|Entry||Database: EMDB / ID: EMD-22940|
|Title||H5 hemagglutinin ectodomain bound to 3 polyclonal Fab fragments elicited by the qsMosaic-I53_dn5 immunogen|
|Sample||H5 hemagglutinin ectodomain bound to 3 polyclonal Fab fragments elicited by the qsMosaic-I53_dn5 immunogen|
|Biological species||unidentified influenza virus / Macaca mulatta (Rhesus monkey)|
|Method||single particle reconstruction / cryo EM / Resolution: 3.6 Å|
|Authors||Park YJ / Veesler D|
|Funding support|| United States, 1 items |
|Citation||Journal: Nature / Year: 2021|
Title: Quadrivalent influenza nanoparticle vaccines induce broad protection.
Authors: Seyhan Boyoglu-Barnum / Daniel Ellis / Rebecca A Gillespie / Geoffrey B Hutchinson / Young-Jun Park / Syed M Moin / Oliver J Acton / Rashmi Ravichandran / Mike Murphy / Deleah Pettie / Nick ...Authors: Seyhan Boyoglu-Barnum / Daniel Ellis / Rebecca A Gillespie / Geoffrey B Hutchinson / Young-Jun Park / Syed M Moin / Oliver J Acton / Rashmi Ravichandran / Mike Murphy / Deleah Pettie / Nick Matheson / Lauren Carter / Adrian Creanga / Michael J Watson / Sally Kephart / Sila Ataca / John R Vaile / George Ueda / Michelle C Crank / Lance Stewart / Kelly K Lee / Miklos Guttman / David Baker / John R Mascola / David Veesler / Barney S Graham / Neil P King / Masaru Kanekiyo /
Abstract: Influenza vaccines that confer broad and durable protection against diverse viral strains would have a major effect on global health, as they would lessen the need for annual vaccine reformulation ...Influenza vaccines that confer broad and durable protection against diverse viral strains would have a major effect on global health, as they would lessen the need for annual vaccine reformulation and immunization. Here we show that computationally designed, two-component nanoparticle immunogens induce potently neutralizing and broadly protective antibody responses against a wide variety of influenza viruses. The nanoparticle immunogens contain 20 haemagglutinin glycoprotein trimers in an ordered array, and their assembly in vitro enables the precisely controlled co-display of multiple distinct haemagglutinin proteins in defined ratios. Nanoparticle immunogens that co-display the four haemagglutinins of licensed quadrivalent influenza vaccines elicited antibody responses in several animal models against vaccine-matched strains that were equivalent to or better than commercial quadrivalent influenza vaccines, and simultaneously induced broadly protective antibody responses to heterologous viruses by targeting the subdominant yet conserved haemagglutinin stem. The combination of potent receptor-blocking and cross-reactive stem-directed antibodies induced by the nanoparticle immunogens makes them attractive candidates for a supraseasonal influenza vaccine candidate with the potential to replace conventional seasonal vaccines.
|Validation Report||Summary, Full report, XML, About validation report|
|Structure viewer||EM map: |
Downloads & links
|File||Download / File: emd_22940.map.gz / Format: CCP4 / Size: 244.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)|
|Projections & slices|
Images are generated by Spider.
|Voxel size||X=Y=Z: 1.05 Å|
|Symmetry||Space group: 1|
CCP4 map header:
-Additional map: #1
|Projections & Slices|
-Half map: #2
|Projections & Slices|
-Half map: #1
-Entire H5 hemagglutinin ectodomain bound to 3 polyclonal Fab fragments e...
|Entire||Name: H5 hemagglutinin ectodomain bound to 3 polyclonal Fab fragments elicited by the qsMosaic-I53_dn5 immunogen|
Number of components: 3
-Component #1: protein, H5 hemagglutinin ectodomain bound to 3 polyclonal Fab fr...
|Protein||Name: H5 hemagglutinin ectodomain bound to 3 polyclonal Fab fragments elicited by the qsMosaic-I53_dn5 immunogen|
Recombinant expression: No
-Component #2: protein, H5 hemagglutinin ectodomain
|Protein||Name: H5 hemagglutinin ectodomain / Recombinant expression: No|
|Source||Species: unidentified influenza virus|
|Source (engineered)||Expression System: Homo sapiens (human)|
-Component #3: protein, Polyclonal Fab fragments elicited by the qsMosaic-I53_dn...
|Protein||Name: Polyclonal Fab fragments elicited by the qsMosaic-I53_dn5 immunogen|
Recombinant expression: No
|Source||Species: Macaca mulatta (Rhesus monkey)|
|Specimen||Specimen state: Particle / Method: cryo EM|
|Sample solution||Specimen conc.: 1 mg/mL / pH: 8|
|Vitrification||Cryogen name: ETHANE|
-Electron microscopy imaging
Model: Titan Krios / Image courtesy: FEI Company
|Imaging||Microscope: FEI TITAN KRIOS|
|Electron gun||Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Electron dose: 70 e/Å2 / Illumination mode: FLOOD BEAM|
|Lens||Imaging mode: BRIGHT FIELD|
|Specimen Holder||Model: OTHER|
|Camera||Detector: GATAN K2 SUMMIT (4k x 4k)|
|Processing||Method: single particle reconstruction / Number of projections: 36783|
|3D reconstruction||Software: cryoSPARC / Resolution: 3.6 Å / Resolution method: FSC 0.143 CUT-OFF|
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