Development of a Broadly Accessible Venezuelan Equine Encephalitis Virus Replicon Particle Vaccine Platform.
Identifieur interne : 000C94 ( Main/Exploration ); précédent : 000C93; suivant : 000C95Development of a Broadly Accessible Venezuelan Equine Encephalitis Virus Replicon Particle Vaccine Platform.
Auteurs : Sudhakar Agnihothram [États-Unis] ; Vineet D. Menachery [États-Unis] ; Boyd L. Yount [États-Unis] ; Lisa C. Lindesmith [États-Unis] ; Trevor Scobey [États-Unis] ; Alan Whitmore [États-Unis] ; Alexandra Sch Fer [États-Unis] ; Mark T. Heise [États-Unis] ; Ralph S. Baric [États-Unis]Source :
- Journal of virology [ 1098-5514 ] ; 2018.
Descripteurs français
- KwdFr :
- Animaux, Anticorps antiviraux (immunologie), Anticorps antiviraux (sang), Cellules Vero, Encéphalomyélite équine du Vénézuéla (), Encéphalomyélite équine du Vénézuéla (immunologie), Encéphalomyélite équine du Vénézuéla (virologie), Femelle, Humains, Lignée cellulaire, Souris, Souris de lignée BALB C, Syndrome respiratoire aigu sévère (), Syndrome respiratoire aigu sévère (immunologie), Syndrome respiratoire aigu sévère (virologie), Vaccins antiviraux (immunologie), Vaccins atténués (immunologie), Vieillissement (immunologie), Virus de l'encéphalite équine du Venezuela (génétique), Virus de l'encéphalite équine du Venezuela (immunologie), Virus du SRAS (immunologie), Zoonoses (), Zoonoses (virologie).
- MESH :
- génétique : Virus de l'encéphalite équine du Venezuela.
- immunologie : Anticorps antiviraux, Encéphalomyélite équine du Vénézuéla, Syndrome respiratoire aigu sévère, Vaccins antiviraux, Vaccins atténués, Vieillissement, Virus de l'encéphalite équine du Venezuela, Virus du SRAS.
- sang : Anticorps antiviraux.
- virologie : Encéphalomyélite équine du Vénézuéla, Syndrome respiratoire aigu sévère, Zoonoses.
- Animaux, Cellules Vero, Encéphalomyélite équine du Vénézuéla, Femelle, Humains, Lignée cellulaire, Souris, Souris de lignée BALB C, Syndrome respiratoire aigu sévère, Zoonoses.
English descriptors
- KwdEn :
- Aging (immunology), Animals, Antibodies, Viral (blood), Antibodies, Viral (immunology), Cell Line, Chlorocebus aethiops, Encephalitis Virus, Venezuelan Equine (genetics), Encephalitis Virus, Venezuelan Equine (immunology), Encephalomyelitis, Venezuelan Equine (immunology), Encephalomyelitis, Venezuelan Equine (prevention & control), Encephalomyelitis, Venezuelan Equine (virology), Female, Humans, Mice, Mice, Inbred BALB C, SARS Virus (immunology), Severe Acute Respiratory Syndrome (immunology), Severe Acute Respiratory Syndrome (prevention & control), Severe Acute Respiratory Syndrome (virology), Vaccines, Attenuated (immunology), Vero Cells, Viral Vaccines (immunology), Zoonoses (prevention & control), Zoonoses (virology).
- MESH :
- chemical , blood : Antibodies, Viral.
- genetics : Encephalitis Virus, Venezuelan Equine.
- immunology : Aging, Antibodies, Viral, Encephalitis Virus, Venezuelan Equine, Encephalomyelitis, Venezuelan Equine, SARS Virus, Severe Acute Respiratory Syndrome, Vaccines, Attenuated, Viral Vaccines.
- prevention & control : Encephalomyelitis, Venezuelan Equine, Severe Acute Respiratory Syndrome, Zoonoses.
- virology : Encephalomyelitis, Venezuelan Equine, Severe Acute Respiratory Syndrome, Zoonoses.
- Animals, Cell Line, Chlorocebus aethiops, Female, Humans, Mice, Mice, Inbred BALB C, Vero Cells.
Abstract
Zoonotic viruses circulate as swarms in animal reservoirs and can emerge into human populations, causing epidemics that adversely affect public health. Portable, safe, and effective vaccine platforms are needed in the context of these outbreak and emergence situations. In this work, we report the generation and characterization of an alphavirus replicon vaccine platform based on a non-select agent, attenuated Venezuelan equine encephalitis (VEE) virus vaccine, strain 3526 (VRP 3526). Using both noroviruses and coronaviruses as model systems, we demonstrate the utility of the VRP 3526 platform in the generation of recombinant proteins, production of virus-like particles, and in vivo efficacy as a vaccine against emergent viruses. Importantly, packaging under biosafety level 2 (BSL2) conditions distinguishes VRP 3526 from previously reported alphavirus platforms and makes this approach accessible to the majority of laboratories around the world. In addition, improved outcomes in the vulnerable aged models as well as against heterologous challenge suggest improved efficacy compared to that of previously attenuated VRP approaches. Taking these results together, the VRP 3526 platform represents a safe and highly portable system that can be rapidly deployed under BSL2 conditions for generation of candidate vaccines against emerging microbial pathogens.IMPORTANCE While VEE virus replicon particles provide a robust, established platform for antigen expression and vaccination, its utility has been limited by the requirement for high-containment-level facilities for production and packaging. In this work, we utilize an attenuated vaccine strain capable of use at lower biocontainment level but retaining the capacity of the wild-type replicon particle. Importantly, the new replicon platform provides equal protection for aged mice and following heterologous challenge, which distinguishes it from other attenuated replicon platforms. Together, the new system represents a highly portable, safe system for use in the context of disease emergence.
DOI: 10.1128/JVI.00027-18
PubMed: 29540599
Affiliations:
- États-Unis
- Caroline du Nord
- Chapel Hill (Caroline du Nord)
- Université de Caroline du Nord à Chapel Hill
Links toward previous steps (curation, corpus...)
- to stream PubMed, to step Corpus: 000A18
- to stream PubMed, to step Curation: 000A18
- to stream PubMed, to step Checkpoint: 000A16
- to stream Ncbi, to step Merge: 002F16
- to stream Ncbi, to step Curation: 002F16
- to stream Ncbi, to step Checkpoint: 002F16
- to stream Main, to step Merge: 000C96
- to stream Main, to step Curation: 000C94
Le document en format XML
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<term>Animals</term>
<term>Antibodies, Viral (blood)</term>
<term>Antibodies, Viral (immunology)</term>
<term>Cell Line</term>
<term>Chlorocebus aethiops</term>
<term>Encephalitis Virus, Venezuelan Equine (genetics)</term>
<term>Encephalitis Virus, Venezuelan Equine (immunology)</term>
<term>Encephalomyelitis, Venezuelan Equine (immunology)</term>
<term>Encephalomyelitis, Venezuelan Equine (prevention & control)</term>
<term>Encephalomyelitis, Venezuelan Equine (virology)</term>
<term>Female</term>
<term>Humans</term>
<term>Mice</term>
<term>Mice, Inbred BALB C</term>
<term>SARS Virus (immunology)</term>
<term>Severe Acute Respiratory Syndrome (immunology)</term>
<term>Severe Acute Respiratory Syndrome (prevention & control)</term>
<term>Severe Acute Respiratory Syndrome (virology)</term>
<term>Vaccines, Attenuated (immunology)</term>
<term>Vero Cells</term>
<term>Viral Vaccines (immunology)</term>
<term>Zoonoses (prevention & control)</term>
<term>Zoonoses (virology)</term>
</keywords>
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<term>Anticorps antiviraux (immunologie)</term>
<term>Anticorps antiviraux (sang)</term>
<term>Cellules Vero</term>
<term>Encéphalomyélite équine du Vénézuéla ()</term>
<term>Encéphalomyélite équine du Vénézuéla (immunologie)</term>
<term>Encéphalomyélite équine du Vénézuéla (virologie)</term>
<term>Femelle</term>
<term>Humains</term>
<term>Lignée cellulaire</term>
<term>Souris</term>
<term>Souris de lignée BALB C</term>
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<term>Syndrome respiratoire aigu sévère (immunologie)</term>
<term>Syndrome respiratoire aigu sévère (virologie)</term>
<term>Vaccins antiviraux (immunologie)</term>
<term>Vaccins atténués (immunologie)</term>
<term>Vieillissement (immunologie)</term>
<term>Virus de l'encéphalite équine du Venezuela (génétique)</term>
<term>Virus de l'encéphalite équine du Venezuela (immunologie)</term>
<term>Virus du SRAS (immunologie)</term>
<term>Zoonoses ()</term>
<term>Zoonoses (virologie)</term>
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</keywords>
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<term>Encéphalomyélite équine du Vénézuéla</term>
<term>Syndrome respiratoire aigu sévère</term>
<term>Vaccins antiviraux</term>
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<term>Vieillissement</term>
<term>Virus de l'encéphalite équine du Venezuela</term>
<term>Virus du SRAS</term>
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<term>Antibodies, Viral</term>
<term>Encephalitis Virus, Venezuelan Equine</term>
<term>Encephalomyelitis, Venezuelan Equine</term>
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<term>Severe Acute Respiratory Syndrome</term>
<term>Vaccines, Attenuated</term>
<term>Viral Vaccines</term>
</keywords>
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<term>Severe Acute Respiratory Syndrome</term>
<term>Zoonoses</term>
</keywords>
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</keywords>
<keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Encéphalomyélite équine du Vénézuéla</term>
<term>Syndrome respiratoire aigu sévère</term>
<term>Zoonoses</term>
</keywords>
<keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Encephalomyelitis, Venezuelan Equine</term>
<term>Severe Acute Respiratory Syndrome</term>
<term>Zoonoses</term>
</keywords>
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<term>Cell Line</term>
<term>Chlorocebus aethiops</term>
<term>Female</term>
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<term>Mice</term>
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<term>Vero Cells</term>
</keywords>
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<term>Cellules Vero</term>
<term>Encéphalomyélite équine du Vénézuéla</term>
<term>Femelle</term>
<term>Humains</term>
<term>Lignée cellulaire</term>
<term>Souris</term>
<term>Souris de lignée BALB C</term>
<term>Syndrome respiratoire aigu sévère</term>
<term>Zoonoses</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">Zoonotic viruses circulate as swarms in animal reservoirs and can emerge into human populations, causing epidemics that adversely affect public health. Portable, safe, and effective vaccine platforms are needed in the context of these outbreak and emergence situations. In this work, we report the generation and characterization of an alphavirus replicon vaccine platform based on a non-select agent, attenuated Venezuelan equine encephalitis (VEE) virus vaccine, strain 3526 (VRP 3526). Using both noroviruses and coronaviruses as model systems, we demonstrate the utility of the VRP 3526 platform in the generation of recombinant proteins, production of virus-like particles, and <i>in vivo</i>
efficacy as a vaccine against emergent viruses. Importantly, packaging under biosafety level 2 (BSL2) conditions distinguishes VRP 3526 from previously reported alphavirus platforms and makes this approach accessible to the majority of laboratories around the world. In addition, improved outcomes in the vulnerable aged models as well as against heterologous challenge suggest improved efficacy compared to that of previously attenuated VRP approaches. Taking these results together, the VRP 3526 platform represents a safe and highly portable system that can be rapidly deployed under BSL2 conditions for generation of candidate vaccines against emerging microbial pathogens.<b>IMPORTANCE</b>
While VEE virus replicon particles provide a robust, established platform for antigen expression and vaccination, its utility has been limited by the requirement for high-containment-level facilities for production and packaging. In this work, we utilize an attenuated vaccine strain capable of use at lower biocontainment level but retaining the capacity of the wild-type replicon particle. Importantly, the new replicon platform provides equal protection for aged mice and following heterologous challenge, which distinguishes it from other attenuated replicon platforms. Together, the new system represents a highly portable, safe system for use in the context of disease emergence.</div>
</front>
</TEI>
<affiliations><list><country><li>États-Unis</li>
</country>
<region><li>Caroline du Nord</li>
</region>
<settlement><li>Chapel Hill (Caroline du Nord)</li>
</settlement>
<orgName><li>Université de Caroline du Nord à Chapel Hill</li>
</orgName>
</list>
<tree><country name="États-Unis"><region name="Caroline du Nord"><name sortKey="Agnihothram, Sudhakar" sort="Agnihothram, Sudhakar" uniqKey="Agnihothram S" first="Sudhakar" last="Agnihothram">Sudhakar Agnihothram</name>
</region>
<name sortKey="Baric, Ralph S" sort="Baric, Ralph S" uniqKey="Baric R" first="Ralph S" last="Baric">Ralph S. Baric</name>
<name sortKey="Heise, Mark T" sort="Heise, Mark T" uniqKey="Heise M" first="Mark T" last="Heise">Mark T. Heise</name>
<name sortKey="Lindesmith, Lisa C" sort="Lindesmith, Lisa C" uniqKey="Lindesmith L" first="Lisa C" last="Lindesmith">Lisa C. Lindesmith</name>
<name sortKey="Menachery, Vineet D" sort="Menachery, Vineet D" uniqKey="Menachery V" first="Vineet D" last="Menachery">Vineet D. Menachery</name>
<name sortKey="Sch Fer, Alexandra" sort="Sch Fer, Alexandra" uniqKey="Sch Fer A" first="Alexandra" last="Sch Fer">Alexandra Sch Fer</name>
<name sortKey="Scobey, Trevor" sort="Scobey, Trevor" uniqKey="Scobey T" first="Trevor" last="Scobey">Trevor Scobey</name>
<name sortKey="Whitmore, Alan" sort="Whitmore, Alan" uniqKey="Whitmore A" first="Alan" last="Whitmore">Alan Whitmore</name>
<name sortKey="Yount, Boyd L" sort="Yount, Boyd L" uniqKey="Yount B" first="Boyd L" last="Yount">Boyd L. Yount</name>
</country>
</tree>
</affiliations>
</record>
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