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- EMDB-0350: Induction of Potent Neutralizing Antibody Responses by a Designed... -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-0350 | |||||||||
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Title | Induction of Potent Neutralizing Antibody Responses by a Designed Protein Nanoparticle Vaccine for Respiratory Syncytial Virus | |||||||||
![]() | DS-Cav1-I53-50 nanoparticle | |||||||||
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Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 6.3 Å | |||||||||
![]() | Marcandalli J / Fiala B / Ols S / Perotti M / van der Schueren W / Snijder S / Hodge E / Benhaim M / Ravichandran R / Carter L ...Marcandalli J / Fiala B / Ols S / Perotti M / van der Schueren W / Snijder S / Hodge E / Benhaim M / Ravichandran R / Carter L / Sheffler W / Brunner L / Lawrenz M / Dubois P / Lanzavecchia A / Sallusto F / Lee KK / Veesler D / Correnti CE / Stewart LJ / Baker D / Lore K / Perez L / King NP | |||||||||
![]() | ![]() Title: Induction of Potent Neutralizing Antibody Responses by a Designed Protein Nanoparticle Vaccine for Respiratory Syncytial Virus. Authors: Jessica Marcandalli / Brooke Fiala / Sebastian Ols / Michela Perotti / Willem de van der Schueren / Joost Snijder / Edgar Hodge / Mark Benhaim / Rashmi Ravichandran / Lauren Carter / Will ...Authors: Jessica Marcandalli / Brooke Fiala / Sebastian Ols / Michela Perotti / Willem de van der Schueren / Joost Snijder / Edgar Hodge / Mark Benhaim / Rashmi Ravichandran / Lauren Carter / Will Sheffler / Livia Brunner / Maria Lawrenz / Patrice Dubois / Antonio Lanzavecchia / Federica Sallusto / Kelly K Lee / David Veesler / Colin E Correnti / Lance J Stewart / David Baker / Karin Loré / Laurent Perez / Neil P King / ![]() ![]() ![]() ![]() ![]() Abstract: Respiratory syncytial virus (RSV) is a worldwide public health concern for which no vaccine is available. Elucidation of the prefusion structure of the RSV F glycoprotein and its identification as ...Respiratory syncytial virus (RSV) is a worldwide public health concern for which no vaccine is available. Elucidation of the prefusion structure of the RSV F glycoprotein and its identification as the main target of neutralizing antibodies have provided new opportunities for development of an effective vaccine. Here, we describe the structure-based design of a self-assembling protein nanoparticle presenting a prefusion-stabilized variant of the F glycoprotein trimer (DS-Cav1) in a repetitive array on the nanoparticle exterior. The two-component nature of the nanoparticle scaffold enabled the production of highly ordered, monodisperse immunogens that display DS-Cav1 at controllable density. In mice and nonhuman primates, the full-valency nanoparticle immunogen displaying 20 DS-Cav1 trimers induced neutralizing antibody responses ∼10-fold higher than trimeric DS-Cav1. These results motivate continued development of this promising nanoparticle RSV vaccine candidate and establish computationally designed two-component nanoparticles as a robust and customizable platform for structure-based vaccine design. | |||||||||
History |
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Structure visualization
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 4.2 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 11.9 KB 11.9 KB | Display Display | ![]() |
Images | ![]() | 181.8 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 78.8 KB | Display | ![]() |
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Full document | ![]() | 77.9 KB | Display | |
Data in XML | ![]() | 493 B | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
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 | DS-Cav1-I53-50 nanoparticle | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 2.5 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 : DS-Cav1-I53-50 nanoparticle
Entire | Name: DS-Cav1-I53-50 nanoparticle |
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Components |
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-Supramolecule #1: DS-Cav1-I53-50 nanoparticle
Supramolecule | Name: DS-Cav1-I53-50 nanoparticle / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: ![]() |
Recombinant expression | Organism: ![]() |
-Macromolecule #1: Engineered respiratory syncytial virus F protein (DS-Cav-1) fused...
Macromolecule | Name: Engineered respiratory syncytial virus F protein (DS-Cav-1) fused to the foldon and to the trimeric component of I53-50 (DS-Cav1-I53-50A) type: protein_or_peptide / ID: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Sequence | String: MELLILKANA ITTILTAVTF CFASGQNITE EFYQSTCSAV SKGYLSALRT GWYTSVITIE LSNIKENKCN GTDAKVKLIK QELDKYKNAV TELQLLMQST PATNNRARRE LPRFMNYTLN NAKKTNVTLS KKRKRRFLGF LLGVGSAIAS GVAVCKVLHL EGEVNKIKSA ...String: MELLILKANA ITTILTAVTF CFASGQNITE EFYQSTCSAV SKGYLSALRT GWYTSVITIE LSNIKENKCN GTDAKVKLIK QELDKYKNAV TELQLLMQST PATNNRARRE LPRFMNYTLN NAKKTNVTLS KKRKRRFLGF LLGVGSAIAS GVAVCKVLHL EGEVNKIKSA LLSTNKAVVS LSNGVSVLTF KVLDLKNYID KQLLPILNKQ SCSISNIETV IEFQQKNNRL LEITREFSVN AGVTTPVSTY MLTNSELLSL INDMPITNDQ KKLMSNNVQI VRQQSYSIMC IIKEEVLAYV VQLPLYGVID TPCWKLHTSP LCTTNTKEGS NICLTRTDRG WYCDNAGSVS FFPQAETCKV QSNRVFCDTM NSLTLPSEVN LCNVDIFNPK YDCKIMTSKT DVSSSVITSL GAIVSCYGKT KCTASNKNRG IIKTFSNGCD YVSNKGVDTV SVGNTLYYVN KQEGKSLYVK GEPIINFYDP LVFPSDEFDA SISQVNEKIN QSLAFIRGYI PEAPRDGQAY VRKDGEWVLL STFLGSGSHH HHHHHHGGSG GSGSEKAAKA EEAARKMEEL FKKHKIVAVL RANSVEEAIE KAVAVFAGGV HLIEITFTVP DADTVIKALS VLKEKGAIIG AGTVTSVEQC RKAVESGAEF IVSPHLDEEI SQFCKEKGVF YMPGVMTPTE LVKAMKLGHT ILKLFPGEVV GPQFVKAMKG PFPNVKFVPT GGVNLDNVCE WFKAGVLAVG VGSALVKGTP DEVREKAKAF VEKIRGCTE |
-Macromolecule #2: Pentameric component of I53-50 (I53-50B)
Macromolecule | Name: Pentameric component of I53-50 (I53-50B) / type: protein_or_peptide / ID: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Sequence | String: MNQHSHKDHE TVRIAVVRAR WHAEIVDACV SAFEAAMRDI GGDRFAVDVF DVPGAYEIPL HARTLAETGR YGAVLGTAFV VNGGIYRHEF VASAVINGMM NVQLNTGVPV LSAVLTPHNY DKSKAHTLLF LALFAVKGME AARACVEILA AREKIAAGSL EHHHHHH |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 8 |
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Grid | Details: unspecified |
Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TECNAI 20 |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 45.0 e/Å2 |
Electron beam | Acceleration voltage: 200 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
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Image processing
Startup model | Type of model: INSILICO MODEL / In silico model: Computationally designed model |
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Final reconstruction | Applied symmetry - Point group: I (icosahedral) / Resolution.type: BY AUTHOR / Resolution: 6.3 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 1200 |
Initial angle assignment | Type: PROJECTION MATCHING |
Final angle assignment | Type: PROJECTION MATCHING |