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- EMDB-27776: Vaccine elicited Antibody MU89+S27Y bound to CH848.D949.10.17_N13... -

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Basic information

Entry
Database: EMDB / ID: EMD-27776
TitleVaccine elicited Antibody MU89+S27Y bound to CH848.D949.10.17_N133D_N138T.DS.SOSIP.664 HIV-1 Env trimer
Map dataSharpened map from homogeneous C3 refinement in cryosparc
Sample
  • Complex: V3-glycan vaccine induced antibody MU89+S27Y in complex with CH848.D949.10.17_N133D_N138T.DS.SOSIP.664 HIV Env trimer
    • Protein or peptide: Envelope glycoprotein gp160
    • Protein or peptide: MU89+S27Y Heavy Chain
    • Protein or peptide: MU89+S27Y Light Chain
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
KeywordsHIV-1 envelope / vaccine-induced antibody / broadly neutralizing antibody / VIRAL PROTEIN-IMMUNE SYSTEM complex
Biological speciesHuman immunodeficiency virus 1 / Mus musculus (house mouse)
Methodsingle particle reconstruction / cryo EM / Resolution: 4.32 Å
AuthorsStalls V / Acharya P
Funding support United States, 1 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)UM1-AI144371 United States
Citation
Journal: Cell Host Microbe / Year: 2024
Title: Mutation-guided vaccine design: A process for developing boosting immunogens for HIV broadly neutralizing antibody induction.
Authors: Kevin Wiehe / Kevin O Saunders / Victoria Stalls / Derek W Cain / Sravani Venkatayogi / Joshua S Martin Beem / Madison Berry / Tyler Evangelous / Rory Henderson / Bhavna Hora / Shi-Mao Xia / ...Authors: Kevin Wiehe / Kevin O Saunders / Victoria Stalls / Derek W Cain / Sravani Venkatayogi / Joshua S Martin Beem / Madison Berry / Tyler Evangelous / Rory Henderson / Bhavna Hora / Shi-Mao Xia / Chuancang Jiang / Amanda Newman / Cindy Bowman / Xiaozhi Lu / Mary E Bryan / Joena Bal / Aja Sanzone / Haiyan Chen / Amanda Eaton / Mark A Tomai / Christopher B Fox / Ying K Tam / Christopher Barbosa / Mattia Bonsignori / Hiromi Muramatsu / S Munir Alam / David C Montefiori / Wilton B Williams / Norbert Pardi / Ming Tian / Drew Weissman / Frederick W Alt / Priyamvada Acharya / Barton F Haynes /
Abstract: A major goal of HIV-1 vaccine development is the induction of broadly neutralizing antibodies (bnAbs). Although success has been achieved in initiating bnAb B cell lineages, design of boosting ...A major goal of HIV-1 vaccine development is the induction of broadly neutralizing antibodies (bnAbs). Although success has been achieved in initiating bnAb B cell lineages, design of boosting immunogens that select for bnAb B cell receptors with improbable mutations required for bnAb affinity maturation remains difficult. Here, we demonstrate a process for designing boosting immunogens for a V3-glycan bnAb B cell lineage. The immunogens induced affinity-matured antibodies by selecting for functional improbable mutations in bnAb precursor knockin mice. Moreover, we show similar success in prime and boosting with nucleoside-modified mRNA-encoded HIV-1 envelope trimer immunogens, with improved selection by mRNA immunogens of improbable mutations required for bnAb binding to key envelope glycans. These results demonstrate the ability of both protein and mRNA prime-boost immunogens for selection of rare B cell lineage intermediates with neutralizing breadth after bnAb precursor expansion, a key proof of concept and milestone toward development of an HIV-1 vaccine.
#1: Journal: bioRxiv / Year: 2022
Title: Mutation-Guided Vaccine Design: A Strategy for Developing Boosting Immunogens for HIV Broadly Neutralizing Antibody Induction
Authors: Wiehe K / Saunders KO / Stalls V / Cain D / Venkatayogi S / Martin Beem JS / Berry M / Evangelous T / Henderson R / Hora B / Xia S / Jiang C / Newman A / Bowman C / Lu X / Bryan ME / Bal J / ...Authors: Wiehe K / Saunders KO / Stalls V / Cain D / Venkatayogi S / Martin Beem JS / Berry M / Evangelous T / Henderson R / Hora B / Xia S / Jiang C / Newman A / Bowman C / Lu X / Bryan ME / Bal J / Sanzone A / Chen H / Eaton A / Tomai MA / Fox CB / Tam Y / Barbosa C / Bonsignori M / Muramatsu H / Alam SM / Montefiori D / Williams WB / Pardi N / Tian M / Weisman D / Alt FW / Acharya P / Haynes BF
History
DepositionAug 3, 2022-
Header (metadata) releaseApr 19, 2023-
Map releaseApr 19, 2023-
UpdateOct 16, 2024-
Current statusOct 16, 2024Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_27776.png

Downloads & links

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Map

FileDownload / File: emd_27776.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationSharpened map from homogeneous C3 refinement in cryosparc
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.08 Å/pix.
x 320 pix.
= 345.6 Å		1.08 Å/pix.
x 320 pix.
= 345.6 Å		1.08 Å/pix.
x 320 pix.
= 345.6 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.08 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 1.05
Minimum - Maximum-0.43932295 - 2.7434394
Average (Standard dev.)0.006073775 (±0.12829138)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions320320320
Spacing320320320
CellA=B=C: 345.6 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: Half A map from homogeneous C3 refinement in cryosparc

Fileemd_27776_half_map_1.map
AnnotationHalf A map from homogeneous C3 refinement in cryosparc
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: Half B map from homogeneous C3 refinement in cryosparc

Fileemd_27776_half_map_2.map
AnnotationHalf B map from homogeneous C3 refinement in cryosparc
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Sample components

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Entire : V3-glycan vaccine induced antibody MU89+S27Y in complex with CH84...

EntireName: V3-glycan vaccine induced antibody MU89+S27Y in complex with CH848.D949.10.17_N133D_N138T.DS.SOSIP.664 HIV Env trimer
Components
  • Complex: V3-glycan vaccine induced antibody MU89+S27Y in complex with CH848.D949.10.17_N133D_N138T.DS.SOSIP.664 HIV Env trimer
    • Protein or peptide: Envelope glycoprotein gp160
    • Protein or peptide: MU89+S27Y Heavy Chain
    • Protein or peptide: MU89+S27Y Light Chain
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose

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Supramolecule #1: V3-glycan vaccine induced antibody MU89+S27Y in complex with CH84...

SupramoleculeName: V3-glycan vaccine induced antibody MU89+S27Y in complex with CH848.D949.10.17_N133D_N138T.DS.SOSIP.664 HIV Env trimer
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3
Source (natural)Organism: Human immunodeficiency virus 1
Molecular weightTheoretical: 360 KDa

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Macromolecule #1: Envelope glycoprotein gp160

MacromoleculeName: Envelope glycoprotein gp160 / type: protein_or_peptide / ID: 1 / Details: CH848.D949.10.17_N133D_N138T.DS.SOSIP.664 HIV-1 / Number of copies: 6 / Enantiomer: LEVO
Source (natural)Organism: Human immunodeficiency virus 1
Molecular weightTheoretical: 72.208086 KDa
Recombinant expressionOrganism: Mammalia (mammals)
SequenceString: MGSLQPLATL YLLGMLVASV LAAENLWVTV YYGVPVWKEA KTTLFCASDA RAYEKEVHNV WATHACVPTD PSPQELVLGN VTENFNMWK NDMVDQMHED IISLWDQSLK PCVKLTPLCV TLICSDATVK TGTVEEMKNC SFNTTTEIRD KEKKEYALFY K PDIVPLSE ...String:
MGSLQPLATL YLLGMLVASV LAAENLWVTV YYGVPVWKEA KTTLFCASDA RAYEKEVHNV WATHACVPTD PSPQELVLGN VTENFNMWK NDMVDQMHED IISLWDQSLK PCVKLTPLCV TLICSDATVK TGTVEEMKNC SFNTTTEIRD KEKKEYALFY K PDIVPLSE TNNTSEYRLI NCNTSACTQA CPKVTFEPIP IHYCAPAGYA ILKCNDETFN GTGPCSNVST VQCTHGIRPV VS TQLLLNG SLAEKEIVIR SENLTNNAKI IIVHLHTPVE IVCTRPNNNT RKSVRIGPGQ TFYATGDIIG DIKQAHCNIS EEK WNDTLQ KVGIELQKHF PNKTIKYNQS AGGDMEITTH SFNCGGEFFY CNTSNLFNGT YNGTYISTNS SANSTSTITL QCRI KQIIN MWQGVGRCMY APPIAGNITC RSNITGLLLT RDGGTNSNET ETFRPAGGDM RDNWRSELYK YKVVKIEPLG VAPTR CKRR VVGRRRRRRA VGIGAVFLGF LGAAGSTMGA ASMTLTVQAR NLLSGIVQQQ SNLLRAPEAQ QHLLKLTVWG IKQLQA RVL AVERYLRDQQ LLGIWGCSGK LICCTNVPWN SSWSNRNLSE IWDNMTWLQW DKEISNYTQI IYGLLEESQN QQEKNEQ DL LALD

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Macromolecule #2: MU89+S27Y Heavy Chain

MacromoleculeName: MU89+S27Y Heavy Chain / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Mus musculus (house mouse)
Molecular weightTheoretical: 16.162116 KDa
Recombinant expressionOrganism: Mammalia (mammals)
SequenceString:
MGWSCIILFL VATATGVHSQ VQLVQSGAEV KKPGASVKVS CKASGYRFTD HYIHWVRQAP GQGPEWMGWI NTSSGRSNFA QKFQGRVTM TRDTSISTAY MELNRLKSDD TAVYYCTTGS WISLYYDSSG YPNFDYWGQG TLVTVT

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Macromolecule #3: MU89+S27Y Light Chain

MacromoleculeName: MU89+S27Y Light Chain / type: protein_or_peptide / ID: 3 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Mus musculus (house mouse)
Molecular weightTheoretical: 11.464601 KDa
Recombinant expressionOrganism: Mammalia (mammals)
SequenceString:
QSALTQPASV SGSPGQPITI SCTGTSYDVG NYDLVSWYQQ HPGNAPKYMI YEVTKRPAGI SNRFSGSKSG NTASLTISGL QAEDAADYY CCSYAGSSTV IFGGGTKVTV L

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Macromolecule #10: 2-acetamido-2-deoxy-beta-D-glucopyranose

MacromoleculeName: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 10 / Number of copies: 9 / Formula: NAG
Molecular weightTheoretical: 221.208 Da
Chemical component information

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

Concentration1.5 mg/mL
BufferpH: 7.4
GridModel: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 300 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE
VitrificationCryogen name: ETHANE / Chamber humidity: 90 % / Instrument: LEICA EM GP

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Number grids imaged: 1 / Number real images: 1801 / Average electron dose: 59.3 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 2.5 µm / Nominal defocus min: 0.7000000000000001 µm
Sample stageCooling holder cryogen: NITROGEN
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Particle selectionNumber selected: 1002697
Startup modelType of model: NONE
Final reconstructionAlgorithm: FOURIER SPACE / Resolution.type: BY AUTHOR / Resolution: 4.32 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC (ver. 3.2) / Number images used: 65441
Initial angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC (ver. 3.2)
Final angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC (ver. 3.2)
Final 3D classificationSoftware - Name: cryoSPARC (ver. 3.2)

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Atomic model buiding 1

Initial model
PDB IDChain

6um6

source_name: PDB, initial_model_type: experimental model

8dto

source_name: PDB, initial_model_type: experimental model
RefinementSpace: REAL / Protocol: FLEXIBLE FIT
Output model

PDB-8dy6:
Vaccine elicited Antibody MU89+S27Y bound to CH848.D949.10.17_N133D_N138T.DS.SOSIP.664 HIV-1 Env trimer

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