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- EMDB-48591: G002-480-0546 Fab in complex with V703-0537_T278M_L14 SOSIP and B... -

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Entry
Database: EMDB / ID: EMD-48591
TitleG002-480-0546 Fab in complex with V703-0537_T278M_L14 SOSIP and BG18 Fab
Map datasharpened map
Sample
  • Complex: G002-480-0546 Fab in complex with V703-0537_T278M_L14 SOSIP and BG18 Fab
    • Protein or peptide: V703-0537_T278M_L14 SOSIP
    • Protein or peptide: BG18 Fab heavy chain
    • Protein or peptide: BG18 Fab light chain
    • Protein or peptide: G002-480-0546 Fab light chain
    • Protein or peptide: G002-480-0546 Fab heavy chain
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
KeywordsG002 / clinical trial / HIV-1 / VRC01 / human antibody / vaccine / Env / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex
Biological speciesHuman immunodeficiency virus 1 / Homo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.4 Å
AuthorsPhulera S / Ozorowski G / Ward AB
Funding support United States, 1 items
OrganizationGrant numberCountry
Bill & Melinda Gates FoundationINV-002916 United States
CitationJournal: Science / Year: 2025
Title: Vaccination with mRNA-encoded nanoparticles drives early maturation of HIV bnAb precursors in humans.
Authors: Jordan R Willis / Madhu Prabhakaran / Michelle Muthui / Ansuya Naidoo / Troy Sincomb / Weiwei Wu / Christopher A Cottrell / Elise Landais / Allan C deCamp / Nahid R Keshavarzi / Oleksandr ...Authors: Jordan R Willis / Madhu Prabhakaran / Michelle Muthui / Ansuya Naidoo / Troy Sincomb / Weiwei Wu / Christopher A Cottrell / Elise Landais / Allan C deCamp / Nahid R Keshavarzi / Oleksandr Kalyuzhniy / Jeong Hyun Lee / Linda M Murungi / Wilfrida A Ogonda / Nicole L Yates / Martin M Corcoran / Swastik Phulera / Joel Musando / Amanda Tsai / Gabrielle Lemire / Yiakon Sein / Michael Muteti / Praveen Alamuri / Jennifer A Bohl / Drienna Holman / Sunny Himansu / Brett Leav / Caroline Reuter / Li-An Lin / Baoyu Ding / Chunla He / Walter L Straus / Kellie J MacPhee / Isabel Regadas / Diana V Nyabundi / Ruth Chirchir / Aggrey Anzala / John N Kimotho / Caleb Kibet / Kelli Greene / Hongmei Gao / Erica Beatman / Kiara Benson / Dominick Laddy / David M Brown / Rhianna Bronson / Jalen Baptiste / Suprabhath Gajjala / Zahra Rikhtegaran-Tehrani / Alison Benner / Mukundhan Ramaswami / Danny Lu / Nushin Alavi / Sonya Amirzehni / Michael Kubitz / Ryan Tingle / Erik Georgeson / Nicole Phelps / Yumiko Adachi / Alessia Liguori / Claudia Flynn / Katherine McKenney / Xiaoya Zhou / D Collins Owuor / Sharon Owuor / Soo-Young Kim / Michael Duff / Ju Yeong Kim / Grace Gibson / Sabyasachi Baboo / Jolene Diedrich / Torben Schiffner / Marisa Shields / Mabela Matsoso / Jennifer Santos / Kristen Syvertsen / Allison Kennedy / Melissa Schroeter / Johan Vekemans / John Yates / James C Paulson / Ollivier Hyrien / Adrian B McDermott / Pholo Maenetje / Julien Nyombayire / Etienne Karita / Rosine Ingabire / Vinodh Edward / Vincent Muturi-Kioi / Janine Maenza / Adrienne E Shapiro / M Juliana McElrath / Srilatha Edupuganti / Barbara S Taylor / David Diemert / Gabriel Ozorowski / Richard A Koup / David Montefiori / Andrew B Ward / Gunilla Karlsson Hedestam / Georgia Tomaras / Devin J Hunt / Daniel Muema / Devin Sok / Dagna S Laufer / Sarah F Andrews / Eunice W Nduati / William R Schief /
Abstract: A leading HIV vaccine strategy requires a priming immunogen to induce broadly neutralizing antibody (bnAb) precursors, followed by a series of heterologous boosters to elicit somatic hypermutation ...A leading HIV vaccine strategy requires a priming immunogen to induce broadly neutralizing antibody (bnAb) precursors, followed by a series of heterologous boosters to elicit somatic hypermutation (SHM) and produce bnAbs. In two randomized, open-label phase 1 human clinical trials, IAVI-G002 in the United States and IAVI-G003 in Rwanda and South Africa, we evaluated the safety and immunogenicity of mRNA-encoded nanoparticles as priming immunogens (both trials) and first-boosting immunogens (IAVI-G002). The vaccines were generally safe and well tolerated, except 18% of IAVI-G002 participants experienced skin reactions. Priming induced bnAb precursors with substantial frequencies and SHM, and heterologous boosting elicited increased SHM, affinity, and neutralization activity toward bnAb development. The results establish clinical proof of concept that heterologous boosting can advance bnAb-precursor maturation and demonstrate bnAb priming in Africa where the HIV burden is highest.
History
DepositionJan 10, 2025-
Header (metadata) releaseMay 28, 2025-
Map releaseMay 28, 2025-
UpdateMay 28, 2025-
Current statusMay 28, 2025Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_48591.png

