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

• Published in: PloS one Vol. 14; no. 10; p. e0223684
• Main Authors: Kato, Hirofumi, Takayama-Ito, Mutsuyo, Iizuka-Shiota, Itoe, Fukushi, Shuetsu, Posadas-Herrera, Guillermo, Horiya, Madoka, Satoh, Masaaki, Yoshikawa, Tomoki, Yamada, Souichi, Harada, Shizuko, Fujii, Hikaru, Shibamura, Miho, Inagaki, Takuya, Morimoto, Kinjiro, Saijo, Masayuki, Lim, Chang-Kweng
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 07.10.2019; Public Library of Science (PLoS)
• Subjects: Amino acids; Animal experimentation; Animals; Antibodies; Antibodies, Neutralizing - immunology; Antibodies, Viral - immunology; Biology and life sciences; Cell Line, Tumor; Chlorocebus aethiops; Coronaviridae; Coronavirus Infections - prevention & control; Coronaviruses; Deoxyribonucleic acid; DNA; Domains; Ebola virus; Female; Fluorescent antibody technique; Genes; Genetic aspects; Genetics; Genomes; Glycoproteins; HEK293 Cells; Humans; Immunofluorescence; Immunogenicity; Immunogenicity, Vaccine; Infectious diseases; Lyssavirus; Medicine and Health Sciences; Mice; Mice, Inbred BALB C; Mice, Inbred ICR; Middle East respiratory syndrome; Middle East Respiratory Syndrome Coronavirus - immunology; Neutralizing; Novels; Pathogenicity; Pathogens; Prevention; Proteins; Rabies; Rabies virus - genetics; Rabies virus - physiology; Replication; Respiratory diseases; Risk factors; RNA polymerase; Safety and security measures; Severe acute respiratory syndrome; Signs and symptoms; Spike glycoprotein; Spike Glycoprotein, Coronavirus - immunology; Vaccines; Vaccines, Synthetic - genetics; Vaccines, Synthetic - immunology; Vero Cells; Viral Vaccines - genetics; Viral Vaccines - immunology; Virology; Virus Replication; Viruses; Middle East; Saudi Arabia; Japan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0223684

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.