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10.1016/j.cell.2020.06.035

http://scihub22266oqcxt.onion/10.1016/j.cell.2020.06.035
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suck abstract from ncbi


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pmid32645327      Cell 2020 ; 182 (3): 722-733.e11
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  • A Universal Design of Betacoronavirus Vaccines against COVID-19, MERS, and SARS #MMPMID32645327
  • Dai L; Zheng T; Xu K; Han Y; Xu L; Huang E; An Y; Cheng Y; Li S; Liu M; Yang M; Li Y; Cheng H; Yuan Y; Zhang W; Ke C; Wong G; Qi J; Qin C; Yan J; Gao GF
  • Cell 2020[Aug]; 182 (3): 722-733.e11 PMID32645327show ga
  • Vaccines are urgently needed to control the ongoing pandemic COVID-19 and previously emerging MERS/SARS caused by coronavirus (CoV) infections. The CoV spike receptor-binding domain (RBD) is an attractive vaccine target but is undermined by limited immunogenicity. We describe a dimeric form of MERS-CoV RBD that overcomes this limitation. The RBD-dimer significantly increased neutralizing antibody (NAb) titers compared to conventional monomeric form and protected mice against MERS-CoV infection. Crystal structure showed RBD-dimer fully exposed dual receptor-binding motifs, the major target for NAbs. Structure-guided design further yielded a stable version of RBD-dimer as a tandem repeat single-chain (RBD-sc-dimer) which retained the vaccine potency. We generalized this strategy to design vaccines against COVID-19 and SARS, achieving 10- to 100-fold enhancement of NAb titers. RBD-sc-dimers in pilot scale production yielded high yields, supporting their scalability for further clinical development. The framework of immunogen design can be universally applied to other beta-CoV vaccines to counter emerging threats.
  • |*Universal Design[MESH]
  • |Angiotensin-Converting Enzyme 2[MESH]
  • |Animals[MESH]
  • |Antibodies, Neutralizing/immunology[MESH]
  • |Antibodies, Viral/immunology[MESH]
  • |Betacoronavirus/chemistry/*immunology[MESH]
  • |COVID-19[MESH]
  • |COVID-19 Vaccines[MESH]
  • |Cell Line, Tumor[MESH]
  • |Chlorocebus aethiops[MESH]
  • |Coronavirus Infections/*prevention & control/virology[MESH]
  • |HEK293 Cells[MESH]
  • |Humans[MESH]
  • |Mice[MESH]
  • |Mice, Inbred BALB C[MESH]
  • |Middle East Respiratory Syndrome Coronavirus/chemistry/*immunology[MESH]
  • |Pandemics/*prevention & control[MESH]
  • |Peptidyl-Dipeptidase A/genetics/metabolism[MESH]
  • |Pneumonia, Viral/*prevention & control/virology[MESH]
  • |Protein Binding[MESH]
  • |Protein Interaction Domains and Motifs/immunology[MESH]
  • |Receptors, Virus/metabolism[MESH]
  • |SARS-CoV-2[MESH]
  • |Severe acute respiratory syndrome-related coronavirus/chemistry/*immunology[MESH]
  • |Sf9 Cells[MESH]
  • |Specific Pathogen-Free Organisms[MESH]
  • |Spodoptera[MESH]
  • |Transfection[MESH]
  • |Vaccination/methods[MESH]
  • |Vero Cells[MESH]


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