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

PLoS Negl Trop Dis. 2021 Jun 4;15(6):e0009484. doi: 10.1371/journal.pntd.0009484. eCollection 2021 Jun.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Viral / immunology
  • Female
  • Humans
  • Immunity, Cellular
  • Mice
  • Mice, Inbred BALB C
  • Rabies / immunology
  • Rabies / prevention & control*
  • Rabies / virology
  • Rabies virus / genetics*
  • Rabies virus / immunology
  • T-Lymphocytes / immunology
  • Vaccines, Attenuated / administration & dosage
  • Vaccines, Attenuated / genetics
  • Vaccines, Attenuated / immunology
  • Viral Envelope Proteins / administration & dosage
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / immunology*
  • Viral Vaccines / administration & dosage
  • Viral Vaccines / genetics
  • Viral Vaccines / immunology*
  • Zika Virus / genetics
  • Zika Virus / immunology*
  • Zika Virus Infection / immunology
  • Zika Virus Infection / prevention & control*
  • Zika Virus Infection / virology

Substances

  • Antibodies, Viral
  • Vaccines, Attenuated
  • Viral Envelope Proteins
  • Viral Vaccines
  • prM protein, Flavivirus

Grants and funding

HLW was supported by “the Fundamental Research Funds for the Central Universities (2132020KJC016)”. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.