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- PDB-8d21: Cryo-EM structure of the VRC321 clinical trial, vaccine-elicited,... -
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Open data
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Basic information
Entry | Database: PDB / ID: 8d21 | |||||||||
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Title | Cryo-EM structure of the VRC321 clinical trial, vaccine-elicited, human antibody 1B06 in complex with a stabilized NC99 HA trimer | |||||||||
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![]() | IMMUNE SYSTEM/Viral Protein / VRC / IMMUNE SYSTEM / VRC321 / Fab / Stem / IMMUNE SYSTEM-Viral Protein complex | |||||||||
Function / homology | ![]() viral budding from plasma membrane / clathrin-dependent endocytosis of virus by host cell / 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 / membrane Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.96 Å | |||||||||
![]() | Gorman, J. / Kwong, P.D. | |||||||||
Funding support | ![]()
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![]() | ![]() Title: An influenza H1 hemagglutinin stem-only immunogen elicits a broadly cross-reactive B cell response in humans. Authors: Sarah F Andrews / Lauren Y Cominsky / Geoffrey D Shimberg / Rebecca A Gillespie / Jason Gorman / Julie E Raab / Joshua Brand / Adrian Creanga / Suprabhath R Gajjala / Sandeep Narpala / ...Authors: Sarah F Andrews / Lauren Y Cominsky / Geoffrey D Shimberg / Rebecca A Gillespie / Jason Gorman / Julie E Raab / Joshua Brand / Adrian Creanga / Suprabhath R Gajjala / Sandeep Narpala / Crystal S F Cheung / Darcy R Harris / Tongqing Zhou / Ingelise Gordon / LaSonji Holman / Floreliz Mendoza / Katherine V Houser / Grace L Chen / John R Mascola / Barney S Graham / Peter D Kwong / Alicia Widge / Lesia K Dropulic / Julie E Ledgerwood / Masaru Kanekiyo / Adrian B McDermott / ![]() Abstract: Current yearly seasonal influenza vaccines primarily induce an antibody response directed against the immunodominant but continually diversifying hemagglutinin (HA) head region. These antibody ...Current yearly seasonal influenza vaccines primarily induce an antibody response directed against the immunodominant but continually diversifying hemagglutinin (HA) head region. These antibody responses provide protection against the vaccinating strain but little cross-protection against other influenza strains or subtypes. To focus the immune response on subdominant but more conserved epitopes on the HA stem that might protect against a broad range of influenza strains, we developed a stabilized H1 stem immunogen lacking the immunodominant head displayed on a ferritin nanoparticle (H1ssF). Here, we evaluated the B cell response to H1ssF in healthy adults ages 18 to 70 in a phase 1 clinical trial (NCT03814720). We observed both a strong plasmablast response and sustained elicitation of cross-reactive HA stem-specific memory B cells after vaccination with H1ssF in individuals of all ages. The B cell response was focused on two conserved epitopes on the H1 stem, with a highly restricted immunoglobulin repertoire unique to each epitope. On average, two-thirds of the B cell and serological antibody response recognized a central epitope on the H1 stem and exhibited broad neutralization across group 1 influenza virus subtypes. The remaining third recognized an epitope near the viral membrane anchor and was largely limited to H1 strains. Together, we demonstrate that an H1 HA immunogen lacking the immunodominant HA head produces a robust and broadly neutralizing HA stem-directed B cell response. | |||||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 387.4 KB | Display | ![]() |
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PDB format | ![]() | 323.4 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 27139MC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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1 |
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Components
-Hemagglutinin ... , 2 types, 6 molecules BCGADI
#1: Protein | Mass: 25263.104 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #2: Protein | Mass: 36407.852 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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-Antibody , 2 types, 6 molecules HEJLFK
#3: Antibody | Mass: 13499.133 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() #4: Antibody | Mass: 11778.080 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
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-Sugars , 2 types, 24 molecules ![](data/chem/img/NAG.gif)
#5: Polysaccharide | Source method: isolated from a genetically manipulated source #6: Sugar | ChemComp-NAG / |
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-Details
Has ligand of interest | N |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component |
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Molecular weight | Experimental value: NO | ||||||||||||||||||
Source (natural) | Organism: ![]() ![]() | ||||||||||||||||||
Source (recombinant) | Organism: ![]() | ||||||||||||||||||
Buffer solution | pH: 7.4 / Details: PBS | ||||||||||||||||||
Specimen | Conc.: 2 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES / Details: 1B06 in complex with a stabilized NC99 HA trimer | ||||||||||||||||||
Specimen support | Grid type: C-flat-1.2/1.3 | ||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 90 % / Chamber temperature: 293 K |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2500 nm / Nominal defocus min: 1000 nm / C2 aperture diameter: 70 µm |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Average exposure time: 2 sec. / Electron dose: 70.72 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K3 (6k x 4k) / Num. of grids imaged: 1 |
Image scans | Movie frames/image: 50 |
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Processing
Software | Name: PHENIX / Version: 1.20_4459: / Classification: refinement | ||||||||||||||||||||||||
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EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
Symmetry | Point symmetry: C3 (3 fold cyclic) | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.96 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 73396 / Symmetry type: POINT | ||||||||||||||||||||||||
Atomic model building | Protocol: FLEXIBLE FIT / Space: REAL | ||||||||||||||||||||||||
Atomic model building | PDB-ID: 7MFG | ||||||||||||||||||||||||
Refine LS restraints |
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