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- EMDB-70343: BG505 MD39.3-CC5 SOSIP in complex with V1V3 epitope polyclonal Fa... -

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Basic information

Entry
Database: EMDB / ID: EMD-70343
TitleBG505 MD39.3-CC5 SOSIP in complex with V1V3 epitope polyclonal Fabs isolated from HVTN302 human trial after dose 3 of mRNA-gp151-CD4KO immunization
Map datamain map
Sample
  • Complex: BG505 MD39.3-CC5 SOSIP in complex with V1V3 epitope polyclonal Fabs isolated from HVTN302 human trial after dose 3 of mRNA-gp151-CD4KO immunization
KeywordsHVTN 302 / clinical trial / HIV-1 / Env / vaccine-elicited / EMPEM / VIRAL PROTEIN
Biological speciesHuman immunodeficiency virus 1
Methodsingle particle reconstruction / negative staining / Resolution: 28.0 Å
AuthorsLee W-H / 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 Transl Med / Year: 2025
Title: Vaccination with mRNA-encoded membrane-anchored HIV envelope trimers elicited tier 2 neutralizing antibodies in a phase 1 clinical trial.
Authors: K Rachael Parks / Zoe Moodie / Mary A Allen / Catherine Yen / Briana D Furch / Kellie J MacPhee / Gabriel Ozorowski / Jack Heptinstall / William O Hahn / Zihan Zheng / Huiyin Lu / Shannon ...Authors: K Rachael Parks / Zoe Moodie / Mary A Allen / Catherine Yen / Briana D Furch / Kellie J MacPhee / Gabriel Ozorowski / Jack Heptinstall / William O Hahn / Zihan Zheng / Huiyin Lu / Shannon Grant / Elize Domin / Michael O Duff / Aaron Seese / Constanza Marini-Macouzet / Lamar Ballweber-Fleming / Wen-Hsin Lee / Christopher A Cottrell / Alessia Liguori / Erik Georgeson / Nushin Alavi / Michael Kubitz / Nicole Phelps / Kelly E Seaton / Kristen W Cohen / Maija A Anderson / Kajari Mondal / Dagna S Laufer / James G Kublin / Andrew B Ward / Ollivier Hyrien / Stephen C De Rosa / Sunny Himansu / Brett Leav / Caroline Reuter / Georgia D Tomaras / David Montefiori / Stephen R Walsh / Ian Frank / Magdalena E Sobieszczyk / Paul A Goepfert / Kathryn E Stephenson / Lindsey R Baden / Hong Van Tieu / Michael C Keefer / Jesse Clark / Sharon A Riddler / William R Schief / M Juliana McElrath /
Abstract: mRNA technology might accelerate development of an urgently needed preventive human immunodeficiency virus (HIV) vaccine. We evaluated the safety and immunogenicity of three mRNA-encoded envelope ...mRNA technology might accelerate development of an urgently needed preventive human immunodeficiency virus (HIV) vaccine. We evaluated the safety and immunogenicity of three mRNA-encoded envelope trimers, including two doses of soluble and membrane-anchored forms, in a randomized, open-label, phase 1 clinical trial. Vaccines were generally well tolerated, although 6.5% (7 of 108) of participants developed urticaria, a higher proportion than seen with other mRNA vaccines. mRNA-encoded trimers induced strong envelope-specific B and T cell responses. Immunization with membrane-anchored trimers, intended to obscure epitopes at the trimer base targeted by nonneutralizing antibodies, reduced the frequency of base-binding serum antibodies in comparison with soluble trimers. Three immunizations elicited autologous tier 2 serum neutralizing antibodies in 80% of vaccinees receiving the membrane-anchored trimers, in contrast to only 4% receiving the soluble trimer. Thus, with demonstration of more favorable safety, mRNA-encoded membrane-anchored HIV envelope trimers represent a promising platform for HIV vaccine clinical development.
History
DepositionApr 25, 2025-
Header (metadata) releaseAug 27, 2025-
Map releaseAug 27, 2025-
UpdateAug 27, 2025-
Current statusAug 27, 2025Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_70343.png

Downloads & links

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Map

FileDownload / File: emd_70343.map.gz / Format: CCP4 / Size: 3.4 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.)
3.78 Å/pix.
x 96 pix.
= 362.88 Å		3.78 Å/pix.
x 96 pix.
= 362.88 Å		3.78 Å/pix.
x 96 pix.
= 362.88 Å

Surface

Projections

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Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 3.78 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.02
Minimum - Maximum-0.050948802 - 0.098106615
Average (Standard dev.)0.00006224877 (±0.004744259)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions969696
Spacing969696
CellA=B=C: 362.88 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: half map B

Fileemd_70343_half_map_1.map
Annotationhalf map B
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 A

Fileemd_70343_half_map_2.map
Annotationhalf map A
Projections & Slices
AxesZYX

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Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Sample components

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Entire : BG505 MD39.3-CC5 SOSIP in complex with V1V3 epitope polyclonal Fa...

EntireName: BG505 MD39.3-CC5 SOSIP in complex with V1V3 epitope polyclonal Fabs isolated from HVTN302 human trial after dose 3 of mRNA-gp151-CD4KO immunization
Components
  • Complex: BG505 MD39.3-CC5 SOSIP in complex with V1V3 epitope polyclonal Fabs isolated from HVTN302 human trial after dose 3 of mRNA-gp151-CD4KO immunization

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Supramolecule #1: BG505 MD39.3-CC5 SOSIP in complex with V1V3 epitope polyclonal Fa...

SupramoleculeName: BG505 MD39.3-CC5 SOSIP in complex with V1V3 epitope polyclonal Fabs isolated from HVTN302 human trial after dose 3 of mRNA-gp151-CD4KO immunization
type: complex / ID: 1 / Parent: 0
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
GridModel: Homemade / Material: COPPER / Mesh: 400 / Support film - Material: CARBON / Support film - topology: CONTINUOUS

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Electron microscopy

MicroscopeTFS GLACIOS
Image recordingFilm or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 16.0 e/Å2
Electron beamAcceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 1.0 µm
Sample stageSpecimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER

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Image processing

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

6v0r


Details: coordinates converted to map using UCSF Chimera molmap and low pass filtered to 40 A
Final reconstructionResolution.type: BY AUTHOR / Resolution: 28.0 Å / Resolution method: FSC 0.5 CUT-OFF / Software - Name: RELION / Number images used: 4700
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD

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