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- EMDB-73108: RQd20_wk56_28 Fab in complex with V703-0537_L14 SOSIP and 3BNC117 Fab -

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Basic information

Entry
Database: EMDB / ID: EMD-73108
TitleRQd20_wk56_28 Fab in complex with V703-0537_L14 SOSIP and 3BNC117 Fab
Map datasharpened map
Sample
  • Complex: RQd20_wk56_28 Fab in complex with V703-0537_L14 SOSIP and 3BNC117 Fab
    • Protein or peptide: 3BNC117 Fab heavy chain
    • Protein or peptide: 3BNC117 light chain
    • Protein or peptide: RQd20_wk56_28 Fab heavy chain
    • Protein or peptide: RQd20_wk56_28 light chain
    • Protein or peptide: V703-0537_L14 SOSIP
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
KeywordsHIV-1 / Env / NHP / V3 glycan / BG18 / germline targeting / VIRAL PROTEIN-IMMUNE SYSTEM complex
Biological speciesHuman immunodeficiency virus 1 / Homo sapiens (human) / Macaca mulatta (Rhesus monkey)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.4 Å
AuthorsPhulera S / 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: Nature / Year: 2026
Title: Vaccination elicits HIV broadly neutralizing antibodies in primates.
Authors: Jon M Steichen / Patrick J Madden / Claudia T Flynn / Swastik Phulera / Monolina Shil / Oleksandr Kalyuzhniy / Alessia Liguori / Carolyne Kifude / Leigh M Sewall / Christopher A Cottrell / ...Authors: Jon M Steichen / Patrick J Madden / Claudia T Flynn / Swastik Phulera / Monolina Shil / Oleksandr Kalyuzhniy / Alessia Liguori / Carolyne Kifude / Leigh M Sewall / Christopher A Cottrell / Krystal M Ma / Sabyasachi Baboo / Jolene K Diedrich / Katherine McKenney / Allan C deCamp / Diane G Carnathan / Ivy Phung / Parham Ramezani-Rad / Ester Marina-Zárate / Brian Freeman / Zhenfei Xie / Jeong Hyun Lee / Troy Sincomb / Nicole Phelps / Danny Lu / Diana Goodwin / Ryan Tingle / Yumiko Adachi / Nushin Alavi / Jenny Tran / Andy S Tran / Alyne Nascimento / Catherine Sovie / Daniel L V Bader / Hannah Voic / Xiaoya Zhou / Grace Pixton / Agnes Walsh / Mariane B Melo / Torben Schiffner / Facundo D Batista / Dennis R Burton / Darrell J Irvine / James C Paulson / John R Yates / Gabriel Ozorowski / Andrew B Ward / Guido Silvestri / Shane Crotty / William R Schief /
Abstract: The high antigenic diversity of HIV has been a major obstacle to development of a broadly protective vaccine. Nevertheless, protective HIV broadly neutralizing antibodies (bnAbs) exist and have been ...The high antigenic diversity of HIV has been a major obstacle to development of a broadly protective vaccine. Nevertheless, protective HIV broadly neutralizing antibodies (bnAbs) exist and have been proposed as templates for vaccine development. Germline targeting is a conceptually radical vaccine design approach to elicit bnAbs, aiming to prime rare bnAb-precursor B cells possessing predetermined human genetic and structural features shared with template bnAbs, and then guide B cell affinity maturation to potent bnAb evolution with heterologous boosters. Although the approach has shown promise in clinical and preclinical studies, it faces many immunological challenges and, to date, has not succeeded in generating bnAbs in humans or non-transgenic animals. Here we report testing of an adjuvanted protein germline-targeting vaccine in outbred non-human primates. The vaccine generated bnAb-class memory B cells and sera capable of neutralizing diverse HIV clinical isolates. bnAb lineages were generated in at least 50% of animals, achieving up to 67% neutralization breadth compared with the reference bnAb. Vaccine-induced bnAbs exhibited precise structural mimicry of human bnAb interactions with HIV envelope (Env), matching the germline-targeting predictions. Furthermore, serum bnAb activity developed in 44% of animals and in one instance reached titres expected to confer protection against diverse HIV isolates. These results demonstrate proof of principle that germline-targeting vaccines can reproducibly elicit prespecified classes of bnAbs to prespecified epitopes under endogenous conditions, supporting further optimization of this approach for HIV vaccine development.
History
DepositionOct 10, 2025-
Header (metadata) releaseJul 8, 2026-
Map releaseJul 8, 2026-
UpdateJul 15, 2026-
Current statusJul 15, 2026Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_73108.png

Downloads & links

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Map

FileDownload / File: emd_73108.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: 0.15
Minimum - Maximum-0.544 - 0.98403054
Average (Standard dev.)-0.000091027 (±0.019347105)
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_73108_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_73108_half_map_1.map
Annotationhalf map B
Projections & Slices
AxesZYX

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Density Histograms

Histogram

Histogram (log scale)

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Half map: half map A

Fileemd_73108_half_map_2.map
Annotationhalf map A
Projections & Slices
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Sample components

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Entire : RQd20_wk56_28 Fab in complex with V703-0537_L14 SOSIP and 3BNC117 Fab

EntireName: RQd20_wk56_28 Fab in complex with V703-0537_L14 SOSIP and 3BNC117 Fab
Components
  • Complex: RQd20_wk56_28 Fab in complex with V703-0537_L14 SOSIP and 3BNC117 Fab
    • Protein or peptide: 3BNC117 Fab heavy chain
    • Protein or peptide: 3BNC117 light chain
    • Protein or peptide: RQd20_wk56_28 Fab heavy chain
    • Protein or peptide: RQd20_wk56_28 light chain
    • Protein or peptide: V703-0537_L14 SOSIP
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose

