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A variant-proof SARS-CoV-2 vaccine targeting HR1 domain in S2 subunit of spike protein.
Pang, Wei; Lu, Ying; Zhao, Yan-Bo; Shen, Fan; Fan, Chang-Fa; Wang, Qian; He, Wen-Qiang; He, Xiao-Yan; Li, Ze-Kai; Chen, Tao-Tao; Yang, Cui-Xian; Li, You-Zhi; Xiao, Si-Xuan; Zhao, Zu-Jiang; Huang, Xu-Sheng; Luo, Rong-Hua; Yang, Liu-Meng; Zhang, Mi; Dong, Xing-Qi; Li, Ming-Hua; Feng, Xiao-Li; Zhou, Qing-Cui; Qu, Wang; Jiang, Shibo; Ouyang, Songying; Zheng, Yong-Tang.
  • Pang W; Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kun
  • Lu Y; University of the Chinese Academy of Sciences, Beijing, China.
  • Zhao YB; Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kun
  • Shen F; University of the Chinese Academy of Sciences, Beijing, China.
  • Fan CF; The Key Laboratory of Innate Immune Biology of Fujian Province, Provincial University Key Laboratory of Cellular Stress Response and Metabolic Regulation, Biomedical Research Center of South China, Key Laboratory of OptoElectronic Science and Technology for Medicine of Ministry of Education, College
  • Wang Q; Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kun
  • He WQ; University of the Chinese Academy of Sciences, Beijing, China.
  • He XY; Division of Animal Model Research, Institute for Laboratory Animal Resources, National Institutes for Food and Drug Control, Beijing, China.
  • Li ZK; Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, School of Basic Medical Sciences, Fudan University, Shanghai, China.
  • Chen TT; Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kun
  • Yang CX; University of the Chinese Academy of Sciences, Beijing, China.
  • Li YZ; Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kun
  • Xiao SX; University of the Chinese Academy of Sciences, Beijing, China.
  • Zhao ZJ; The Key Laboratory of Innate Immune Biology of Fujian Province, Provincial University Key Laboratory of Cellular Stress Response and Metabolic Regulation, Biomedical Research Center of South China, Key Laboratory of OptoElectronic Science and Technology for Medicine of Ministry of Education, College
  • Huang XS; The Key Laboratory of Innate Immune Biology of Fujian Province, Provincial University Key Laboratory of Cellular Stress Response and Metabolic Regulation, Biomedical Research Center of South China, Key Laboratory of OptoElectronic Science and Technology for Medicine of Ministry of Education, College
  • Luo RH; Yunnan Provincial Infectious Disease Hospital, Kunming, Yunnan, China.
  • Yang LM; The Key Laboratory of Innate Immune Biology of Fujian Province, Provincial University Key Laboratory of Cellular Stress Response and Metabolic Regulation, Biomedical Research Center of South China, Key Laboratory of OptoElectronic Science and Technology for Medicine of Ministry of Education, College
  • Zhang M; The Key Laboratory of Innate Immune Biology of Fujian Province, Provincial University Key Laboratory of Cellular Stress Response and Metabolic Regulation, Biomedical Research Center of South China, Key Laboratory of OptoElectronic Science and Technology for Medicine of Ministry of Education, College
  • Dong XQ; Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kun
  • Li MH; University of the Chinese Academy of Sciences, Beijing, China.
  • Feng XL; Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kun
  • Zhou QC; University of the Chinese Academy of Sciences, Beijing, China.
  • Qu W; Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kun
  • Jiang S; Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kun
  • Ouyang S; Yunnan Provincial Infectious Disease Hospital, Kunming, Yunnan, China.
  • Zheng YT; Yunnan Provincial Infectious Disease Hospital, Kunming, Yunnan, China.
Cell Res ; 32(12): 1068-1085, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-2117525
ABSTRACT
The emerging SARS-CoV-2 variants, commonly with many mutations in S1 subunit of spike (S) protein are weakening the efficacy of the current vaccines and antibody therapeutics. This calls for the variant-proof SARS-CoV-2 vaccines targeting the more conserved regions in S protein. Here, we designed a recombinant subunit vaccine, HR121, targeting the conserved HR1 domain in S2 subunit of S protein. HR121 consisting of HR1-linker1-HR2-linker2-HR1, is conformationally and functionally analogous to the HR1 domain present in the fusion intermediate conformation of S2 subunit. Immunization with HR121 in rabbits and rhesus macaques elicited highly potent cross-neutralizing antibodies against SARS-CoV-2 and its variants, particularly Omicron sublineages. Vaccination with HR121 achieved near-full protections against prototype SARS-CoV-2 infection in hACE2 transgenic mice, Syrian golden hamsters and rhesus macaques, and effective protection against Omicron BA.2 infection in Syrian golden hamsters. This study demonstrates that HR121 is a promising candidate of variant-proof SARS-CoV-2 vaccine with a novel conserved target in the S2 subunit for application against current and future SARS-CoV-2 variants.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 Vaccines / COVID-19 Type of study: Randomized controlled trials Topics: Vaccines / Variants Limits: Animals / Humans Language: English Journal: Cell Res Year: 2022 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 Vaccines / COVID-19 Type of study: Randomized controlled trials Topics: Vaccines / Variants Limits: Animals / Humans Language: English Journal: Cell Res Year: 2022 Document Type: Article