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- EMDB-40815: BG505 SOSIP.664 in complex with wk26 human polyclonal antibodies ... -

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Basic information

Entry
Database: EMDB / ID: EMD-40815
TitleBG505 SOSIP.664 in complex with wk26 human polyclonal antibodies C3V5, V1V3, N611 and base from participant 017
Map datamap with C3V5 antibody
Sample
  • Complex: BG505 SOSIP.664 in complex with wk26 human polyclonal antibodies C3V5, V1V3, N611 and base from participant 017
Keywordshuman clinical trial / hiv vaccine / Env / polyclonal antibodies / EMPEM / VIRAL PROTEIN
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / negative staining / Resolution: 23.0 Å
AuthorsKarlinsey D / Ozorowski G / Ward AB
Funding support United States, 1 items
OrganizationGrant numberCountry
Bill & Melinda Gates FoundationINV-002916 United States
CitationJournal: medRxiv / Year: 2024
Title: HIV BG505 SOSIP.664 trimer with 3M-052-AF/alum induces human autologous tier-2 neutralizing antibodies.
Abstract: Stabilized trimers preserving the native-like HIV envelope structure may be key components of a preventive HIV vaccine regimen to induce broadly neutralizing antibodies (bnAbs). We evaluated trimeric ...Stabilized trimers preserving the native-like HIV envelope structure may be key components of a preventive HIV vaccine regimen to induce broadly neutralizing antibodies (bnAbs). We evaluated trimeric BG505 SOSIP.664 gp140, formulated with a novel TLR7/8 signaling adjuvant, 3M-052-AF/Alum, for safety, adjuvant dose-finding and immunogenicity in a first-in-healthy adult (n=17), randomized, placebo-controlled trial (HVTN 137A). The vaccine regimen appeared safe. Robust, trimer-specific antibody, B-cell and CD4+ T-cell responses emerged post-vaccination. Five vaccinees developed serum autologous tier-2 nAbs (ID50 titer, 1:28-1:8647) after 2-3 doses targeting C3/V5 and/or V1/V2/V3 Env regions by electron microscopy and mutated pseudovirus-based neutralization analyses. Trimer-specific, B-cell-derived monoclonal antibody activities confirmed these results and showed weak heterologous neutralization in the strongest responder. Our findings demonstrate the clinical utility of the 3M-052-AF/alum adjuvant and support further improvements of trimer-based Env immunogens to focus responses on multiple broad nAb epitopes.
KEY TAKEAWAY/TAKE-HOME MESSAGES: HIV BG505 SOSIP.664 trimer with novel 3M-052-AF/alum adjuvant in humans appears safe and induces serum neutralizing antibodies to matched clade A, tier 2 virus, that ...KEY TAKEAWAY/TAKE-HOME MESSAGES: HIV BG505 SOSIP.664 trimer with novel 3M-052-AF/alum adjuvant in humans appears safe and induces serum neutralizing antibodies to matched clade A, tier 2 virus, that map to diverse Env epitopes with relatively high titers. The novel adjuvant may be an important mediator of vaccine response.
History
DepositionMay 18, 2023-
Header (metadata) releaseMay 22, 2024-
Map releaseMay 22, 2024-
UpdateJun 5, 2024-
Current statusJun 5, 2024Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_40815.png

Downloads & links

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Map

FileDownload / File: emd_40815.map.gz / Format: CCP4 / Size: 42.9 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Annotationmap with C3V5 antibody
Projections & slices

Image control

Size
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AxesZ (Sec.)Y (Row.)X (Col.)
1.67 Å/pix.
x 224 pix.
= 373.408 Å		1.67 Å/pix.
x 224 pix.
= 373.408 Å		1.67 Å/pix.
x 224 pix.
= 373.408 Å

Surface

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Images are generated by Spider.

Voxel sizeX=Y=Z: 1.667 Å
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Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.01
Minimum - Maximum-0.029962147 - 0.07289013
Average (Standard dev.)-0.00006112917 (±0.0026434688)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions224224224
Spacing224224224
CellA=B=C: 373.40802 Å
α=β=γ: 90.0 °

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Supplemental data

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Additional map: additional map 1 with N611 antibody

Fileemd_40815_additional_1.map
Annotationadditional map 1 with N611 antibody
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Additional map: additional map 2 with base antibody

Fileemd_40815_additional_2.map
Annotationadditional map 2 with base antibody
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Additional map: additional map 3 with V1V3 antibody

Fileemd_40815_additional_3.map
Annotationadditional map 3 with V1V3 antibody
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Half map: #1

Fileemd_40815_half_map_1.map
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Half map: half map 1

Fileemd_40815_half_map_2.map
Annotationhalf map 1
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Sample components

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Entire : BG505 SOSIP.664 in complex with wk26 human polyclonal antibodies ...

EntireName: BG505 SOSIP.664 in complex with wk26 human polyclonal antibodies C3V5, V1V3, N611 and base from participant 017
Components
  • Complex: BG505 SOSIP.664 in complex with wk26 human polyclonal antibodies C3V5, V1V3, N611 and base from participant 017

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Supramolecule #1: BG505 SOSIP.664 in complex with wk26 human polyclonal antibodies ...

SupramoleculeName: BG505 SOSIP.664 in complex with wk26 human polyclonal antibodies C3V5, V1V3, N611 and base from participant 017
type: complex / ID: 1 / Parent: 0
Details: Polyclonal antibodies isolated from human serum and digested to Fab using papain
Source (natural)Organism: Homo sapiens (human)

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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
Component:
ConcentrationName
50.0 mMTris
150.0 mMsodium chloride
StainingType: NEGATIVE / Material: uranyl formate
GridModel: Homemade / Material: COPPER / Mesh: 400 / Support film - Material: PARLODION / Support film - topology: CONTINUOUS / Pretreatment - Type: GLOW DISCHARGE

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Electron microscopy

MicroscopeFEI TECNAI F20
Electron beamAcceleration voltage: 120 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 / Nominal magnification: 73000
Sample stageSpecimen holder model: SIDE ENTRY, EUCENTRIC
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

Startup modelType of model: PDB ENTRY
PDB model - PDB ID:

4zmj


Details: Map created from atomic coordinates using Molmap function in UCSF Chimera
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
Final reconstructionApplied symmetry - Point group: C1 (asymmetric) / Resolution.type: BY AUTHOR / Resolution: 23.0 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: RELION (ver. 3.0) / Number images used: 11380

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