Abstract

The newly emerged mosquito-borne Zika virus (ZIKV) strains pose a global challenge owing to its ability to cause microcephaly and neurological disorders. Several ZIKV vaccine candidates have been proposed, including inactivated and live attenuated virus vaccines, vector-based vaccines, DNA and RNA vaccines. These have been shown to be efficacious in preclinical studies in mice and nonhuman primates, but their use will potentially be a threat to immunocompromised individuals and pregnant women. Virus-like particles (VLPs) are empty particles composed merely of viral proteins, which can serve as a safe and valuable tool for clinical prevention and treatment strategies. In this study, we used a new strategy to produce ZIKV VLPs based on the baculovirus expression system and demonstrated the feasibility of their use as a vaccine candidate. The pre-membrane (prM) and envelope (E) proteins were co-expressed in insect cells and self-assembled into particles similar to ZIKV. We found that the ZIKV VLPs could be quickly and easily prepared in large quantities using this system. The VLPs were shown to have good immunogenicity in immunized mice, as they stimulated high levels of virus neutralizing antibody titers, ZIKV-specific IgG titers and potent memory T cell responses. Thus, the baculovirus-based ZIKV VLP vaccine is a safe, effective and economical vaccine candidate for use against ZIKV.

Highlights

  • Zika virus (ZIKV), first discovered in 1947 (Dick et al 1952), is a mosquito-borne flavivirus and has posed a great threat to public health over the past three decades (Lessler et al 2016)

  • We introduced a method to construct ZIKV Virus-like particles (VLPs) based on the baculovirus expression system

  • The DNA fragment encoding ZIKV prME was inserted into AcMNPV bacmid under the control of the polyhedrin promoter, which generated the recombinant bacmid AcprME (Fig. 1A)

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Summary

Introduction

Zika virus (ZIKV), first discovered in 1947 (Dick et al 1952), is a mosquito-borne flavivirus and has posed a great threat to public health over the past three decades (Lessler et al 2016). During infection of host cells, the viral genome is translated in the cytoplasm of host cells as a single open reading frame that is subsequently cleaved into three structural proteins (C, prM and E) and seven non-structural proteins by viral and host proteases (Heinz and Stiasny 2012). The new virions assemble in the endoplasmic reticulum (ER) and bud as non-infectious immature particles consisting of 60 trimeric spikes of E-prM heterodimers (Zhang et al 2003). They are transported through the exocytic pathway of host cell until they reach the transGolgi network (TGN). The newly synthesized virions are transported to the cell surface for exocytosis

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