Downloads & links

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Map

FileDownload / File: emd_48591.map.gz / Format: CCP4 / Size: 244.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Annotationsharpened map
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.03 Å/pix.
x 400 pix.
= 413.56 Å		1.03 Å/pix.
x 400 pix.
= 413.56 Å		1.03 Å/pix.
x 400 pix.
= 413.56 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.0339 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.12
Minimum - Maximum-0.5874584 - 1.0536613
Average (Standard dev.)-0.00021797263 (±0.018699834)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions400400400
Spacing400400400
CellA=B=C: 413.56 Å
α=β=γ: 90.0 °

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Supplemental data

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Mask #1

Fileemd_48591_msk_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: half map B

Fileemd_48591_half_map_1.map
Annotationhalf map B
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: half map B

Fileemd_48591_half_map_2.map
Annotationhalf map B
Projections & Slices
AxesZYX

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Histogram

Histogram (log scale)

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Sample components

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Entire : G002-480-0546 Fab in complex with V703-0537_T278M_L14 SOSIP and B...

EntireName: G002-480-0546 Fab in complex with V703-0537_T278M_L14 SOSIP and BG18 Fab
Components
  • Complex: G002-480-0546 Fab in complex with V703-0537_T278M_L14 SOSIP and BG18 Fab
    • Protein or peptide: V703-0537_T278M_L14 SOSIP
    • Protein or peptide: BG18 Fab heavy chain
    • Protein or peptide: BG18 Fab light chain
    • Protein or peptide: G002-480-0546 Fab light chain
    • Protein or peptide: G002-480-0546 Fab heavy chain
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose

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Supramolecule #1: G002-480-0546 Fab in complex with V703-0537_T278M_L14 SOSIP and B...

SupramoleculeName: G002-480-0546 Fab in complex with V703-0537_T278M_L14 SOSIP and BG18 Fab
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#5

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Macromolecule #1: V703-0537_T278M_L14 SOSIP

MacromoleculeName: V703-0537_T278M_L14 SOSIP / type: protein_or_peptide / ID: 1
Details: Envelope glycoprotein gp160 with V703-0537_T278M_L14 SOSIP engineered mutations
Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Human immunodeficiency virus 1
Molecular weightTheoretical: 72.756375 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: ETGAEDLWVT VYYGVPVWRD AITTLFCASD AKAYEKEVHN VWATHACVPT DPNPQEMVLE NVTENFNMWK NNMVDQMHED IISLWDQSL KPCVQLTPLC VTLNCTDVVG NNTATRRNNT ATRRNNTATI NDTDTGIKNC SFNITTEVRD KKKKVHALFY R LDIVPIDG ...String:
ETGAEDLWVT VYYGVPVWRD AITTLFCASD AKAYEKEVHN VWATHACVPT DPNPQEMVLE NVTENFNMWK NNMVDQMHED IISLWDQSL KPCVQLTPLC VTLNCTDVVG NNTATRRNNT ATRRNNTATI NDTDTGIKNC SFNITTEVRD KKKKVHALFY R LDIVPIDG KNSNSTEYIL INCNTSVITQ ICPKVSFDPI PIHYCAPAGY AILKCNNKTF NGTGPCNNVS TIQCTHGIKP VV STQLLLN GSLAEEDIII SSENMMDNTK TIIVHFNESV GIECTRPNNN TVESIRIGPG QTFYVTGEII GDIRQAHCNI SKG NWSKTL QRVKEKLKKY YHNKTIKFEP SSGGDLEITT HSFNCRGEFF YCYTSGLFNE SIVNGTNGTI TLPCRIKQIV NMWQ KVGRA MYAPPIAGNI TCSSNITGLL LTRDGGRGTN GTETFRPAGG NMKDNWRSEL YKYKVVEIKP LGIAPTKCRR RVVGS HSGS GGSGSGGHAA VLGTAILGFL GAAGSTMGAA SNALFVQTRQ LLSGFVQQQS NLPKAPKAQQ QLLQLGVWGI KQLQTR VLA IERYLEVQQF LGLWGCSGKA ICCTAVPWNT TWSNKSEQEI WNNMTWMQWD REVGNYTDTI YKLLFVAQFQ QEINEVD LL ALNGTKHHHH HH

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Macromolecule #2: BG18 Fab heavy chain

