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- EMDB-23098: Cryo-EM structure of the VRC316 clinical trial, vaccine-elicited,... -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-23098 | |||||||||
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Title | Cryo-EM structure of the VRC316 clinical trial, vaccine-elicited, human antibody 316-310-1B11 in complex with an H2 CAN05 HA trimer | |||||||||
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Function / homology | ![]() viral budding from plasma membrane / clathrin-dependent endocytosis of virus by host cell / membrane => GO:0016020 / host cell surface receptor binding / apical plasma membrane / fusion of virus membrane with host plasma membrane / fusion of virus membrane with host endosome membrane / viral envelope / virion attachment to host cell / host cell plasma membrane / virion membrane Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.85 Å | |||||||||
![]() | Gorman J / Kwong PD | |||||||||
Funding support | ![]()
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![]() | ![]() Title: A single residue in influenza virus H2 hemagglutinin enhances the breadth of the B cell response elicited by H2 vaccination. Authors: Sarah F Andrews / Julie E Raab / Jason Gorman / Rebecca A Gillespie / Crystal S F Cheung / Reda Rawi / Lauren Y Cominsky / Jeffrey C Boyington / Adrian Creanga / Chen-Hsiang Shen / Darcy R ...Authors: Sarah F Andrews / Julie E Raab / Jason Gorman / Rebecca A Gillespie / Crystal S F Cheung / Reda Rawi / Lauren Y Cominsky / Jeffrey C Boyington / Adrian Creanga / Chen-Hsiang Shen / Darcy R Harris / Adam S Olia / Alexandra F Nazzari / Tongqing Zhou / Katherine V Houser / Grace L Chen / John R Mascola / Barney S Graham / Masaru Kanekiyo / Julie E Ledgerwood / Peter D Kwong / Adrian B McDermott / ![]() Abstract: Conserved epitopes on the influenza hemagglutinin (HA) stem are an attractive target for universal vaccine strategies as they elicit broadly neutralizing antibodies. Such antibody responses to stem- ...Conserved epitopes on the influenza hemagglutinin (HA) stem are an attractive target for universal vaccine strategies as they elicit broadly neutralizing antibodies. Such antibody responses to stem-specific epitopes have been extensively characterized for HA subtypes H1 and H5 in humans. H2N2 influenza virus circulated 50 years ago and represents a pandemic threat due to the lack of widespread immunity, but, unlike H1 and H5, the H2 HA stem contains Phe45 predicted to sterically clash with HA stem-binding antibodies characterized to date. To understand the effect of Phe45, we compared the HA stem-specific B cell response in post hoc analyses of two phase 1 clinical trials, one testing vaccination with an H2 ferritin nanoparticle immunogen ( NCT03186781 ) and one with an inactivated H5N1 vaccine ( NCT01086657 ). In H2-naive individuals, the magnitude of the B cell response was equivalent, but H2-elicited HA stem-binding B cells displayed greater cross-reactivity than those elicited by H5. However, in individuals with childhood H2 exposure, H5-elicited HA stem-binding B cells also displayed high cross-reactivity, suggesting recall of memory B cells formed 50 years ago. Overall, we propose that a one-residue difference on an HA immunogen can alter establishment and expansion of broadly neutralizing memory B cells. These data have implications for stem-based universal influenza vaccination strategies. | |||||||||
History |
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Structure visualization
Movie |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 116.8 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 25.9 KB 25.9 KB | Display Display | ![]() |
Images | ![]() | 119.3 KB | ||
Masks | ![]() | 125 MB | ![]() | |
Others | ![]() ![]() ![]() ![]() | 31.3 MB 16.8 MB 116 MB 116 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 790.1 KB | Display | ![]() |
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Full document | ![]() | 789.7 KB | Display | |
Data in XML | ![]() | 13.8 KB | Display | |
Data in CIF | ![]() | 16.3 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7l0lMC ![]() 7mfgC M: atomic model generated by this map C: citing same article ( |
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Similar structure data |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Annotation | Sharpened map | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.083 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Mask #1
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Density Histograms |
-Additional map: unsharpened map
File | emd_23098_additional_1.map | ||||||||||||
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Annotation | unsharpened map | ||||||||||||
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Density Histograms |
-Additional map: density modified map with resolve
File | emd_23098_additional_2.map | ||||||||||||
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Annotation | density modified map with resolve | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: half map A
