An inactivated recombinant rabies virus displaying the Zika virus prM-E induces protective immunity against both pathogens

Abstract

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.

Research Advances on the Interactions between Rabies Virus Structural Proteins and Host Target Cells: Accrued Knowledge from the Application of Reverse Genetics Systems

“…induced VNA against RABV and ZIKV and induced a specific cellular immune response, with the potential to prevent ZIKV and RABV infection. [107].…”

“…Therefore, rLBNSE-Gn may be a promising bivalent vaccine candidate for the prevention of SFTS and rabies. Jin et al [107] obtained a recombinant RABV-expressing Zika virus (ZIKV)-prM-E and evaluated the immunogenicity in BALB/C mice. The recombinant virus induced VNA against RABV and ZIKV and induced a specific cellular immune response, with the potential to prevent ZIKV and RABV infection.…”

A recombinant rabies virus chimera expressing the DC-targeting molecular MAB2560 shows enhanced vaccine immunogenicity through activation of dendritic cells

“…The fragment was then inserted into the pCDNA3.0-CVS11 plasmid using the BsiW I and Sac II restriction sites, to construct the plasmid pCDNA3.0-CVS11-SP-MAB2560-TMCD. The recombinant pCDNA3.0-CVS11-SP-MAB2560-TMCD and pCDNA3.0-CVS11 plasmids were co-transfected into BSR cells with the helper plasmids to rescue the recombinant rCVS11-MAB2560 and rCVS11 viruses [ 33 , 34 ]. Briefly, BSR cells were seeded into 6-well plate (3×10 5 /mL) and were transfected with the recombinant plasmids (2.5μg), the helper plasmids pD-N (0.625μg), pD-P (0.3125μg), pD-L (0.125μg), and pD-G (0.1875μg).…”

“…The recombinant rCVS11-MAB2560 and rCVS11 viruses were inoculated separately into NA cells or BSR cells at MOI = 1 or 0.1. The supernatants were collected every 24 h. Virus titer was determined using the Reed-Muench method as described previously [ 34 ]. The neural tropism of the recombinant viruses was calculated by comparing the titers of rCVS11-MAB2560 or rCVS11 in NA cells (a kind of neurogenic cells) to those of in BSR cells (non-neurogenic cells) and represented as the ratio index.…”

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

“…To date, no accepted therapies or vaccines are available for ZIKV, and the WHO has made ZIKV vaccine development a top priority (Lin et al, 2018). Although substantial progress has been made toward the development of ZIKV vaccines, which are essential to control the spread of ZIKV, new vaccine search efforts are needed because of the complexity of ZIKV immunity and pathogenesis (Barba-Spaeth et al, 2016;Cugola et al, 2016;Jin et al, 2021). Neutralizing antibody epitopes exist on the surface of the ZIKV E protein (Dai et al, 2016;Li et al, 2008), and precursor membrane e2517 (prM) protein complexes with the E protein are usually ideal candidates for vaccine development.…”