Construction and Characterization of a Chimeric Viral Like Particle (VLP)-based Vaccine Candidate against Dengue Virus Serotype 2

Abstract

As a licensed live-attenuated vaccine for Dengue virus (DENV) currently indicates a necessity of improving the induction of protective immunity against diseases, especially dengue virus serotype 2 (DENV-2) infection. This study, therefore, aimed to develop a new chimeric virus-like particle (VLP) vaccine candidate against DENV-2 by using the woodchuck hepatitis virus core antigen (WHcAg) as a vaccine platform to expose the fusion loop and cooperating with the domain III of E protein of DENV-2 (as a prototype) on the particle surface, which was named WHcAg-FL-DIII DENV-2. As a control, the WHcAg (wild-type VLP) was also generated. Both of the chimeric WHcAg-FL-DIII DENV-2 vaccine candidate and the control could be expressed in Escherichia coli as soluble proteins, while electron microscopy showed the presence of VLP formations. Most of the produced proteins, however, are the inclusion bodies (IBs) which should be further solubilized into a monomeric form under appropriate extraction conditions and being reassembled by dialysis methods.

In conclusion, this research demonstrates that WHcAg-derived VLP can serve as a useful platform for the display of fusion loop-EDIII DENV-2. However, a further optimization of the protein purification process is required before evaluating its immunogenicity in vivo.