Development of a recombinant replication-deficient rabies virus-based bivalent-vaccine against MERS-CoV and rabies virus and its humoral immunogenicity in mice

PLoS One. 2019 Oct 7;14(10):e0223684. doi: 10.1371/journal.pone.0223684. eCollection 2019.

Abstract

Middle East respiratory syndrome-coronavirus (MERS-CoV) is an emerging virus that causes severe disease with fatal outcomes; however, there are currently no approved vaccines or specific treatments against MERS-CoV. Here, we developed a novel bivalent vaccine against MERS-CoV and rabies virus (RV) using the replication-incompetent P-gene-deficient RV (RVΔP), which has been previously established as a promising and safe viral vector. MERS-CoV spike glycoprotein comprises S1 and S2 subunits, with the S1 subunit being a primary target of neutralizing antibodies. Recombinant RVΔP, which expresses S1 fused with transmembrane and cytoplasmic domains together with 14 amino acids from the ectodomains of the RV-glycoprotein (RV-G), was developed using a reverse genetics method and named RVΔP-MERS/S1. Following generation of RVΔP-MERS/S1 and RVΔP, our analysis revealed that they shared similar growth properties, with the expression of S1 in RVΔP-MERS/S1-infected cells confirmed by immunofluorescence and western blot, and the immunogenicity and pathogenicity evaluated using mouse infection experiments. We observed no rabies-associated signs or symptoms in mice inoculated with RVΔP-MERS/S1. Moreover, virus-specific neutralizing antibodies against both MERS-CoV and RV were induced in mice inoculated intraperitoneally with RVΔP-MERS/S1. These findings indicate that RVΔP-MERS/S1 is a promising and safe bivalent-vaccine candidate against both MERS-CoV and RV.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / immunology
  • Cell Line, Tumor
  • Chlorocebus aethiops
  • Coronavirus Infections / prevention & control*
  • Female
  • HEK293 Cells
  • Humans
  • Immunogenicity, Vaccine*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred ICR
  • Middle East Respiratory Syndrome Coronavirus / immunology*
  • Rabies virus / genetics*
  • Rabies virus / physiology
  • Spike Glycoprotein, Coronavirus / immunology
  • Vaccines, Synthetic / genetics
  • Vaccines, Synthetic / immunology*
  • Vero Cells
  • Viral Vaccines / genetics
  • Viral Vaccines / immunology*
  • Virus Replication*

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Spike Glycoprotein, Coronavirus
  • Vaccines, Synthetic
  • Viral Vaccines

Grant support

This research was supported by grants for Research on Emerging and Re- emerging Infectious Diseases from the Ministry of Health, Labour and Welfare of Japan (H30-Sinkogyousei-Shitei-10109700) and by grants for the Research Program on Emerging and Re-emerging Infectious Diseases from the Japan Agency for Medical Research and Development [http://www.amed.go.jp/] under Grant Numbers 18fk0108070j0101 and 18fk0108072j0001. The funders played no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.