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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; 14(10):e0223684.Plos

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.

Authors+Show Affiliations

Department of Virology I, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan.Department of Virology I, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan.Department of Virology I, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan.Department of Virology I, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan.Department of Virology I, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan.Department of Virology I, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan.Department of Virology I, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan.Department of Virology I, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan.Department of Virology I, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan.Department of Virology I, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan.Department of Virology I, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan.Department of Virology I, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan.Department of Virology I, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan. Department of Life Science and Medical Bioscience, Waseda University, Shinjuku-ku, Tokyo, Japan.Department of Pharmacy, Yasuda Women's University, Hiroshima, Hiroshima, Japan.Department of Virology I, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan.Department of Virology I, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31589656

Citation

Kato, Hirofumi, et al. "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, vol. 14, no. 10, 2019, pp. e0223684.
Kato H, Takayama-Ito M, Iizuka-Shiota I, et al. 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;14(10):e0223684.
Kato, H., Takayama-Ito, M., Iizuka-Shiota, I., Fukushi, S., Posadas-Herrera, G., Horiya, M., Satoh, M., Yoshikawa, T., Yamada, S., Harada, S., Fujii, H., Shibamura, M., Inagaki, T., Morimoto, K., Saijo, M., & Lim, C. K. (2019). 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, 14(10), e0223684. https://doi.org/10.1371/journal.pone.0223684
Kato H, et al. 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;14(10):e0223684. PubMed PMID: 31589656.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Development of a recombinant replication-deficient rabies virus-based bivalent-vaccine against MERS-CoV and rabies virus and its humoral immunogenicity in mice. AU - Kato,Hirofumi, AU - Takayama-Ito,Mutsuyo, AU - Iizuka-Shiota,Itoe, AU - Fukushi,Shuetsu, AU - Posadas-Herrera,Guillermo, AU - Horiya,Madoka, AU - Satoh,Masaaki, AU - Yoshikawa,Tomoki, AU - Yamada,Souichi, AU - Harada,Shizuko, AU - Fujii,Hikaru, AU - Shibamura,Miho, AU - Inagaki,Takuya, AU - Morimoto,Kinjiro, AU - Saijo,Masayuki, AU - Lim,Chang-Kweng, Y1 - 2019/10/07/ PY - 2019/06/22/received PY - 2019/09/25/accepted PY - 2019/10/8/entrez PY - 2019/10/8/pubmed PY - 2020/3/11/medline SP - e0223684 EP - e0223684 JF - PloS one JO - PLoS One VL - 14 IS - 10 N2 - 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. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/31589656/Development_of_a_recombinant_replication_deficient_rabies_virus_based_bivalent_vaccine_against_MERS_CoV_and_rabies_virus_and_its_humoral_immunogenicity_in_mice_ L2 - https://dx.plos.org/10.1371/journal.pone.0223684 DB - PRIME DP - Unbound Medicine ER -