Characterization of Zika virus-like particles as potential vaccine antigens

Abstract

Background: Many of emerging and re-emerging epidemics are caused by viruses belonging to the Flaviviridae family. The family includes, among others, Dengue virus (DENV), West Nile virus, tick-borne encephalitis virus (TBEV) and Zika virus (ZIKV). ZIKV is a mosquito-transmitted flavivirus, which was found to be related to several diseases including infant microcephaly, Guillain-Barre Syndrome and some other neurological defects. In recent years ZIKV has spread throughout Asia, Africa and America and it co-circulates with other flaviviruses. Several laboratories have reported possible antibody-dependent enhancement of DENV infection after previous ZIKV infection. Therefore, the rational approach to the development of an effective vaccine is highly recommended. Currently, many types of potential vaccines are being tested: live-attenuated and inactivated viruses, viral vectors carrying ZIKV genes, viral DNA, mRNA and protein subunits, and virus-like particles (VLPs). This last option–VLPs, are characterized by lack of genetic material, which makes them non-infectious. ZIKV VLPs, similarly to most of other flaviviruses, are composed of viral proteins (prM/M and E), organized almost identically to the native virions. VLPs can be produced in different expression system: insect, mammalian and yeast cells. However, these systems differ in terms of culturing conditions, production efficiency, and post-translational modifications of protein. Methods and materials: Therefore, the main aim of the study was to evaluate ZIKV VLPs produced in two different expression systems, insect and mammalian cells, as vaccine antigens. Production of VLPs was monitored by Western blotting, dynamic light scattering (DLS), sucrose gradient sedimentation as well as by electron microscopy. Functional and conformational analysis of obtained VLPs was performed by enzyme-linked immunosorbent assay (ELISA) using a panel of conformational antibodies. Comparative analysis of immunological properties was performed using mouse model. Results: VLPs in two expression systems were successfully produced. Our study suggests that VLPs produced in various expression systems may differ in protein composition and conformation. All examined ZIKV VLPs were immunogenic as assayed by ELISA but varied greatly in virus neutralization efficacy. Conclusion: Our studies have confirm that ZIKV VLPs offer a promising approach for effective vaccination, even though the expression system greatly influences the antigenic and immunogenic properties.