A Recombinant Vesicular Stomatitis Virus Expressing the Junin Virus Glycoprotein for Arenavirus Countermeasure Development

Date
2019-12-01T06:00:00.000Z
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Abstract

Arenaviruses are pathogens of biodefense importance due to their potential for aerosol transmission and mortality rates reaching 30%. Here, we evaluated the use of a recombinant vesicular stomatitis virus expressing the Junin virus glycoprotein (rVSVΔG-JUNVGP) for the development of countermeasures against arenaviruses. First, we evaluated rVSVΔG-JUNVGP as a vaccine against lethal Junin virus (JUNV) challenge in a guinea pig model. Currently, there are no JUNV vaccines licensed by the United States Food and Drug Administration (FDA) for at-risk individuals. We demonstrated that rVSVΔG-JUNVGP generated 100% protective efficacy against lethal JUNV challenge using a single vaccine injection. We also showed that rVSVΔG-JUNVGP induced robust, high avidity IgG antibody titers as well as detectable neutralizing antibodies. We next evaluated the use of rVSVΔG-JUNVGP as a tool for the detection of JUNV neutralizing antibodies. Conventional methodologies for the detection and quantification of JUNV neutralizing antibodies have several limitations, including the length of time necessary to obtain results (6-8 days) and the requirement of a high containment (BSL-3/4) laboratory. In this study, we showed that rVSVΔG-JUNVGP could overcome these limitations, detecting neutralizing antibodies with the same sensitivity as currently available methods, but more rapidly (within 48 hours) and without the need for a high containment laboratory. Lastly, for biodefense and public health purposes the development of a cross protective arenavirus vaccine may be an important long-term research objective. We therefore developed a panel of chimeric glycoproteins which simultaneously express immunogenic epitopes from multiple arenavirus pathogens. We demonstrated that all chimeric GPs were adequately processed intracellularly, packaged into a rVSVΔG-GFP virion from the plasma membrane, and capable of cellular entry. Our findings suggest that these chimeric GPs may be good candidates to move forward into a rVSV vaccine vector for evaluation of protective efficacy in-vivo. Overall, the findings in these studies demonstrate that a rVSV vector system can be utilized to successfully advance arenavirus and JUNV-specific countermeasure development.

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Biology, Microbiology, Biology, Virology, Biology, Molecular
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