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A human cell-based SARS-CoV-2 vaccine elicits potent neutralizing antibody responses and protects mice from SARS-CoV-2 challenge.
He, Xiangchuan; Ding, Longfei; Cao, Kangli; Peng, Haoran; Gu, Chenjian; Li, Yutang; Li, Duoduo; Dong, Lanlan; Hong, Xiujing; Wang, Xiangwei; Fu, Meilan; Qiu, Chenli; Zhu, Cuisong; Zhang, Ziling; Song, Shu; Wang, Chenguang; Jiang, Zhengfan; Xie, Youhua; Qi, Zhongtian; Zhao, Chen; Zhao, Ping; Zhang, Xiaoyan; Xu, Jianqing.
  • He X; Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Fudan University, Shanghai, People's Republic of China.
  • Ding L; Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Fudan University, Shanghai, People's Republic of China.
  • Cao K; Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Fudan University, Shanghai, People's Republic of China.
  • Peng H; Department of Microbiology, Second Military Medical University, Shanghai, People's Republic of China.
  • Gu C; Department of Medical Microbiology and Parasitology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
  • Li Y; Department of Medical Microbiology and Parasitology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
  • Li D; Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Fudan University, Shanghai, People's Republic of China.
  • Dong L; Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Fudan University, Shanghai, People's Republic of China.
  • Hong X; Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Fudan University, Shanghai, People's Republic of China.
  • Wang X; Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Fudan University, Shanghai, People's Republic of China.
  • Fu M; Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Fudan University, Shanghai, People's Republic of China.
  • Qiu C; Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Fudan University, Shanghai, People's Republic of China.
  • Zhu C; Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Fudan University, Shanghai, People's Republic of China.
  • Zhang Z; Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Fudan University, Shanghai, People's Republic of China.
  • Song S; Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Fudan University, Shanghai, People's Republic of China.
  • Wang C; Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Fudan University, Shanghai, People's Republic of China.
  • Jiang Z; Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, School of Life Sciences & Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, People's Republic of China.
  • Xie Y; Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Fudan University, Shanghai, People's Republic of China.
  • Qi Z; Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, School of Life Sciences & Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, People's Republic of China.
  • Zhao C; Department of Medical Microbiology and Parasitology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
  • Zhao P; Department of Microbiology, Second Military Medical University, Shanghai, People's Republic of China.
  • Zhang X; Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Fudan University, Shanghai, People's Republic of China.
  • Xu J; Department of Microbiology, Second Military Medical University, Shanghai, People's Republic of China.
Emerg Microbes Infect ; 10(1): 1555-1573, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1324547
ABSTRACT
To curb the pandemic of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), multiple platforms have been employed toward a safe and highly effective vaccine. Here, we develop a novel cell-based vaccine candidate, namely K562-S, by utilizing human cell K562 as a cellular carrier to display Spike (S) protein of SARS-CoV-2 on the membrane. Analogous to the traditional inactivated vaccine, K562-S cells can be propagated to a large scale by culturing and completely lose their viability after exposure to X-ray irradiation or formalin. We in turn demonstrated high immunogenicity of formalin-inactivated K562-S vaccine in both mouse and non-human primates and its protective efficacy in mice. In mice, immunization with inactivated K562-S vaccines can elicit potent neutralizing antibody (nAb) responses persisting longer than 5 months. We consequently showed in a hACE2 mouse model of SARS-CoV-2 infection that a two-shot vaccination with adjuvanted K562-S rendered greater than 3 log reduction in viral lung load and concomitant ameliorated lung pathology. Of importance, the administration of the same regimen in non-human primates was able to induce a neutralizing antibody titer averaging three-fold higher relative to human convalescent serum. These results together support the promise of K562-based, S-protein-expressing vaccines as a novel vaccination approach against SARS-CoV-2. Importantly, with a powerful capacity to carry external genes for cell-based vectors, this platform could rapidly generate two- and multiple-valent vaccines by incorporating SARS-CoV-2 mutants, SARS-CoV, or MERS-CoV.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antibodies, Neutralizing / Immunogenicity, Vaccine / COVID-19 Vaccines / SARS-CoV-2 / COVID-19 / Antibodies, Viral Topics: Vaccines Limits: Animals / Female / Humans Language: English Journal: Emerg Microbes Infect Year: 2021 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antibodies, Neutralizing / Immunogenicity, Vaccine / COVID-19 Vaccines / SARS-CoV-2 / COVID-19 / Antibodies, Viral Topics: Vaccines Limits: Animals / Female / Humans Language: English Journal: Emerg Microbes Infect Year: 2021 Document Type: Article