MacromoleculeName: BG18 Fab heavy chain / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 25.043186 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: QVQLRESGPG LVKPSETLSL SCTVSNDSRP SDHSWTWVRQ SPGKALEWIG DIHYNGATTY NPSLRSRVRI ELDQSIPRFS LKMTSMTAA DTGMYYCARN AIRIYGVVAL GEWFHYGMDV WGQGTAVTVS SASTKGPSVF PLAPSSKSTS GGTAALGCLV K DYFPEPVT ...String:
QVQLRESGPG LVKPSETLSL SCTVSNDSRP SDHSWTWVRQ SPGKALEWIG DIHYNGATTY NPSLRSRVRI ELDQSIPRFS LKMTSMTAA DTGMYYCARN AIRIYGVVAL GEWFHYGMDV WGQGTAVTVS SASTKGPSVF PLAPSSKSTS GGTAALGCLV K DYFPEPVT VSWNSGALTS GVHTFPAVLQ SSGLYSLSSV VTVPSSSLGT QTYICNVNHK PSNTKVDKKV EPKSC

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Macromolecule #3: BG18 Fab light chain

MacromoleculeName: BG18 Fab light chain / type: protein_or_peptide / ID: 3 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 22.937352 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: SSELTQPPSV SVSPGQTARI TCSGAPLTSR FTYWYRQKPG QAPVLIISRS SQRSSGWSGR FSASWSGTTV TLTIRGVQAD DEADYYCQS SDTSDSYKMF GGGTKLTVLG QPKAAPSVTL FPPSSEELQA NKATLVCLIS DFYPGAVTVA WKADSSPVKA G VETTTPSK ...String:
SSELTQPPSV SVSPGQTARI TCSGAPLTSR FTYWYRQKPG QAPVLIISRS SQRSSGWSGR FSASWSGTTV TLTIRGVQAD DEADYYCQS SDTSDSYKMF GGGTKLTVLG QPKAAPSVTL FPPSSEELQA NKATLVCLIS DFYPGAVTVA WKADSSPVKA G VETTTPSK QSNNKYAASS YLSLTPEQWK SHRSYSCQVT HEGSTVEKTV APTECS

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Macromolecule #4: G002-480-0546 Fab light chain

MacromoleculeName: G002-480-0546 Fab light chain / type: protein_or_peptide / ID: 4 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 22.95749 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: EIVLTQSPGT LSLSPGEGAT LSCRTSQSLS SSSLAWYQQK PGLAPRLLIY GASIRATGIP DRFSGSGSGT DFTLTISRLE PEDFAVYYC QQYEFFGAGT RVEIKRTVAA PSVFIFPPSD EQLKSGTASV VCLLNNFYPR EAKVQWKVDN ALQSGNSQES V TEQDSKDS ...String:
EIVLTQSPGT LSLSPGEGAT LSCRTSQSLS SSSLAWYQQK PGLAPRLLIY GASIRATGIP DRFSGSGSGT DFTLTISRLE PEDFAVYYC QQYEFFGAGT RVEIKRTVAA PSVFIFPPSD EQLKSGTASV VCLLNNFYPR EAKVQWKVDN ALQSGNSQES V TEQDSKDS TYSLSSTLTL SKADYEKHKV YACEVTHQGL SSPVTKSFNR GEC

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Macromolecule #5: G002-480-0546 Fab heavy chain

MacromoleculeName: G002-480-0546 Fab heavy chain / type: protein_or_peptide / ID: 5 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 24.541561 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: QVQLVQSGAE LKKPGASVKV SCKASGYTFT DSYMHWVRQA PGQGLEWMGW INPNYGATNY AHKFQGRVTM TRDTSITTAY MELNRLRSD DTAVYYCARG NFLRVDYTWD FQHWGQGTLV TVSSASTKGP SVFPLAPSSK STSGGTAALG CLVKDYFPEP V TVSWNSGA ...String:
QVQLVQSGAE LKKPGASVKV SCKASGYTFT DSYMHWVRQA PGQGLEWMGW INPNYGATNY AHKFQGRVTM TRDTSITTAY MELNRLRSD DTAVYYCARG NFLRVDYTWD FQHWGQGTLV TVSSASTKGP SVFPLAPSSK STSGGTAALG CLVKDYFPEP V TVSWNSGA LTSGVHTFPA VLQSSGLYSL SSVVTVPSSS LGTQTYICNV NHKPSNTKVD KKVEPKSC

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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: 24 / 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

Concentration5.6 mg/mL
BufferpH: 7.4
GridModel: UltrAuFoil R1.2/1.3 / Support film - Material: GOLD / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV

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Electron microscopy

MicroscopeTFS GLACIOS
Image recordingFilm or detector model: TFS FALCON 4i (4k x 4k) / Average electron dose: 45.0 e/Å2
Electron beamAcceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.8 µm / Nominal defocus min: 0.8 µm / Nominal magnification: 190000
Sample stageSpecimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN

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Image processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: INSILICO MODEL / In silico model: ab initio model
Final reconstructionApplied symmetry - Point group: C3 (3 fold cyclic) / Resolution.type: BY AUTHOR / Resolution: 3.4 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 51495
Initial angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC
Final angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC
FSC plot (resolution estimation)

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