Dataset Information

Current Understanding of the Molecular Basis of Venezuelan Equine Encephalitis Virus Pathogenesis and Vaccine Development.

ABSTRACT: Venezuelan equine encephalitis virus (VEEV) is an alphavirus in the family Togaviridae. VEEV is highly infectious in aerosol form and a known bio-warfare agent that can cause severe encephalitis in humans. Periodic outbreaks of VEEV occur predominantly in Central and South America. Increased interest in VEEV has resulted in a more thorough understanding of the pathogenesis of this disease. Inflammation plays a paradoxical role of antiviral response as well as development of lethal encephalitis through an interplay between the host and viral factors that dictate virus replication. VEEV has efficient replication machinery that adapts to overcome deleterious mutations in the viral genome or improve interactions with host factors. In the last few decades there has been ongoing development of various VEEV vaccine candidates addressing the shortcomings of the current investigational new drugs or approved vaccines. We review the current understanding of the molecular basis of VEEV pathogenesis and discuss various types of vaccine candidates.

SUBMITTER: Sharma A

PROVIDER: S-EPMC6410161 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Current Understanding of the Molecular Basis of Venezuelan Equine Encephalitis Virus Pathogenesis and Vaccine Development.

Sharma Anuj A Knollmann-Ritschel Barbara B

Viruses 20190218 2

Venezuelan equine encephalitis virus (VEEV) is an alphavirus in the family Togaviridae. VEEV is highly infectious in aerosol form and a known bio-warfare agent that can cause severe encephalitis in humans. Periodic outbreaks of VEEV occur predominantly in Central and South America. Increased interest in VEEV has resulted in a more thorough understanding of the pathogenesis of this disease. Inflammation plays a paradoxical role of antiviral response as well as development of lethal encephalitis t ...[more]

PMID: 30781656

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Project description: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.

Dataset Information

Current Understanding of the Molecular Basis of Venezuelan Equine Encephalitis Virus Pathogenesis and Vaccine Development.

Publications

Current Understanding of the Molecular Basis of Venezuelan Equine Encephalitis Virus Pathogenesis and Vaccine Development.

Similar Datasets

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