Immunological properties reveal the monovalent and bivalent recombinant dengue virus-like particles as candidate vaccine for dengue

Abstract

We aimed to systematically analyze the immunological properties of monovalent and bivalent dengue virus-like particles (DENV VLPs) prepared in our study and provided basis for the development of DENV VLPs as a promising non-infectious candidate vaccine for dengue infection. The DENV-1/2 VLPs were prepared in the GAP promoter-based P. pastoris expression system using α-factor secretion signal. Groups of mice were immunized by monovalent and bivalent VLPs compared with inactivated virions and PBS. Then, the humoral immune response in mice were tested by ELISA, immunofluorescence and neutralization assay. ELISA and Enzyme linked immunospot assay were performed for investigating cytokines production after virus challenge in vivo and in vitro, respectively. Besides, the protection ability of VLPs was assessed by passive protection assay in suckling mice. The recombinant DENV-1/2 VLPs were successfully expressed with α-factor secretion signal. Sera of mice immunized with monovalent and bivalent VLPs elevated the specific antibodies level comparable to inactivated virions group. The monovalent and bivalent VLPs induced specific cellular immune response as confirmed by ELISPOT. The PRNT 50 titers of monovalent and bivalent VLPs sera against DENV-1/2 were different ranging from 16 to 64. Moreover, anti-monovalent and anti-bivalent DENV VLPs sera displayed protective capacity in survival rate and morbidity. Monovalent and bivalent VLPs showed attracting vaccine effect for dengue virus. The multivalent VLPs may be promising for preventing different types of dengue virus.