Journal: 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.
Date
Deposition: Aug 31, 2017 / Header (metadata) release: Sep 13, 2017 / Map release: Nov 22, 2017 / Last update: Jul 18, 2018
-
Structure visualization
Movie
Surface view with section colored by density value
Electron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Electron dose: 2 e/Å2 / Illumination mode: FLOOD BEAM
Lens
Imaging mode: BRIGHT FIELD / Energy filter: In-column Omega Filter
Specimen Holder
Model: GATAN LIQUID NITROGEN
Camera
Detector: GATAN ULTRASCAN 4000 (4k x 4k)
-
Image acquisition
Image acquisition
Number of digital images: 126
-
Image processing
Processing
Method: single particle reconstruction / Applied symmetry: I (icosahedral) / Number of projections: 2145
3D reconstruction
Algorithm: FOURIER SPACE / Resolution: 11 Å / Resolution method: FSC 0.5 CUT-OFF
+
About Yorodumi
-
News
-
Jul 12, 2017. Major update of PDB
Major update of PDB
wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary. This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated. See below links for details.
In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software). Now, EM Navigator and Yorodumi are based on the updated data.
Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
Related info.: EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi
Movie
Controller
EM Navigator
Omokage search
Yorodumi
Open data
Loading...
Basic information
Map data
Sample
Authors
Citation
Structure visualization
Movie viewer
Downloads & links
emd_7004.png (229.8 KB)
Links
Z (Sec.)
Y (Row.)
X (Col.)
Sample components
Electron microscopy imaging
Image processing