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- EMDB-42521: Structure of Lassa virus glycoprotein (Josiah) on the surface of ... -

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Entry
Database: EMDB / ID: EMD-42521
TitleStructure of Lassa virus glycoprotein (Josiah) on the surface of VSVdG-Lassa-GPC vaccine particle.
Map datamain map
Sample
  • Virus: Lassa virus Josiah
KeywordsViral glycoprotein / Lassa virus (Josiah) / VSV vaccine particle / VIRAL PROTEIN
Biological speciesLassa virus Josiah
Methodsingle particle reconstruction / negative staining / Resolution: 14.0 Å
AuthorsEnriquez AS / Saphire EO
Funding support United States, 2 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)R01 A1132244 United States
Other privateA08154 United States
CitationJournal: EBioMedicine / Year: 2025
Title: Preclinical development of a replication-competent vesicular stomatitis virus-based Lassa virus vaccine candidate advanced into human clinical trials.
Authors: Christopher L Cooper / Gavin Morrow / Maoli Yuan / Thomas S Postler / Maxwell L Neal / Robert W Cross / Courtney Woolsey / Krystle N Agans / Viktoriya Borisevich / Ryan P McNamara / Caroline ...Authors: Christopher L Cooper / Gavin Morrow / Maoli Yuan / Thomas S Postler / Maxwell L Neal / Robert W Cross / Courtney Woolsey / Krystle N Agans / Viktoriya Borisevich / Ryan P McNamara / Caroline Atyeo / Vicky Roy / Daritza Germosen / Fuxiang Hou / Shui L Li / Lucia Reiserova / Yesle Choi / Aaron Wilson / Denise Wagner / Olivia Wallace-Selman / Alexei Carpov / Fuqiang Geng / Deborah J Frederick / Joanne DeStefano / Anne M Ercolini / Adrian S Enriquez / Kathryn M Hastie / Suzane Ramos da Silva / Eddy Sayeed / John W Coleman / Andrew Kilianski / Galit Alter / Erica Ollmann Saphire / John D Aitchison / Thomas W Geisbert / Swati B Gupta / Mark B Feinberg / Christopher L Parks /
Abstract: BACKGROUND: Lassa fever (LF) is a zoonotic haemorrhagic disease caused by Lassa virus (LASV), which is endemic in West African countries. The multimammate rat is the main animal reservoir and its ...BACKGROUND: Lassa fever (LF) is a zoonotic haemorrhagic disease caused by Lassa virus (LASV), which is endemic in West African countries. The multimammate rat is the main animal reservoir and its geographic range is expected to expand due to influences like climate change and land usage, and this will place larger parts of Africa at risk. We conducted preclinical development on a promising experimental vaccine that allowed its advancement into human trials.
METHODS: The LF vaccine is based on a vesicular stomatitis virus (VSV) vector in which the VSV glycoprotein (G) was replaced with the LASV glycoprotein complex (GPC). Earlier studies showed that this ...METHODS: The LF vaccine is based on a vesicular stomatitis virus (VSV) vector in which the VSV glycoprotein (G) was replaced with the LASV glycoprotein complex (GPC). Earlier studies showed that this vaccine (VSVΔG-LASV-GPC) was efficacious in macaques, thus we regenerated VSVΔG-LASV-GPC using laboratory and documentation practices required to support vaccine manufacturing and human trials. The efficacy of the clinical vaccine candidate was assessed in cynomolgus macaques and more extensive immunologic analysis was performed than previously to investigate immune responses associated with protection.
FINDINGS: A single VSVΔG-LASV-GPC vaccination elicited innate, humoural and cellular immune responses, prevented development of substantial LASV viraemia, and protected animals from disease. ...FINDINGS: A single VSVΔG-LASV-GPC vaccination elicited innate, humoural and cellular immune responses, prevented development of substantial LASV viraemia, and protected animals from disease. Vaccinated macaques developed polyfunctional antibodies and serum was shown to neutralize virus expressing GPCs representative of geographically diverse LASV lineages.
INTERPRETATION: The VSVΔG-LASV-GPC clinical candidate elicited immunity that protected 10 of 10 vaccinated macaques from disease supporting its use in a clinical development program, which recently ...INTERPRETATION: The VSVΔG-LASV-GPC clinical candidate elicited immunity that protected 10 of 10 vaccinated macaques from disease supporting its use in a clinical development program, which recently progressed to phase 2 clinical trials. Moreover, immunologic analysis showed that virus-neutralizing serum antibodies likely played a role in preventing LASV disease in vaccinated macaques.
FUNDING: This work was supported by the Coalition for Epidemic Preparedness Innovations (CEPI), The National Institute of Allergy and Infectious Diseases (NIAID)/National Institutes of Health (NIH), ...FUNDING: This work was supported by the Coalition for Epidemic Preparedness Innovations (CEPI), The National Institute of Allergy and Infectious Diseases (NIAID)/National Institutes of Health (NIH), The Bill and Melinda Gates Global Vaccine Accelerator Program, the Burroughs Wellcome Fund, and financial gifts and support by Nancy Zimmerman, Mark and Lisa Schwartz, and Terry and Susan Ragon.
History
DepositionOct 30, 2023-
Header (metadata) releaseApr 9, 2025-
Map releaseApr 9, 2025-
UpdateApr 9, 2025-
Current statusApr 9, 2025Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_42521.png

