Inactivated Wild-Type Zika Virus (strain PRVABC59)

Virus-like particles (VLPs) are empty particles composed only of viral proteins that can serve as safe and valuable tools for clinical prevention and treatment strategies. Here, researchers used a novel strategy based on a baculovirus expression system to produce Zika virus (ZIKV) VLPs and demonstrated their feasibility as vaccine candidates. Premembrane (prM) and envelope (E) proteins were co-expressed in insect cells and self-assembled into particles that resembled Zika virus. They found that ZIKV VLPs could be prepared quickly and easily in large quantities using this system. The studies showed that these VLPs had good immunogenicity in immunized mice, as they stimulated high levels of virus-neutralizing antibody titers, ZIKV-specific IgG titers, and strong memory T cell responses. Therefore, the baculovirus-based ZIKV VLP vaccine is a safe, effective, and economical anti-ZIKV vaccine candidate.

In this study, BALB/c mice were immunized via the i.m. route three times at 2-week intervals with VLPs or the control immunizations (i.e., the positive control involving purified inactivated ZIKV, the negative control involving vAc-hsp70-egfp-infected Sf9 cell lysates or the blank control involving PBS). Based on the grayscale of the bands in Western blot analysis, the ratios of the doses of E and prM proteins in PIV relative to the VLPs used to immunize mice were 1.11:1 and 1.21:1, respectively (Figure 1A). To demonstrate whether the antibodies induced by VLPs could neutralize live ZIKV, microneutralization assays were performed, and the geometric mean titer (GMT) of each group was calculated (Figure 1B). In VLP-immunized mice, the neutralization titer after the first immunization was significantly higher than that of the pre-immunization serum (week 0), and the antibody titer at week 6 (2 weeks after the second booster immunization) was similar to that at week 4 (2 weeks after the first booster immunization), indicating that the last immunization did not significantly further enhance the neutralization response. The neutralization titer induced by VLP was lower than that induced by inactivated ZIKV, but it was significantly different from the other two control groups.

Figure 1. Antibody responses elicited by ZIKV VLPs or control vaccinations. (Dai S, et al., 2018)

As shown in Figures 1C and 4D, with purified VLPs as the coating antigen, the serum-specific IgG level of mice immunized with ZIKV VLPs was significantly higher than that of the control mice. In addition, the IgG response induced by inactivated ZIKV (positive control) and vAc-hsp70-egfp-infected Sf9 cell lysate (negative control) was higher than that of PBS (blank control). From the perspective of the VLP assembly process, in addition to specific ZIKV antigens, there may be some other proteins that are packaged into or mixed with VLPs, such as host cell proteins or baculovirus proteins, which may enhance the immunogenicity of VLPs.