tetano
Editor, Senior Moderator
Cell
. 2020 Jun 28;S0092-8674(20)30812-6.
doi: 10.1016/j.cell.2020.06.035. Online ahead of print.
A Universal Design of Betacoronavirus Vaccines Against COVID-19, MERS, and SARS
Lianpan Dai[SUP] 1 [/SUP], Tianyi Zheng[SUP] 2 [/SUP], Kun Xu[SUP] 3 [/SUP], Yuxuan Han[SUP] 4 [/SUP], Lili Xu[SUP] 5 [/SUP], Enqi Huang[SUP] 6 [/SUP], Yaling An[SUP] 7 [/SUP], Yingjie Cheng[SUP] 6 [/SUP], Shihua Li[SUP] 8 [/SUP], Mei Liu[SUP] 9 [/SUP], Mi Yang[SUP] 9 [/SUP], Yan Li[SUP] 8 [/SUP], Huijun Cheng[SUP] 7 [/SUP], Yuan Yuan[SUP] 8 [/SUP], Wei Zhang[SUP] 8 [/SUP], Changwen Ke[SUP] 10 [/SUP], Gary Wong[SUP] 11 [/SUP], Jianxun Qi[SUP] 12 [/SUP], Chuan Qin[SUP] 13 [/SUP], Jinghua Yan[SUP] 14 [/SUP], George F Gao[SUP] 15 [/SUP]
Affiliations
Abstract
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.
Keywords: COVID-19; MERS; MERS-CoV; SARS; SARS-CoV; SARS-CoV-2; betacoronavirus; coronavirus; receptor-binding domain (RBD); vaccine.
. 2020 Jun 28;S0092-8674(20)30812-6.
doi: 10.1016/j.cell.2020.06.035. Online ahead of print.
A Universal Design of Betacoronavirus Vaccines Against COVID-19, MERS, and SARS
Lianpan Dai[SUP] 1 [/SUP], Tianyi Zheng[SUP] 2 [/SUP], Kun Xu[SUP] 3 [/SUP], Yuxuan Han[SUP] 4 [/SUP], Lili Xu[SUP] 5 [/SUP], Enqi Huang[SUP] 6 [/SUP], Yaling An[SUP] 7 [/SUP], Yingjie Cheng[SUP] 6 [/SUP], Shihua Li[SUP] 8 [/SUP], Mei Liu[SUP] 9 [/SUP], Mi Yang[SUP] 9 [/SUP], Yan Li[SUP] 8 [/SUP], Huijun Cheng[SUP] 7 [/SUP], Yuan Yuan[SUP] 8 [/SUP], Wei Zhang[SUP] 8 [/SUP], Changwen Ke[SUP] 10 [/SUP], Gary Wong[SUP] 11 [/SUP], Jianxun Qi[SUP] 12 [/SUP], Chuan Qin[SUP] 13 [/SUP], Jinghua Yan[SUP] 14 [/SUP], George F Gao[SUP] 15 [/SUP]
Affiliations
- PMID: 32645327
- DOI: 10.1016/j.cell.2020.06.035
Abstract
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.
Keywords: COVID-19; MERS; MERS-CoV; SARS; SARS-CoV; SARS-CoV-2; betacoronavirus; coronavirus; receptor-binding domain (RBD); vaccine.