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Supramolecule #1: RQd20_wk56_28 Fab in complex with V703-0537_L14 SOSIP and 3BNC117 Fab

SupramoleculeName: RQd20_wk56_28 Fab in complex with V703-0537_L14 SOSIP and 3BNC117 Fab
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#5
Source (natural)Organism: Human immunodeficiency virus 1

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Macromolecule #1: 3BNC117 Fab heavy chain

MacromoleculeName: 3BNC117 Fab heavy chain / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 24.656484 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: QVQLLQSGAA VTKPGASVRV SCEASGYNIR DYFIHWWRQA PGQGLQWVGW INPKTGQPNN PRQFQGRVSL TRHASWDFDT YSFYMDLKA LRSDDTAVYF CARQRSDYWD FDVWGSGTQV TVSSASTKGP SVFPLAPSSK STSGGTAALG CLVKDYFPEP V TVSWNSGA ...String:
QVQLLQSGAA VTKPGASVRV SCEASGYNIR DYFIHWWRQA PGQGLQWVGW INPKTGQPNN PRQFQGRVSL TRHASWDFDT YSFYMDLKA LRSDDTAVYF CARQRSDYWD FDVWGSGTQV TVSSASTKGP SVFPLAPSSK STSGGTAALG CLVKDYFPEP V TVSWNSGA LTSGVHTFPA VLQSSGLYSL SSVVTVPSSS LGTQTYICNV NHKPSNTKVD KKVEPKSC

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Macromolecule #2: 3BNC117 light chain

MacromoleculeName: 3BNC117 light chain / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 23.022658 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: DIQMTQSPSS LSASVGDTVT ITCQANGYLN WYQQRRGKAP KLLIYDGSKL ERGVPSRFSG RRWGQEYNLT INNLQPEDIA TYFCQVYEF VVPGTRLDLK RTVAAPSVFI FPPSDEQLKS GTASVVCLLN NFYPREAKVQ WKVDNALQSG NSQESVTEQD S KDSTYSLS ...String:
DIQMTQSPSS LSASVGDTVT ITCQANGYLN WYQQRRGKAP KLLIYDGSKL ERGVPSRFSG RRWGQEYNLT INNLQPEDIA TYFCQVYEF VVPGTRLDLK RTVAAPSVFI FPPSDEQLKS GTASVVCLLN NFYPREAKVQ WKVDNALQSG NSQESVTEQD S KDSTYSLS STLTLSKADY EKHKVYACEV THQGLSSPVT KSFNRGEC

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Macromolecule #3: RQd20_wk56_28 Fab heavy chain

MacromoleculeName: RQd20_wk56_28 Fab heavy chain / type: protein_or_peptide / ID: 3 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Macaca mulatta (Rhesus monkey)
Molecular weightTheoretical: 24.55765 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: QVHLQESGPG LVKPGETLSL TCGLSGAAIR DWWWTWVRQA PGKGLEWIGE IYGRDGSTHY NPSLKSRVTI SRDASKNHFS LRVTSVTAA DTAVYFCARV GPIYGVVFLG EFYHGFESWG QGVVVAVSSA STKGPSVFPL APSSKSTSGG TAALGCLVKD Y FPEPVTVS ...String:
QVHLQESGPG LVKPGETLSL TCGLSGAAIR DWWWTWVRQA PGKGLEWIGE IYGRDGSTHY NPSLKSRVTI SRDASKNHFS LRVTSVTAA DTAVYFCARV GPIYGVVFLG EFYHGFESWG QGVVVAVSSA STKGPSVFPL APSSKSTSGG TAALGCLVKD Y FPEPVTVS WNSGALTSGV HTFPAVLQSS GLYSLSSVVT VPSSSLGTQT YICNVNHKPS NTKVDKKVEP KSC

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Macromolecule #4: RQd20_wk56_28 light chain

MacromoleculeName: RQd20_wk56_28 light chain / type: protein_or_peptide / ID: 4 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Macaca mulatta (Rhesus monkey)
Molecular weightTheoretical: 22.838182 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: SFELTQPPSV SAASGQTAKI TCGGDNIGSL SVHWYQQSPP QAPVVLIYRD YRRPSGIPER FSGSHSGNTA TLTINRVEAG DEADYYCQV WDSNNYIFGT GTRLTVLGQP KAAPSVTLFP PSSEELQANK ATLVCLISDF YPGAVTVAWK ADSSPVKAGV E TTTPSKQS ...String:
SFELTQPPSV SAASGQTAKI TCGGDNIGSL SVHWYQQSPP QAPVVLIYRD YRRPSGIPER FSGSHSGNTA TLTINRVEAG DEADYYCQV WDSNNYIFGT GTRLTVLGQP KAAPSVTLFP PSSEELQANK ATLVCLISDF YPGAVTVAWK ADSSPVKAGV E TTTPSKQS NNKYAASSYL SLTPEQWKSH RSYSCQVTHE GSTVEKTVAP TECS

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Macromolecule #5: V703-0537_L14 SOSIP

MacromoleculeName: V703-0537_L14 SOSIP / type: protein_or_peptide / ID: 5 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Human immunodeficiency virus 1
Molecular weightTheoretical: 72.726281 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 SSENMTDNTK 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 #11: 2-acetamido-2-deoxy-beta-D-glucopyranose

MacromoleculeName: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 11 / Number of copies: 42 / 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

Concentration2.8 mg/mL
BufferpH: 7.4
GridModel: UltrAuFoil R1.2/1.3 / Material: GOLD / Mesh: 300 / 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
Sample stageSpecimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER

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Image processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: INSILICO MODEL / In silico model: cryoSPARC ab initio
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: 36490
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
FSC plot (resolution estimation)

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