Development of a recombinant replication-deficient rabies virus-based bivalent-vaccine against MERS-CoV and rabies virus and its humoral immunogenicity in mice
Autor: | Miho Shibamura, Mutsuyo Takayama-Ito, Itoe Iizuka-Shiota, Shizuko Harada, Souichi Yamada, Hikaru Fujii, Tomoki Yoshikawa, Chang Kweng Lim, Hirofumi Kato, Kinjiro Morimoto, Madoka Horiya, Takuya Inagaki, Masayuki Saijo, Masaaki Satoh, Guillermo Posadas-Herrera, Shuetsu Fukushi |
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Rok vydání: | 2019 |
Předmět: |
RNA viruses
0301 basic medicine Coronaviruses Physiology viruses Pathology and Laboratory Medicine Antibodies Viral Virus Replication medicine.disease_cause Biochemistry Mice Immunogenicity Vaccine Immune Physiology Chlorocebus aethiops Medicine and Health Sciences Public and Occupational Health Vaccines Mice Inbred BALB C Mice Inbred ICR Vaccines Synthetic Immune System Proteins Recombinant Vaccines Multidisciplinary medicine.diagnostic_test Viral Vaccine Immunogenicity General Medicine Vaccination and Immunization Recombinant Proteins Infectious Diseases Medical Microbiology Viral Pathogens Viruses Spike Glycoprotein Coronavirus Middle East Respiratory Syndrome Coronavirus Medicine Female Pathogens Antibody General Agricultural and Biological Sciences Coronavirus Infections Research Article Infectious Disease Control Science Immunology 030106 microbiology Biology Immunofluorescence Microbiology General Biochemistry Genetics and Molecular Biology Antibodies Virus Viral vector 03 medical and health sciences Inoculation Virology Cell Line Tumor Vaccine Development medicine Animals Humans Microbial Pathogens Vero Cells Biology and life sciences Rabies virus Organisms Proteins Viral Vaccines Antibodies Neutralizing HEK293 Cells 030104 developmental biology Viral replication biology.protein Preventive Medicine |
Zdroj: | PLoS ONE PLoS ONE, Vol 14, Iss 10, p e0223684 (2019) PLOS ONE |
ISSN: | 1932-6203 |
Popis: | 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. |
Databáze: | OpenAIRE |
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