Downloads & links

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Map

FileDownload / File: emd_42521.map.gz / Format: CCP4 / Size: 8 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Annotationmain map
Projections & slices

Image control

Size
Brightness
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Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.7 Å/pix.
x 128 pix.
= 217.6 Å		1.7 Å/pix.
x 128 pix.
= 217.6 Å		1.7 Å/pix.
x 128 pix.
= 217.6 Å

Surface

Projections

Slices (1/3)

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Images are generated by Spider.

Voxel sizeX=Y=Z: 1.7 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.22
Minimum - Maximum0.0 - 1.924283
Average (Standard dev.)0.016770788 (±0.11828502)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions128128128
Spacing128128128
CellA=B=C: 217.6 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: half map A

Fileemd_42521_half_map_1.map
Annotationhalf map A
Projections & Slices
AxesZYX

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Density Histograms

Histogram

Histogram (log scale)

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Half map: half map B

Fileemd_42521_half_map_2.map
Annotationhalf map B
Projections & Slices
AxesZYX

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Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Sample components

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Entire : Lassa virus Josiah

EntireName: Lassa virus Josiah
Components
  • Virus: Lassa virus Josiah

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Supramolecule #1: Lassa virus Josiah

SupramoleculeName: Lassa virus Josiah / type: virus / ID: 1 / Parent: 0 / NCBI-ID: 11622 / Sci species name: Lassa virus Josiah / Virus type: VIRION / Virus isolate: STRAIN / Virus enveloped: Yes / Virus empty: No
Host (natural)Organism: Mastomys natalensis (African soft-furred rat)

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Experimental details

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Structure determination

Methodnegative staining
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

BufferpH: 7.2
Details: Hank's Balanced Salt Solution pH 7.2 with 15% Trehalose (mass/volume)
StainingType: NEGATIVE / Material: Methylamine Tungstate
GridMaterial: COPPER / Mesh: 400 / Support film - Material: CARBON / Support film - topology: CONTINUOUS / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 15 sec. / Pretreatment - Atmosphere: OTHER
DetailsThis sample was monodisperse

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Electron microscopy

MicroscopeFEI TITAN
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 50.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.5 µm / Nominal defocus min: 1.0 µm

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Image processing

Startup modelType of model: INSILICO MODEL
Final reconstructionResolution.type: BY AUTHOR / Resolution: 14.0 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 914
Initial angle assignmentType: PROJECTION MATCHING
Final angle assignmentType: PROJECTION MATCHING

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