Versatile live attenuated SARS-CoV-2 vaccine platform applicable to variants induces protective immunity
Versatile live attenuated SARS-CoV-2 vaccine platform applicable to variants induces protective immunity
SUMMARY Live attenuated vaccines are generally highly effective. Here, we aimed to develop one against SARS-CoV-2, based on the identification of three types of temperature-sensitive (TS) strains with mutations in nonstructural proteins (nsp), impaired proliferation at 37-39°C, and the capacity to induce protective immunity in Syrian hamsters. To develop a live-attenuated vaccine, we generated a virus that combined all these TS-associated mutations (rTS-all), which showed a robust TS phenotype in vitro and high attenuation in vivo. The vaccine induced an effective cross-reactive immune response and protected hamsters against homologous or heterologous viral challenges. Importantly, rTS-all rarely reverted to the wild-type phenotype. By combining these mutations with an Omicron spike protein to construct a recombinant virus, protection against the Omicron strain was obtained. We show that immediate and effective live-attenuated vaccine candidates against SARS-CoV-2 variants may be developed using rTS-all as a backbone to incorporate the spike protein of the variants.
Komatsu Sayuri、Okamura Shinya、Torii Shiho、Ueno Shiori、Suzuki Hidehiko、Kamitani Wataru、Matsuura Yoshiharu、Takekawa Shiro、Ebina Hirotaka、Miyazato Paola、Yamanishi Koichi、Ono Chikako、Yoshida Akiho
Virus Vaccine Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Institute for Open and Transdisciplinary Research Initiatives, Osaka University||The Research Foundation for Microbial Diseases of Osaka UniversityVirus Vaccine Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Institute for Open and Transdisciplinary Research Initiatives, Osaka University||The Research Foundation for Microbial Diseases of Osaka UniversityLaboratory of Virus Control, Research Institute for Microbial Diseases, Osaka University||Laboratory of Virus Control, Center for Infectious Disease Education and Research, Osaka UniversityDepartment of Infectious Diseases and Host Defense, Gunma University Graduate School of MedicineVirus Vaccine Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Institute for Open and Transdisciplinary Research Initiatives, Osaka University||The Research Foundation for Microbial Diseases of Osaka UniversityDepartment of Infectious Diseases and Host Defense, Gunma University Graduate School of MedicineLaboratory of Virus Control, Research Institute for Microbial Diseases, Osaka University||Laboratory of Virus Control, Center for Infectious Disease Education and Research, Osaka UniversityThe Research Foundation for Microbial Diseases of Osaka UniversityVirus Vaccine Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Institute for Open and Transdisciplinary Research Initiatives, Osaka University||The Research Foundation for Microbial Diseases of Osaka University||Virus Vaccine Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Research institute for Microbial Diseases, Osaka UniversityVirus Vaccine Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Institute for Open and Transdisciplinary Research Initiatives, Osaka University||The Research Foundation for Microbial Diseases of Osaka UniversityThe Research Foundation for Microbial Diseases of Osaka UniversityLaboratory of Virus Control, Research Institute for Microbial Diseases, Osaka University||Laboratory of Virus Control, Center for Infectious Disease Education and Research, Osaka UniversityVirus Vaccine Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Institute for Open and Transdisciplinary Research Initiatives, Osaka University||The Research Foundation for Microbial Diseases of Osaka University
预防医学基础医学生物科学研究方法、生物科学研究技术
SARS-CoV-2live-attenuated vaccinetemperature-sensitivensp3nsp14nsp16vaccine platform
Komatsu Sayuri,Okamura Shinya,Torii Shiho,Ueno Shiori,Suzuki Hidehiko,Kamitani Wataru,Matsuura Yoshiharu,Takekawa Shiro,Ebina Hirotaka,Miyazato Paola,Yamanishi Koichi,Ono Chikako,Yoshida Akiho.Versatile live attenuated SARS-CoV-2 vaccine platform applicable to variants induces protective immunity[EB/OL].(2025-03-28)[2025-05-15].https://www.biorxiv.org/content/10.1101/2021.02.15.430863.点此复制
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