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

Autoři: Hirofumi Kato aff001;  Mutsuyo Takayama-Ito aff001;  Itoe Iizuka-Shiota aff001;  Shuetsu Fukushi aff001;  Guillermo Posadas-Herrera aff001;  Madoka Horiya aff001;  Masaaki Satoh aff001;  Tomoki Yoshikawa aff001;  Souichi Yamada aff001;  Shizuko Harada aff001;  Hikaru Fujii aff001;  Miho Shibamura aff001;  Takuya Inagaki aff001;  Kinjiro Morimoto aff003;  Masayuki Saijo aff001;  Chang-Kweng Lim aff001
Působiště autorů: Department of Virology I, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan aff001;  Department of Life Science and Medical Bioscience, Waseda University, Shinjuku-ku, Tokyo, Japan aff002;  Department of Pharmacy, Yasuda Women’s University, Hiroshima, Hiroshima, Japan aff003
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article


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.

Klíčová slova:

Antibodies – Recombinant proteins – Recombinant vaccines – Vaccines – Viral vaccines – Coronaviruses – Vaccine development – Inoculation


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