Projections & slices

Image control

Size
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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

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Images are generated by Spider.

Voxel sizeX=Y=Z: 2.06 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.012
Minimum - Maximum-0.04219925 - 0.11771979
Average (Standard dev.)-0.00016264827 (±0.004419355)
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 A

Fileemd_70190_half_map_1.map
Annotationhalf map A
Projections & Slices
AxesZYX

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Slices (1/2)
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Histogram

Histogram (log scale)

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Half map: half map B

Fileemd_70190_half_map_2.map
Annotationhalf map B
Projections & Slices
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Histogram

Histogram (log scale)

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Sample components

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Entire : HIV-1 N332-GT5 SOSIP in complex with mouse polyclonal antibodies ...

EntireName: HIV-1 N332-GT5 SOSIP in complex with mouse polyclonal antibodies (V3-glycan epitope) following mRNA multi antigen prime
Components
  • Complex: HIV-1 N332-GT5 SOSIP in complex with mouse polyclonal antibodies (V3-glycan epitope) following mRNA multi antigen prime

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Supramolecule #1: HIV-1 N332-GT5 SOSIP in complex with mouse polyclonal antibodies ...

SupramoleculeName: HIV-1 N332-GT5 SOSIP in complex with mouse polyclonal antibodies (V3-glycan epitope) following mRNA multi antigen prime
type: complex / ID: 1 / Parent: 0
Details: Mouse serum IgG isolated and digested to Fab prior to complexing with N332-GT5 antigen
Source (natural)Organism: Mus musculus (house mouse)

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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

Concentration0.02 mg/mL
BufferpH: 7.4
StainingType: NEGATIVE / Material: uranyl formate / Details: 2% uranyl formate, 45 s staining
GridModel: Homemade / Material: COPPER / Mesh: 400 / Support film - Material: CARBON / Support film - topology: CONTINUOUS / Pretreatment - Type: GLOW DISCHARGE

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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
Sample stageSpecimen holder model: SIDE ENTRY, EUCENTRIC
Experimental equipment
Model: Tecnai Spirit / Image courtesy: FEI Company

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Image processing

CTF correctionType: NONE
Startup modelType of model: PDB ENTRY
PDB model - PDB ID:

6v0r


Details: coordinates converted map using UCSF Chimera molmap, and low pass filtered to 40 A
Final reconstructionApplied symmetry - Point group: C1 (asymmetric) / Resolution.type: BY AUTHOR / Resolution: 30.0 Å / Resolution method: FSC 0.5 CUT-OFF / Software - Name: RELION (ver. 3.1) / Number images used: 5786
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD

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