A bacterium-like particle vaccine displaying Zika virus prM-E induces systemic immune responses in mice

Abstract

AbstractThe emergence of Zika virus (ZIKV) infection, which is an unexpectedly associated with congenital defects, has prompted the development of safe and effective vaccines. The gram-positive enhancer matrix-protein anchor (GEM-PA) display system has emerged as a versatile and highly effective platform for delivering target proteins for vaccines. In this article, we developed a bacterium-like particle vaccine ZI-Δ-PA-GEM based on the GEM-PA system. The fusion protein ZI-Δ-PA, which contains the prM-E-Δ protein of ZIKV (with a stem-transmembrane region deletion) and the protein anchor PA3, was expressed. The fusion protein was successfully displayed on the GEM surface, forming ZI-Δ-PA-GEM. Moreover, when BALB/c mice were immunized intramuscularly with ZI-Δ-PA-GEM combined with 201 VG and poly(I:C) adjuvants, durable ZIKV-specific IgG and protective neutralizing antibody responses were induced. Potent B cell/DC activation was also be stimulated early after immunization. Remarkably, splenocyte proliferation, the secretion of multiple cytokines, T/B cell activation and central memory T cell responses were elicited. These data indicate that ZI-Δ-PA-GEM is a promising bacterium-like particle vaccine candidate for ZIKV.Author summaryBecause Zika virus (ZIKV) infection is considered as an example of “disease X”, the development of a safe and effective ZIKV vaccine is essential. The gram-positive enhancer matrix-protein anchor (GEM-PA) display system has been used in many vaccine studies due to its advantages. In this study, prM-E-△ protein of ZIKV (with a stem-transmembrane region deletion) and the protein anchor PA3 was fusion expressed, termed ZI-△-PA. Then the fusion protein ZI-△-PA could be displayed on the surface of GEM, forming ZI-△-PA-GEM. The author evaluated the immunogenicity of ZI-△-PA-GEM with the 201 VG and poly(I:C) adjuvants. The study demonstrates that ZI-△-PA-GEM induced mice to produce neutralizing antibody and specific cellular immune responses. The author believe that the bacterium-like particle vaccine ZI-△-PA-GEM has the potential to be used as the ZIKV vaccine.