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
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
Externí odkaz: