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- EMDB-27706: Vaccine elicited Antibody MU89 bound to CH848.D949.10.17_N133D_N1... -

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Entry
Database: EMDB / ID: EMD-27706
TitleVaccine elicited Antibody MU89 bound to CH848.D949.10.17_N133D_N138T.DS.SOSIP.664 HIV-1 Env trimer
Map dataZ-Sharpened map from homogeneous C3 refinement in cryosparc (Sharpened in Phenix)
Sample
  • Complex: V3-glycan vaccine induced antibody MU89 in complex with CH848.3.D0949.10.17chim.6R.DS.SOSIP.664_N133D_N138T HIV Env trimer
    • Protein or peptide: CH848.3.D0949.10.17chim.6R.DS.SOSIP.664_N133D_N138T gp120
    • Protein or peptide: Envelope Glycoprotein gp141
    • Protein or peptide: MU89 Heavy Chain
    • Protein or peptide: MU89 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 speciesHomo sapiens (human) / Human immunodeficiency virus 1 / Human immunodeficiency virus / Mus musculus (house mouse)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.57 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 / Weissman D / Alt FW / Acharya P / Haynes BF
History
DepositionJul 26, 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_27706.png

Downloads & links

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Map

FileDownload / File: emd_27706.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationZ-Sharpened map from homogeneous C3 refinement in cryosparc (Sharpened in Phenix)
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: 1.35
Minimum - Maximum-1.37662 - 4.7748747
Average (Standard dev.)0.0014955527 (±0.14627986)
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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Mask #1

Fileemd_27706_msk_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
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Histogram

Histogram (log scale)

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Additional map: Sharp map from homogeneous C3 refinement in cryosparc

Fileemd_27706_additional_1.map
AnnotationSharp 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 A map from homogeneous C3 refinement in cryosparc

Fileemd_27706_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_27706_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 in complex with CH848.3.D...

EntireName: V3-glycan vaccine induced antibody MU89 in complex with CH848.3.D0949.10.17chim.6R.DS.SOSIP.664_N133D_N138T HIV Env trimer
Components
  • Complex: V3-glycan vaccine induced antibody MU89 in complex with CH848.3.D0949.10.17chim.6R.DS.SOSIP.664_N133D_N138T HIV Env trimer
    • Protein or peptide: CH848.3.D0949.10.17chim.6R.DS.SOSIP.664_N133D_N138T gp120
    • Protein or peptide: Envelope Glycoprotein gp141
    • Protein or peptide: MU89 Heavy Chain
    • Protein or peptide: MU89 Light Chain
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose

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Supramolecule #1: V3-glycan vaccine induced antibody MU89 in complex with CH848.3.D...

SupramoleculeName: V3-glycan vaccine induced antibody MU89 in complex with CH848.3.D0949.10.17chim.6R.DS.SOSIP.664_N133D_N138T HIV Env trimer
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#4
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 360 KDa

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Macromolecule #1: CH848.3.D0949.10.17chim.6R.DS.SOSIP.664_N133D_N138T gp120

MacromoleculeName: CH848.3.D0949.10.17chim.6R.DS.SOSIP.664_N133D_N138T gp120
type: protein_or_peptide / ID: 1
Details: CH848.3.D0949.10.17chim.6R.DS.SOSIP.664_N133D_N138T
Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Human immunodeficiency virus 1
Molecular weightTheoretical: 54.136465 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 VVG

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Macromolecule #2: Envelope Glycoprotein gp141

MacromoleculeName: Envelope Glycoprotein gp141 / type: protein_or_peptide / ID: 2
Details: CH848.3.D0949.10.17chim.6R.DS.SOSIP.664_N133D_N138T
Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Human immunodeficiency virus
Molecular weightTheoretical: 17.146482 KDa
Recombinant expressionOrganism: Mammalia (mammals)
SequenceString:
AVGIGAVFLG FLGAAGSTMG AASMTLTVQA RNLLSGIVQQ QSNLLRAPEA QQHLLKLTVW GIKQLQARVL AVERYLRDQQ LLGIWGCSG KLICCTNVPW NSSWSNRNLS EIWDNMTWLQ WDKEISNYTQ IIYGLLEESQ NQQEKNEQDL LALD

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Macromolecule #3: MU89 Heavy Chain

MacromoleculeName: MU89 Heavy Chain / type: protein_or_peptide / ID: 3 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Mus musculus (house mouse)
Molecular weightTheoretical: 14.17273 KDa
Recombinant expressionOrganism: Mammalia (mammals)
SequenceString:
QVQLVQSGAE VKKPGASVKV SCKASGYRFT DHYIHWVRQA PGQGPEWMGW INTSSGRSNF AQKFQGRVTM TRDTSISTAY MELNRLKSD DTAVYYCTTG SWISLYYDSS GYPNFDYWGQ GTLVTVT

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Macromolecule #4: MU89 Light Chain

MacromoleculeName: MU89 Light Chain / type: protein_or_peptide / ID: 4 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Mus musculus (house mouse)
Molecular weightTheoretical: 10.989062 KDa
Recombinant expressionOrganism: Mammalia (mammals)
SequenceString:
TQPASVSGSP GQPITISCTG TSSDVGNYDL VSWYQQHPGN APKYMIYEVT KRPAGISNRF SGSKSGNTAS LTISGLQAED AADYYCCSY AGSSTVIFGG GTKVTVL

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Macromolecule #11: 2-acetamido-2-deoxy-beta-D-glucopyranose

MacromoleculeName: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 11 / Number of copies: 12 / 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 real images: 1787 / Average electron dose: 58.9 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: 990218
Startup modelType of model: NONE
Final reconstructionAlgorithm: FOURIER SPACE / Resolution.type: BY AUTHOR / Resolution: 3.57 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC (ver. 3.2) / Number images used: 72478
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 modelPDB ID:

6um6


Chain - Source name: PDB / Chain - Initial model type: experimental model
RefinementSpace: REAL / Protocol: FLEXIBLE FIT
Output model

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

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