Recent Advances in the Development of Virus-Like Particle-Based Flavivirus Vaccines

Abstract

Flaviviruses include several medically important viruses, such as Zika virus (ZIKV), Dengue virus (DENV), West Nile virus (WNV) and Japanese encephalitis virus (JEV). They have expanded in geographic distribution and refocused international attention in recent years. Vaccination is one of the most effective public health strategies for combating flavivirus infections. In this review, we summarized virus-like particle (VLP)-based vaccines against the above four mentioned flaviviruses. Potential strategies to improve the efficacy of VLP-based flavivirus vaccines were also illustrated. The applications of flavivirus VLPs as tools for viral detection and antiviral drug screening were finally proposed.

Keywords: Dengue virus; Japanese encephalitis virus; West Nile virus; Zika virus; flaviviruses; vaccines; virus-like particles.

Figure 1

Schematic model of a flavivirus particle. (A) Immature flavivirus particles. The surface of immature particles consists of 60 trimeric spikes and each spike is composed of a prM-E heterodimer. (B) Mature flavivirus particles. Mature particles are formed after prM cleavage and each particle contains 90 E homodimers and 90 M homodimers. The E glycoproteins are involved in receptor binding, attachment and virus-cell fusion.

Figure 2

The flavivirus life cycle. A flavivirus attaches to the cell through its binding to a receptor on cell surface of a host cell and subsequently enters the cell by receptor-mediated endocytosis. The low pH environment in the endosome triggers conformational changes of E protein, resulting in the fusion between viral and endosomal membranes and release of the viral genome into the cytoplasm for replication. The immature viral and subviral particles are assembled on the surface of the endoplasmic reticulum (ER), transported through the trans-Golgi network (TGN), and then cleaved by the host protease furin, resulting in the formation of mature viral particles, which are subsequently released by exocytosis.