An Inactivated Recombinant Rabies Virus Displaying the Zika Virus prM-E Induces Protective Immunity Against Both Pathogens

Background: The global spread of Zika virus (ZIKV), which caused a pandemic associated with microcephaly and neuropathology in newborns and adults, prompted pursuit of a safe and effective vaccine. Methods: Rabies virus (RABV)-based ZIKV vaccines encoding prM-E protein of ZIKV were constructed with signal peptide or transmembrane (TM) domain replaced by corresponding region of RABV G gene. The recombinant viruses were characterized by confocal microscopy analysis, western blotting, immunogold electron microscopy and one-step growth curves. The immunogenicity of recombinant viruses mixed with a complex adjuvant of ISA 201 VG and poly(I:C) was tested in Balb/c mice. Results: Three recombinant viruses expressing ZIKV prM-E were constructed (named ZI-D, ZI-E and ZI-F). The change of signal peptide was not conducive to protein expression. TM replacement promoted the increase of protein expression. After immunization, the anti-ZIKV IgG antibody lasted for at least 10 weeks. The titer of neutralizing antibodies (NAbs) at week 6 against ZIKV and RABV were all above protective titer. Moreover, ZI-E could stimulate the proliferation of spleen lymphocytes and promoted the secretion of cytokines. It also promoted the production of central memory T cell (TCM) among CD4+/CD8+ T cells and stimulates B cell activation and maturation. Interpretation: These results indicate that ZI-E all could induce ZIKV-specific humoral and cellular immune responses, which have the potential to be developed into promising vaccines for protection against both ZIKV and RABV infections. Funding Statement: This study was funded in part by the National Key Research and Development Program of China (grant numbers 2016YFD0500400) and the Fundamental Research Funds for the Central Universities, JLU. Declaration of Interests: The authors declare that they have no competing interests. Ethics Approval Statement: The study was approved by the Animal Welfare and Ethics Committee of the Institute of Veterinary Medicine of the Military Academy of Sciences (Laboratory Animal Care and Use Committee Authorization permit number JSY-DW-2018-02).