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Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Cell 2020 ; 182 (3): 722-733.e11 Nephropedia Template TP
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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.