tetano
Editor, Senior Moderator
Cell Rep
. 2022 Dec 1;111845.
doi: 10.1016/j.celrep.2022.111845. Online ahead of print.
Rational identification of potent and broad sarbecovirus-neutralizing antibody cocktails from SARS convalescents
Yunlong Cao[SUP] 1 [/SUP], Fanchong Jian[SUP] 2 [/SUP], Zhiying Zhang[SUP] 3 [/SUP], Ayijiang Yisimayi[SUP] 4 [/SUP], Xiaohua Hao[SUP] 5 [/SUP], Linlin Bao[SUP] 6 [/SUP], Fei Yuan[SUP] 7 [/SUP], Yuanling Yu[SUP] 8 [/SUP], Shuo Du[SUP] 3 [/SUP], Jing Wang[SUP] 4 [/SUP], Tianhe Xiao[SUP] 9 [/SUP], Weiliang Song[SUP] 4 [/SUP], Ying Zhang[SUP] 3 [/SUP], Pulan Liu[SUP] 3 [/SUP], Ran An[SUP] 8 [/SUP], Peng Wang[SUP] 8 [/SUP], Yao Wang[SUP] 8 [/SUP], Sijie Yang[SUP] 10 [/SUP], Xiao Niu[SUP] 2 [/SUP], Yuhang Zhang[SUP] 7 [/SUP], Qingqing Gu[SUP] 8 [/SUP], Fei Shao[SUP] 8 [/SUP], Yaling Hu[SUP] 11 [/SUP], Weidong Yin[SUP] 11 [/SUP], Aihua Zheng[SUP] 7 [/SUP], Youchun Wang[SUP] 12 [/SUP], Chuan Qin[SUP] 13 [/SUP], Ronghua Jin[SUP] 14 [/SUP], Junyu Xiao[SUP] 15 [/SUP], Xiaoliang Sunney Xie[SUP] 16 [/SUP]
Affiliations
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron sublineages have escaped most receptor-binding domain (RBD)-targeting therapeutic neutralizing antibodies (NAbs), which proves that previous NAb drug screening strategies are deficient against the fast-evolving SARS-CoV-2. Better broad NAb drug candidate selection methods are needed. Here, we describe a rational approach for identifying RBD-targeting broad SARS-CoV-2 NAb cocktails. Based on high-throughput epitope determination, we propose that broad NAb drugs should target non-immunodominant RBD epitopes to avoid herd-immunity-directed escape mutations. Also, their interacting antigen residues should focus on sarbecovirus conserved sites and associate with critical viral functions, making the antibody-escaping mutations less likely to appear. Following these criteria, a featured non-competing antibody cocktail, SA55+SA58, is identified from a large collection of broad sarbecovirus NAbs isolated from SARS-CoV-2-vaccinated SARS convalescents. SA55+SA58 potently neutralizes ACE2-utilizing sarbecoviruses, including circulating Omicron variants, and could serve as broad SARS-CoV-2 prophylactics to offer long-term protection, especially for individuals who are immunocompromised or with high-risk comorbidities.
Keywords: CP: Immunology; CP: Microbiology; SARS-CoV-2; antibody; broad-spectrum; cocktail; omicron; prophylactics; sarbecovirus.
. 2022 Dec 1;111845.
doi: 10.1016/j.celrep.2022.111845. Online ahead of print.
Rational identification of potent and broad sarbecovirus-neutralizing antibody cocktails from SARS convalescents
Yunlong Cao[SUP] 1 [/SUP], Fanchong Jian[SUP] 2 [/SUP], Zhiying Zhang[SUP] 3 [/SUP], Ayijiang Yisimayi[SUP] 4 [/SUP], Xiaohua Hao[SUP] 5 [/SUP], Linlin Bao[SUP] 6 [/SUP], Fei Yuan[SUP] 7 [/SUP], Yuanling Yu[SUP] 8 [/SUP], Shuo Du[SUP] 3 [/SUP], Jing Wang[SUP] 4 [/SUP], Tianhe Xiao[SUP] 9 [/SUP], Weiliang Song[SUP] 4 [/SUP], Ying Zhang[SUP] 3 [/SUP], Pulan Liu[SUP] 3 [/SUP], Ran An[SUP] 8 [/SUP], Peng Wang[SUP] 8 [/SUP], Yao Wang[SUP] 8 [/SUP], Sijie Yang[SUP] 10 [/SUP], Xiao Niu[SUP] 2 [/SUP], Yuhang Zhang[SUP] 7 [/SUP], Qingqing Gu[SUP] 8 [/SUP], Fei Shao[SUP] 8 [/SUP], Yaling Hu[SUP] 11 [/SUP], Weidong Yin[SUP] 11 [/SUP], Aihua Zheng[SUP] 7 [/SUP], Youchun Wang[SUP] 12 [/SUP], Chuan Qin[SUP] 13 [/SUP], Ronghua Jin[SUP] 14 [/SUP], Junyu Xiao[SUP] 15 [/SUP], Xiaoliang Sunney Xie[SUP] 16 [/SUP]
Affiliations
- PMID: 36493787
- DOI: 10.1016/j.celrep.2022.111845
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron sublineages have escaped most receptor-binding domain (RBD)-targeting therapeutic neutralizing antibodies (NAbs), which proves that previous NAb drug screening strategies are deficient against the fast-evolving SARS-CoV-2. Better broad NAb drug candidate selection methods are needed. Here, we describe a rational approach for identifying RBD-targeting broad SARS-CoV-2 NAb cocktails. Based on high-throughput epitope determination, we propose that broad NAb drugs should target non-immunodominant RBD epitopes to avoid herd-immunity-directed escape mutations. Also, their interacting antigen residues should focus on sarbecovirus conserved sites and associate with critical viral functions, making the antibody-escaping mutations less likely to appear. Following these criteria, a featured non-competing antibody cocktail, SA55+SA58, is identified from a large collection of broad sarbecovirus NAbs isolated from SARS-CoV-2-vaccinated SARS convalescents. SA55+SA58 potently neutralizes ACE2-utilizing sarbecoviruses, including circulating Omicron variants, and could serve as broad SARS-CoV-2 prophylactics to offer long-term protection, especially for individuals who are immunocompromised or with high-risk comorbidities.
Keywords: CP: Immunology; CP: Microbiology; SARS-CoV-2; antibody; broad-spectrum; cocktail; omicron; prophylactics; sarbecovirus.