A novel rabies vaccine based on infectious propagating particles derived from hybrid VEEV-Rabies replicon.

EBioMedicine
Ya-Nan ZhangBo Zhang

Abstract

Live attenuated vaccines (LAVs) can mimic natural infection and have advantages to stimulate a robust and sustained immune response as well as to confer long-term protection. However, safety concerns is one of the major obstacles for LAVs development. In an effort to achieve the optimal balance between immunogenicity and safety, researchers currently have taken different strategies for the development of LAVs. We constructed a novel infectious self-propagating hybrid replicon particle (PRP), VEEV-RABV-G, through replacing the entire structural proteins of the Venezuelan equine encephalitis virus (VEEV) with the glycoprotein of rabies virus (RABV-G) as the single structural protein. We evaluated the potential of VEEV-RABV-G as a safe live attenuated vaccine in mice model. We found that VEEV-RABV-G could self-propagate efficiently in cell culture and induce a robust humoral immunity and provide protection against virulent RABV challenge in immunized mice. Remarkably, VEEV-RABV-G is highly attenuated in both adult and sucking mice, causing much weaker inflammatory and apoptotic effects in the brains of infected adult mice and significantly lower weight loss and morbidity compared with the commonly used RABV-derived LAVs. This stud...Continue Reading

Methods Mentioned

BETA
flow cytometry
in vitro transcription
electrophoresis
transfection
electron microscopy
Fluorescence
transmission electron microscopy

Software Mentioned

NIH Image J
GraphPad
GraphPad Prism
ImageJ

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