+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-50499 | |||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Title | Compact formalin inactivated CVB1 | |||||||||||||||
Map data | Density map of compact formalin inactivated CVB1 resolved at 4.1 A. | |||||||||||||||
Sample |
| |||||||||||||||
Keywords | coxsackievirus B1 / vaccine / formalin / VIRUS | |||||||||||||||
Biological species | Coxsackievirus B1 | |||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.1 Å | |||||||||||||||
Authors | Plavec Z / Butcher SJ | |||||||||||||||
Funding support | Finland, 4 items
| |||||||||||||||
Citation | Journal: Res Sq / Year: 2024 Title: Comparison of structure and immunogenicity of CVB1-VLP and inactivated CVB1 vaccine candidates. Authors: Saana Soppela / Zlatka Plavec / Stina Gröhn / Minne Jartti / Sami Oikarinen / Mira Laajala / Varpu Marjomaki / Sarah J Butcher / Minna M Hankaniemi Abstract: Coxsackievirus B1 (CVB1) is a common cause of acute and chronic myocarditis, dilated cardiomyopathy and aseptic meningitis. However, no CVB-vaccines are available for human use. In this study, we ...Coxsackievirus B1 (CVB1) is a common cause of acute and chronic myocarditis, dilated cardiomyopathy and aseptic meningitis. However, no CVB-vaccines are available for human use. In this study, we investigated the immunogenicity of virus-like particle (VLP) and inactivated whole-virus vaccines for CVB1 when administrated to mice via either subcutaneous or intranasal routes formulated with and without commercial and experimental adjuvants. Here, the potential of utilizing epigallocatechin-3-gallate (EGCG) as a mucosal adjuvant synergistically with its ability to inactivate the virus were investigated. EGCG had promising adjuvant properties for CVB1-VLP when administered via the parenteral route but limited efficacy via intranasal administration. However, intranasal administration of the formalin-inactivated virus induced high CVB1-specific humoral, cellular, and mucosal immune responses. Also, based on CVB1-specific IgG-antibody responses, we conclude that CVB1-VLP can be taken up by immune cells when administrated intranasally and further structural engineering for the VLP may increase the mucosal immunogenicity. The preparations contained mixtures of compact and expanded A particles with 85% expanded in the formalin-inactivated virus, but only 52% in the VLP observed by cryogenic electron microscopy. To correlate the structure to immunogenicity, we solved the structures of the CVB1-VLP and the formalin-inactivated CVB1 virus at resolutions ranging from 2.15 A to 4.1 A for the expanded and compact VLP and virus particles by image reconstruction. These structures can be used in designing mutations increasing the stability and immunogenicity of CVB1-VLP in the future. Overall, our results highlight the potential of using formalin inactivated CVB1 vaccine in mucosal immunization programs and provide important information for future development of VLP-based vaccines against all enteroviruses. | |||||||||||||||
History |
|
-Structure visualization
Supplemental images |
---|
-Downloads & links
-EMDB archive
Map data | emd_50499.map.gz | 172 MB | EMDB map data format | |
---|---|---|---|---|
Header (meta data) | emd-50499-v30.xml emd-50499.xml | 14.3 KB 14.3 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_50499_fsc.xml | 15 KB | Display | FSC data file |
Images | emd_50499.png | 65.9 KB | ||
Filedesc metadata | emd-50499.cif.gz | 4.2 KB | ||
Others | emd_50499_half_map_1.map.gz emd_50499_half_map_2.map.gz | 321.9 MB 322.1 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-50499 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-50499 | HTTPS FTP |
-Validation report
Summary document | emd_50499_validation.pdf.gz | 1.4 MB | Display | EMDB validaton report |
---|---|---|---|---|
Full document | emd_50499_full_validation.pdf.gz | 1.4 MB | Display | |
Data in XML | emd_50499_validation.xml.gz | 24.4 KB | Display | |
Data in CIF | emd_50499_validation.cif.gz | 31.7 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-50499 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-50499 | HTTPS FTP |
-Related structure data
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
---|
-Map
File | Download / File: emd_50499.map.gz / Format: CCP4 / Size: 347.6 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Density map of compact formalin inactivated CVB1 resolved at 4.1 A. | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.97 Å | ||||||||||||||||||||||||||||||||||||
Density |
| ||||||||||||||||||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
|
-Supplemental data
-Half map: Half map of compact formalin inactivated CVB1.
File | emd_50499_half_map_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Half map of compact formalin inactivated CVB1. | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: Half map of compact formalin inactivated CVB1.
File | emd_50499_half_map_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Half map of compact formalin inactivated CVB1. | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Sample components
-Entire : Coxsackievirus B1
Entire | Name: Coxsackievirus B1 |
---|---|
Components |
|
-Supramolecule #1: Coxsackievirus B1
Supramolecule | Name: Coxsackievirus B1 / type: virus / ID: 1 / Parent: 0 / Macromolecule list: #1-#4 Details: Coxsackievirus B1 (CVB1-10796, isolated from Argentina) NCBI-ID: 12071 / Sci species name: Coxsackievirus B1 / Virus type: VIRION / Virus isolate: OTHER / Virus enveloped: No / Virus empty: No |
---|---|
Host (natural) | Organism: Homo sapiens (human) |
Virus shell | Shell ID: 1 / Name: capsid / Diameter: 30.0 Å |
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.5 |
---|---|
Grid | Model: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 300 / Support film - Material: CARBON / Support film - topology: CONTINUOUS / Support film - Film thickness: 200 / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 10 sec. |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 85 % / Chamber temperature: 295 K / Instrument: LEICA EM GP |
-Electron microscopy
Microscope | FEI TALOS ARCTICA |
---|---|
Image recording | Film or detector model: FEI FALCON III (4k x 4k) / Detector mode: COUNTING / Average electron dose: 40.0 e/Å2 |
Electron beam | Acceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.8000000000000003 µm / Nominal defocus min: 0.1 µm / Nominal magnification: 150000 |
Experimental equipment | Model: Talos Arctica / Image courtesy: FEI Company |