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- EMDB-7004: Eilat virus/eastern equine encephalitis virus chimeric vaccine ca... -

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Basic information

Entry
Database: EMDB / ID: 7004
TitleEilat virus/eastern equine encephalitis virus chimeric vaccine candidate
Map dataEilat virus/eastern equine encephalitis virus chimeric vaccine candidate
SampleEilat virus/Eastern equine encephalitis virus chimera:
virus
SourceEilat virus
Methodsingle particle reconstruction / cryo EM / 11 Å resolution
AuthorsSherman MB / Erasmus JH / Frolov I / Weaver SC / Nasar F
CitationJournal: J. Virol. / Year: 2018
Title: Novel Insect-Specific Eilat Virus-Based Chimeric Vaccine Candidates Provide Durable, Mono- and Multivalent, Single-Dose Protection against Lethal Alphavirus Challenge.
Authors: Jesse H Erasmus / Robert L Seymour / Jason T Kaelber / Dal Y Kim / Grace Leal / Michael B Sherman / Ilya Frolov / Wah Chiu / Scott C Weaver / Farooq Nasar
Abstract: Most alphaviruses are mosquito borne and exhibit a broad host range, infecting many different vertebrates, including birds, rodents, equids, humans, and nonhuman primates. Recently, a ...Most alphaviruses are mosquito borne and exhibit a broad host range, infecting many different vertebrates, including birds, rodents, equids, humans, and nonhuman primates. Recently, a host-restricted, mosquito-borne alphavirus, Eilat virus (EILV), was described with an inability to infect vertebrate cells based on defective attachment and/or entry, as well as a lack of genomic RNA replication. We investigated the utilization of EILV recombinant technology as a vaccine platform against eastern (EEEV) and Venezuelan equine encephalitis viruses (VEEV), two important pathogens of humans and domesticated animals. EILV chimeras containing structural proteins of EEEV or VEEV were engineered and successfully rescued in cells. Cryo-electron microscopy reconstructions at 8 and 11 Å of EILV/VEEV and EILV/EEEV, respectively, showed virion and glycoprotein spike structures similar to those of VEEV-TC83 and other alphaviruses. The chimeras were unable to replicate in vertebrate cell lines or in brains of newborn mice when injected intracranially. Histopathologic examinations of the brain tissues showed no evidence of pathological lesions and were indistinguishable from those of mock-infected animals. A single-dose immunization of either monovalent or multivalent EILV chimera(s) generated neutralizing antibody responses and protected animals against lethal challenge 70 days later. Lastly, a single dose of monovalent EILV chimeras generated protective responses as early as day 1 postvaccination and partial or complete protection by day 6. These data demonstrate the safety, immunogenicity, and efficacy of novel insect-specific EILV-based chimeras as potential EEEV and VEEV vaccines. Mostly in the last decade, insect-specific viruses have been discovered in several arbovirus families. However, most of these viruses are not well studied and largely have been ignored. We explored the use of the mosquito-specific alphavirus EILV as an alphavirus vaccine platform in well-established disease models for eastern (EEE) and Venezuelan equine encephalitis (VEE). EILV-based chimeras replicated to high titers in a mosquito cell line yet retained their host range restriction in vertebrates both and In addition, the chimeras generated immune responses that were higher than those of other human and/or equine vaccines. These findings indicate the feasibility of producing a safe, efficacious, mono- or multivalent vaccine against the encephalitic alphaviruses VEEV and EEEV. Lastly, these data demonstrate how host-restricted, insect-specific viruses can be engineered to develop vaccines against related pathogenic arboviruses that cause severe disease in humans and domesticated animals.
DateDeposition: Aug 31, 2017 / Header (metadata) release: Sep 13, 2017 / Map release: Nov 22, 2017 / Last update: Jul 18, 2018

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Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 0.0045
  • Imaged by UCSF Chimera
  • Download
  • Surface view colored by radius
  • Surface level: 0.0045
  • Imaged by UCSF Chimera
  • Download
Movie viewer
Structure viewerEM map:
SurfViewMolmilJmol/JSmol
Supplemental images

Downloads & links

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Map

Fileemd_7004.map.gz (map file in CCP4 format, 364501 KB)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
450 pix
2.35 Å/pix.
= 1057.5 Å
450 pix
2.35 Å/pix.
= 1057.5 Å
450 pix
2.35 Å/pix.
= 1057.5 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 2.35 Å
Density
Contour Level:0.0045 (by author), 0.0045 (movie #1):
Minimum - Maximum-0.005502032 - 0.010450059
Average (Standard dev.)0.00027772094 (0.0010883694)
Details

EMDB XML:

Space Group Number1
Map Geometry
Axis orderXYZ
Dimensions450450450
Origin-225.-225.-225.
Limit224.224.224.
Spacing450450450
CellA=B=C: 1057.5 Å
α=β=γ: 90.0 deg.

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z2.352.352.35
M x/y/z450450450
origin x/y/z0.0000.0000.000
length x/y/z1057.5001057.5001057.500
α/β/γ90.00090.00090.000
start NX/NY/NZ
NX/NY/NZ
MAP C/R/S123
start NC/NR/NS-225-225-225
NC/NR/NS450450450
D min/max/mean-0.0060.0100.000

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Supplemental data

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Sample components

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Entire Eilat virus/Eastern equine encephalitis virus chimera

EntireName: Eilat virus/Eastern equine encephalitis virus chimera / Number of components: 1

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Component #1: virus, Eilat virus

VirusName: Eilat virus / Class: VIRION / Empty: No / Enveloped: Yes / Isolate: OTHER
MassTheoretical: 42 MDa
SpeciesSpecies: Eilat virus
Source (engineered)Expression System: Aedes albopictus (Asian tiger mosquito) / Cell of expression system: C7/10
Source (natural)Host Species: Aedes

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Experimental details

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Sample preparation

SpecimenSpecimen state: particle / Method: cryo EM
Sample solutionpH: 7.4
VitrificationCryogen name: ETHANE

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Electron microscopy imaging

ImagingMicroscope: JEOL 2200FS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Electron dose: 2 e/Å2 / Illumination mode: FLOOD BEAM
LensImaging mode: BRIGHT FIELD / Energy filter: In-column Omega Filter
Specimen HolderModel: GATAN LIQUID NITROGEN
CameraDetector: GATAN ULTRASCAN 4000 (4k x 4k)

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Image acquisition

Image acquisitionNumber of digital images: 126

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Image processing

ProcessingMethod: single particle reconstruction / Applied symmetry: I (icosahedral) / Number of projections: 2145
3D reconstructionAlgorithm: FOURIER SPACE / Resolution: 11 Å / Resolution method: FSC 0.5 CUT-OFF

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