A human cell-based SARS-CoV-2 vaccine elicits potent neutralizing antibody responses and protects mice from SARS-CoV-2 challenge
| Autor: | Haoran Peng, Cuisong Zhu, Kangli Cao, Yutang Li, Ziling Zhang, Xiangchuan He, Zhongtian Qi, Shu Song, Xiangwei Wang, Xiaoyan Zhang, Chenjian Gu, Chen Zhao, Lanlan Dong, Ping Zhao, Duoduo Li, Youhua Xie, Chenli Qiu, Zhengfan Jiang, Meilan Fu, Xiujing Hong, Longfei Ding, Jianqing Xu, Chenguang Wang |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
K562-S
Epidemiology viruses Antibodies Viral Animals Genetically Modified Mice Immunogenicity Vaccine Drug Discovery Pandemic Medicine Neutralizing antibody Mice Inbred ICR biology Vaccination virus diseases neutralizing antibody General Medicine Human cell protection Specific Pathogen-Free Organisms Infectious Diseases Spike Glycoprotein Coronavirus Female Angiotensin-Converting Enzyme 2 Research Article Primates 2019-20 coronavirus outbreak COVID-19 Vaccines Coronavirus disease 2019 (COVID-19) Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mouse model Immunology cell-based vaccines Microbiology Virology Animals Humans business.industry SARS-CoV-2 COVID-19 Antibodies Neutralizing Macaca mulatta non-human primate model Mice Inbred C57BL HEK293 Cells Vaccines Inactivated biology.protein Parasitology business K562 Cells |
| Zdroj: | Emerging Microbes & Infections article-version (VoR) Version of Record |
| ISSN: | 2222-1751 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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