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The global spread of Zika virus (ZIKV), which caused a pandemic associated with Congenital Zika Syndrome and neuropathology in newborns and adults, prompted the pursuit of a safe and effective vaccine. Here, three kinds of recombinant rabies virus (RABV) encoding the prM-E protein of ZIKV were constructed: ZI-D (prM-E), ZI-E (transmembrane domain (TM) of prM-E replaced with RABV G) and ZI-F (signal peptide and TM domain of prM-E replaced with the region of RABV G). When the TM of prM-E was replaced with the region of RABV G (termed ZI-E), it promoted ZIKV E protein localization on the cell membrane and assembly on recombinant viruses. In addition, the change in the signal peptide with RABV G (termed ZI-F) was not conducive to foreign protein expression. The immunogenicity of recombinant viruses mixed with a complex adjuvant of ISA 201 VG and poly(I:C) was tested in BALB/c mice. After immunization with ZI-E, the anti-ZIKV IgG antibody lasted for at least 10 weeks. The titers of neutralizing antibodies (NAbs) against ZIKV and RABV at week 6 were all greater than the protective titers. Moreover, ZI-E stimulated the proliferation of splenic lymphocytes and promoted the secretion of cytokines. It also promoted the production of central memory T cells (TCMs) among CD4+/CD8+ T cells and stimulated B cell activation and maturation. These results indicate that ZI-E could induce ZIKV-specific humoral and cellular immune responses, which have the potential to be developed into a promising vaccine for protection against both ZIKV and RABV infections.

No abstract

Rabies is a fatal neurological zoonotic disease caused by the rabies virus (RABV), and the approved post‐exposure prophylaxis (PEP) procedure remains unavailable in areas with inadequate medical systems. Although strategies have been proposed for PEP and postinfection treatment (PIT), because of the complexity of the treatment procedures and the limited curative outcome, developing an effective treatment strategy remains a holy grail in rabies research. Herein, a facile approach is proposed involving photothermal therapy (PTT) and photothermally triggered immunological effects to realize effective PEP and PIT simultaneously. The designed photothermal agent (N+TT‐mCB nanoparticles) featured positively charged functional groups and high photo‐to‐heat efficiency, which are favorable for virus targeting and inactivation. The level of the virus at the site of infection in mice is significantly decreased upon treatment with orthotopic PTT, and the transfer of the virus to the brain is significantly inhibited. Furthermore, the survival ratio of the mice three days postinfection is increased by intracranial injection of N+TT‐mCB and laser irradiation. Overall, this work provides a platform for the effective treatment of RABV and opens a new avenue for future antiviral studies.

The emergence of Zika virus (ZIKV) infection, which is 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 in vaccines. In this study, we developed a bacterium‐like particle vaccine, ZI‐△‐PA‐GEM, based on the GEM‐PA system. The fusion protein ZI‐△‐PA, which contains the prM‐E‐△TM 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 to form ZI‐△‐PA‐GEM. Moreover, the intramuscular immunization of BALB/c mice with ZI‐△‐PA‐GEM combined with ISA 201 VG and poly(I:C) adjuvants induced durable ZIKV‐specific IgG and protective neutralizing antibody responses. Potent B‐cell/DC activation was also stimulated early after immunization. Notable, splenocyte proliferation, the secretion of multiple cytokines, T/B‐cell activation and central memory T‐cell responses were elicited. These data indicate that ZI‐△‐PA‐GEM is a promising bacterium‐like particle vaccine candidate for ZIKV.