Dengue virus-like particles mimic the antigenic properties of the infectious dengue virus envelope

Abstract

BackgroundThe 4 dengue serotypes (DENV) are mosquito-borne pathogens that are associated with severe hemorrhagic disease. DENV particles have a lipid bilayer envelope that anchors two membrane glycoproteins prM and E. Two E-protein monomers form head-to-tail homodimers and three E-dimers align to form “rafts” that cover the viral surface. Some human antibodies that strongly neutralize DENV bind to quaternary structure epitopes displayed on E protein dimers or higher order structures forming the infectious virus. Expression of prM and E in cell culture leads to the formation of DENV virus-like particles (VLPs) which are smaller than wildtype virus particles and replication defective due to the absence of a viral genome. There is no data available that describes the antigenic landscape on the surface of flavivirus VLPs in comparison to the better studied infectious virion.MethodsA large panel of well characterized antibodies that recognize epitope of ranging complexity were used in biochemical analytics to obtain a comparative antigenic surface view of VLPs in respect to virus particles. DENV patient serum depletions were performed the show the potential of VLPs in serological diagnostics.ResultsVLPs were confirmed to be heterogeneous in size morphology and maturation state. Yet, we show that many highly conformational and quaternary structure-dependent antibody epitopes found on virus particles are efficiently displayed on DENV1–4 VLP surfaces as well. Additionally, DENV VLPs can efficiently be used as antigens to deplete DENV patient sera from serotype specific antibody populations.ConclusionsThis study aids in further understanding epitopic landscape of DENV VLPs and presents a comparative antigenic surface view of VLPs in respect to virus particles. We propose the use VLPs as a safe and practical alternative to infectious virus as a vaccine and diagnostic antigen.Electronic supplementary materialThe online version of this article (10.1186/s12985-018-0970-2) contains supplementary material, which is available to authorized users.

Human antibody response to Zika targets type-specific quaternary structure epitopes

“…Depletion was confirmed by a ZIKV E80-binding ELISA. Plasma were also depleted of all ZIKV binding Abs using ZIKV VLPs as previously described (83). ZIKV VLPs were provided by The Native Antigen Company and produced by transiently expressing ZIKV prM and E proteins in suspension culture-adapted HEK-293 cells.…”

Recent Progress on the Versatility of Virus-Like Particles

“…VLPs have become important tools in the biomedical field. VLPs are capable of self-assembly, they have a repetitive order and, because of the absence of a viral genome, VLPs can confer high immunogenicity and antigenicity [5]. VLPs are commonly 20~200 nm in diameter [12], which is close to the optimal diameter recognized by DCs and antigen-presenting cells (APCs).…”

“…VLPs are non-genetic multimeric nanoparticles formed through the self-assembly of one or more viral structural proteins in vivo or in vitro. Having no viral genetic material, VLPs therefore have no pathogenicity or infectivity [5]. In addition, because of their similar conformation to that of natural viral particles, VLPs can mimic the antigenic epitopes of the natural virus [6].…”

Mosquito Cell-Derived Japanese Encephalitis Virus-Like Particles Induce Specific Humoral and Cellular Immune Responses in Mice

“…Mosquito cell-derived dengue 2 VLPs produced from stable C6/36 cell clones have been characterized in immunogenicity [35]. However, an understanding of VLP structures requires a characterization in the presence of epitopes and an estimate of their resemblance to authentic virions [36][37][38][39][40]. Researchers have demonstrated the efficacy of baculovirus as a vector for gene delivery into mosquitoes [41].…”