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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-11398 | |||||||||
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Title | I5350 negative staining | |||||||||
![]() | I5350 Nanoparticle | |||||||||
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Biological species | ![]() | |||||||||
Method | single particle reconstruction / negative staining / Resolution: 20.0 Å | |||||||||
![]() | Perez L | |||||||||
![]() | ![]() Title: Rationally designed Human Cytomegalovirus gB nanoparticle vaccine with improved immunogenicity. Authors: Michela Perotti / Jessica Marcandalli / Davide Demurtas / Federica Sallusto / Laurent Perez / ![]() Abstract: Human cytomegalovirus (HCMV) is the primary viral cause of congenital birth defects and causes significant morbidity and mortality in immune-suppressed transplant recipients. Despite considerable ...Human cytomegalovirus (HCMV) is the primary viral cause of congenital birth defects and causes significant morbidity and mortality in immune-suppressed transplant recipients. Despite considerable efforts in vaccine development, HCMV infection still represents an unmet clinical need. In recent phase II trials, a MF59-adjuvanted gB vaccine showed only modest efficacy in preventing infection. These findings might be attributed to low level of antibodies (Abs) with a neutralizing activity induced by this vaccine. Here, we analyzed the immunogenicity of each gB antigenic domain (AD) and demonstrated that domain I of gB (AD5) is the main target of HCMV neutralizing antibodies. Furthermore, we designed, characterized and evaluated immunogenic responses to two different nanoparticles displaying a trimeric AD5 antigen. We showed that mice immunization with nanoparticles induces sera neutralization titers up to 100-fold higher compared to those obtained with the gB extracellular domain (gBECD). Collectively, these results illustrate with a medically relevant example the advantages of using a general approach combining antigen discovery, protein engineering and scaffold presentation for modern development of subunit vaccines against complex pathogens. | |||||||||
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 | ![]() | 227.8 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 9.5 KB 9.5 KB | Display Display | ![]() |
Images | ![]() | 71.5 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 293.5 KB | Display | ![]() |
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Full document | ![]() | 293.1 KB | Display | |
Data in XML | ![]() | 7.5 KB | Display | |
Data in CIF | ![]() | 8.6 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | C: citing same article ( |
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Similar structure data |
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Links
EMDB pages | ![]() ![]() |
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Map
File | ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | I5350 Nanoparticle | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 2.0625 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
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Sample components
-Entire : 53-50A in complex with I53-50B.4PT1
Entire | Name: 53-50A in complex with I53-50B.4PT1 |
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Components |
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-Supramolecule #1: 53-50A in complex with I53-50B.4PT1
Supramolecule | Name: 53-50A in complex with I53-50B.4PT1 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: ![]() |
Recombinant expression | Organism: ![]() |
-Macromolecule #1: I5350
Macromolecule | Name: I5350 / type: protein_or_peptide / ID: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Recombinant expression | Organism: ![]() |
Sequence | String: MKMEELFKKH KIVAVLRANS VEEAIEKAVA VFAGGVHLIE ITFTVPDADT VIKALSVLKE KGAIIGAGTV TSVEQCRKAV ESGAEFIVSP HLDEEISQFC KEKGVFYMPG VMTPTELVKA MKLGHTILKL FPGEVVGPQF VKAMKGPFPN VKFVPTGGV NLDNVCEWFK ...String: MKMEELFKKH KIVAVLRANS VEEAIEKAVA VFAGGVHLIE ITFTVPDADT VIKALSVLKE KGAIIGAGTV TSVEQCRKAV ESGAEFIVSP HLDEEISQFC KEKGVFYMPG VMTPTELVKA MKLGHTILKL FPGEVVGPQF VKAMKGPFPN VKFVPTGGV NLDNVCEWFK AGVLAVGVGS ALVKGTPDEV REKAKAFVEK IRGCTELEHH HHHH MNQHS HKDHETVRIA VVRARWHAEI VDACVSAFEA AMRDIGGDRF AVDVFDVPGA YEIPLHARTL AETGRYGAVL GT AFVVNGG IYRHEFVASA VINGMMNVQL NTGVPVLSAV LTPHNYDKSK AHTLLFLALF AVKGMEAARA CVEILAAREK I AAGSLEHH HHHH |
-Experimental details
-Structure determination
Method | negative staining |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 0.05 mg/mL |
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Buffer | pH: 7 |
Staining | Type: NEGATIVE / Material: uranyl acetate |
Grid | Model: Homemade / Material: COPPER / Mesh: 400 / Pretreatment - Type: GLOW DISCHARGE |
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Electron microscopy
Microscope | FEI TECNAI F20 |
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Image recording | Film or detector model: FEI FALCON III (4k x 4k) / Average electron dose: 70.0 e/Å2 |
Electron beam | Acceleration voltage: 200 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: OTHER / Cs: 2.26 mm |
Experimental equipment | ![]() Model: Tecnai F20 / Image courtesy: FEI Company |
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Image processing
CTF correction | Software - Name: cryoSPARC |
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Final reconstruction | Applied symmetry - Point group: D7 (2x7 fold dihedral) / Resolution.type: BY AUTHOR / Resolution: 20.0 Å / Resolution method: OTHER / Software - Name: cryoSPARC / Number images used: 8467 |
Initial angle assignment | Type: NOT APPLICABLE |
Final angle assignment | Type: NOT APPLICABLE |
-Atomic model buiding 1
Refinement | Protocol: AB INITIO MODEL |
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