Development of a Novel Virus-Like Particle Vaccine Platform That Mimics the Immature Form of Alphavirus

Clinical and Vaccine Immunology : CVI
Akane UrakamiWataru Akahata

Abstract

Virus-like particles (VLPs) are noninfectious multiprotein structures that are engineered to self-assemble from viral structural proteins. Here, we developed a novel VLP-based vaccine platform utilizing VLPs from the chikungunya virus. We identified two regions within the envelope protein, a structural component of chikungunya, where foreign antigens can be inserted without compromising VLP structure. Our VLP displays 480 copious copies of an inserted antigen on the VLP surface in a highly symmetric manner and is thus capable of inducing strong immune responses against any inserted antigen. Furthermore, by mimicking the structure of the immature form of the virus, we altered our VLP'sin vivodynamics and enhanced its immunogenicity. We used the circumsporozoite protein (CSP) of thePlasmodium falciparummalaria parasite as an antigen and demonstrated that our VLP-based vaccine elicits strong immune responses against CSP in animals. The sera from immunized monkeys protected mice from malaria infection. Likewise, mice vaccinated withP. yoeliiCSP-containing VLPs were protected from an infectious sporozoite challenge. Hence, our uniquely engineered VLP platform can serve as a blueprint for the development of vaccines against other pat...Continue Reading

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Aug 1, 2018·PLoS Neglected Tropical Diseases·Jing JinGraham Simmons
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Methods Mentioned

BETA
flow cytometry
enzyme-linked immunosorbent assay
ELISA
electron microscopy
PCR
reverse transcription-PCR
transfection
column chromatography
transmission electron microscopy
transgenic

Software Mentioned

MARCO
GeneArt
CTFFIND3
cellSens Dimension
LEGINON
Prism
jspr
MOTIONCORR
GraphPad
RELION

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