File | emd_23098_half_map_1.map | ||||||||||||
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Annotation | half map A | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: half map B
File | emd_23098_half_map_2.map | ||||||||||||
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Annotation | half map B | ||||||||||||
Projections & Slices |
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Density Histograms |
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Sample components
-Entire : 316-310-1B11 Fab in complex with an H2 CAN05 HA trimer
Entire | Name: 316-310-1B11 Fab in complex with an H2 CAN05 HA trimer |
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Components |
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-Supramolecule #1: 316-310-1B11 Fab in complex with an H2 CAN05 HA trimer
Supramolecule | Name: 316-310-1B11 Fab in complex with an H2 CAN05 HA trimer type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#4 |
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Source (natural) | Organism: ![]() ![]() |
Recombinant expression | Organism: ![]() |
-Macromolecule #1: 316-310-1B11 Light Chain
Macromolecule | Name: 316-310-1B11 Light Chain / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 23.460025 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: EIVLTQSPGT LSLSPGDRAT LSCRASQSVP SSYLAWYRHK PGQAPRLLIY GASSRATGIP DRFSGSGSGT DFSLTISRVE PEDFAVYYC QQYGSSPYTF GRGTKLDIKR TVAAPSVFIF PPSDEQLKSG TASVVCLLNN FYPREAKVQW KVDNALQSGN S QESVTEQD ...String: EIVLTQSPGT LSLSPGDRAT LSCRASQSVP SSYLAWYRHK PGQAPRLLIY GASSRATGIP DRFSGSGSGT DFSLTISRVE PEDFAVYYC QQYGSSPYTF GRGTKLDIKR TVAAPSVFIF PPSDEQLKSG TASVVCLLNN FYPREAKVQW KVDNALQSGN S QESVTEQD SKDSTYSLSS TLTLSKADYE KHKVYACEVT HQGLSSPVTK SFNRGEC |
-Macromolecule #2: Hemagglutinin HA1 chain
Macromolecule | Name: Hemagglutinin HA1 chain / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 38.802152 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MAIIYLILLF TAVRGDQICI GYHANNSTEK VDTICERNVT VTHAKDILEK THNGKLCKLN GIPPLELGDC SIAGWLLGNP ECDRLLSVP EWSYIMEKEN PRDGLCYPGS FNDYEELKHL LSSVKHFEKV KILPKDRWTQ HTTTGGSRAC AVSGNPSFFR N MVWLTKKG ...String: MAIIYLILLF TAVRGDQICI GYHANNSTEK VDTICERNVT VTHAKDILEK THNGKLCKLN GIPPLELGDC SIAGWLLGNP ECDRLLSVP EWSYIMEKEN PRDGLCYPGS FNDYEELKHL LSSVKHFEKV KILPKDRWTQ HTTTGGSRAC AVSGNPSFFR N MVWLTKKG SNYPVAQGSY NNTSGEQMLI IWGVHHPNDE TEQRTLYQNV GTYVSVGTST LNKRSTPEIA TRPKVNGQGG RM EFSWTLL DMWDTINFES TGNLIAPEYG FKISKRGSSG IMKTEGTLEN CETKCQTPLG AINTTLPFHN VHPLTIGECP KYV KSEKLV LATGLRNVPQ IESRRRRRR |
-Macromolecule #3: Hemagglutinin HA2 chain
Macromolecule | Name: Hemagglutinin HA2 chain / type: protein_or_peptide / ID: 3 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 25.489357 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: GLFGAIAGFI EGGWQGMVDG WYGYHHSNDQ GSGYAADKES TQKAFDCITN KVNSVIEKMN TQFEAVGKEF SNLERRLENL NKKMEDGFL DVWTYNAELL VLMENERTLD FHDSNVKNLY DKVRMQLRDN VKELGNGCFE FYHKCDDECM NSVKNGTYDY P KYEEESKL ...String: GLFGAIAGFI EGGWQGMVDG WYGYHHSNDQ GSGYAADKES TQKAFDCITN KVNSVIEKMN TQFEAVGKEF SNLERRLENL NKKMEDGFL DVWTYNAELL VLMENERTLD FHDSNVKNLY DKVRMQLRDN VKELGNGCFE FYHKCDDECM NSVKNGTYDY P KYEEESKL NRNEIKGVKG RLVPRGSPGS GYIPEAPRDG QAYVRKDGEW VLLSTFLGHH HHHH |
-Macromolecule #4: 316-310-1B11 Heavy Chain
Macromolecule | Name: 316-310-1B11 Heavy Chain / type: protein_or_peptide / ID: 4 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 25.065092 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: QVQLVQSGAE VKKPGSSVKV SCKTSGGIFR SNAISWVRQA PGQGLEWMGG VVAIFGTTNY AQNFQGRVTI TADESSSTVY MELSRLRSE DTAVYYCARH SGYHITNTFF DYWGQGTLVT VSSASTKGPS VFPLAPSSKS TSGGTAALGC LVKDYFPEPV T VSWNSGAL ...String: QVQLVQSGAE VKKPGSSVKV SCKTSGGIFR SNAISWVRQA PGQGLEWMGG VVAIFGTTNY AQNFQGRVTI TADESSSTVY MELSRLRSE DTAVYYCARH SGYHITNTFF DYWGQGTLVT VSSASTKGPS VFPLAPSSKS TSGGTAALGC LVKDYFPEPV T VSWNSGAL TSGVHTFPAV LQSSGLYSLS SVVTVPSSSL GTQTYICNVN HKPSNTKVDK KVEPKSCDKG LEVLFQGP |
-Macromolecule #5: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 5 / Number of copies: 15 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ![]() ChemComp-NAG: |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 2 mg/mL |
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Buffer | pH: 7.4 / Component - Formula: PBS |
Grid | Model: C-flat-1.2/1.3 / Material: COPPER / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: PLASMA CLEANING |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 90 % / Chamber temperature: 293 K / Instrument: FEI VITROBOT MARK IV |
Details | Cryo-EM structure of the VRC316 clinical trial, vaccine-elicited, human antibody 316-310-1B11 in complex with an H2 CAN05 HA trimer |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Detector mode: COUNTING / Number grids imaged: 1 / Number real images: 2439 / Average electron dose: 51.16 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | C2 aperture diameter: 100.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |