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Development of a Broadly Accessible VEE Replicon Particle Vaccine Platform.

Development of a Broadly Accessible VEE Replicon Particle Vaccine Platform.
Author Information (click to view)

Agnihothram S, Menachery VD, Yount BL, Lindesmith LC, Scobey T, Whitmore A, Schäfer A, Heise MT, Baric RS,


Agnihothram S, Menachery VD, Yount BL, Lindesmith LC, Scobey T, Whitmore A, Schäfer A, Heise MT, Baric RS, (click to view)

Agnihothram S, Menachery VD, Yount BL, Lindesmith LC, Scobey T, Whitmore A, Schäfer A, Heise MT, Baric RS,

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Journal of virology 2018 03 14() pii JVI.00027-18
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 manuscript, 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 utility of the VRP 3526 platform in generation of recombinant proteins, production of virus like particles, andefficacy as a vaccine against emergent viruses. Importantly, packaging under BSL2 conditions distinguishes VRP 3526 from previously reported alphavirus platforms and makes this approach accessible to the majority of labs around the world. In addition, improved outcomes in the vulnerable aged models as well as against heterologous challenge suggest improved efficacy compared to previous attenuated VRP approaches. Taken 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.While VEE replicon particles provide a robust, established platform for antigen expression and vaccination, its utility has been limited by the requirement for high containment facilities for production and packaging. In this manuscript, we utilize an attenuated vaccine strain capable of use at lower biocontainment, 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.

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