A cocktail containing two synergetic antibodies broadly neutralizes SARS-CoV-2 and its variants including Omicron BA.1 and BA.2

doi:10.1101/2022.04.26.489529

KMS > 免疫化学研究所

	A cocktail containing two synergetic antibodies broadly neutralizes SARS-CoV-2 and its variants including Omicron BA.1 and BA.2
	Zhang, X.1; Luo, F.2,3; Zhang, H.1; Guo, H.4,5; Zhou, J.1,6; Li, T.2,3; Chen, S.1,6; Song, S.2,3; Shen, M.7; Wu, Y.1; Gao, Y.5,8; Han, X.2,3; Wang, Y.2,3; Hu, C.2,3; Lu, Y.5; Wang, W.9 ; Wang, K.10; Tang, N.10; Jin, T.11; Yang, C.12; Cheng, G.12; Yang, H.5,8; Jin, A.2,3; Ji, X.4,9,13 ; Gong, R.1; Chiu, S.11; Huang, A.10
	2022-04-26
摘要	Neutralizing antibodies (NAbs) can prevent and treat infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, continuously emerging variants, such as Omicron, have significantly reduced the potency of most known NAbs. The selection of NAbs with broad neutralizing activities and the identification of conserved critical epitopes are still urgently needed. Here, we identified an extremely potent antibody (55A8) by single B-cell sorting from convalescent SARS-CoV-2-infected patients that recognized the receptor-binding domain (RBD) in the SARS-CoV-2 spike (S) protein. 55A8 could bind to wild-type SARS-CoV-2, Omicron BA.1 and Omicron BA.2 simultaneously with 58G6, a NAb previously identified by our group. Importantly, an antibody cocktail containing 55A8 and 58G6 (2-cocktail) showed synergetic neutralizing activity with a half-maximal inhibitory concentration (IC₅₀) in the picomolar range in vitro and prophylactic efficacy in hamsters challenged with Omicron (BA.1) through intranasal delivery at an extraordinarily low dosage (25 μg of each antibody daily) at 3 days post-infection. Structural analysis by cryo-electron microscopy (cryo-EM) revealed that 55A8 is a Class III NAb that recognizes a highly conserved epitope. It could block angiotensin-converting enzyme 2 (ACE2) binding to the RBD in the S protein trimer via steric hindrance. The epitopes in the RBD recognized by 55A8 and 58G6 were found to be different and complementary, which could explain the synergetic mechanism of these two NAbs. Our findings not only provide a potential antibody cocktail for clinical use against infection with current SARS-CoV-2 strains and future variants but also identify critical epitope information for the development of better antiviral agents.
语种	英语
DOI	10.1101/2022.04.26.489529
相关网址	查看原文
出处	bioRxiv
收录类别	PPRN.PPRN
WOS记录号	PPRN:9715882
WOS类目	Immunology
资助项目	Natural Science Foundation of Hubei Province of China["YDZX20213100001556","LG202101-01-07","2018YFA0507100","cstc2021jscx-fyzxX0001","2017ZX10202203","32170949","2019CFA076"] ; National Natural Science Foundation of China["81871639","2016YFD0500300","20XD1422900"] ; National Science and Technology[92169109] ; Science & Technology Commission of Chongqing[81871656] ; National Key Research and Development Program of China[8181101099]
文献类型	预印本
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/348537
专题	免疫化学研究所生命科学与技术学院_硕士生免疫化学研究所_公共科研平台_生物医学大数据平台
通讯作者	Yang, H.; Jin, A.; Ji, X.; Gong, R.; Chiu, S.; Huang, A.
作者单位	1.Wuhan Inst Virol, Chinese Acad Sci, CAS Key Lab Special Pathogens & Biosafety, Ctr Biosafety Mega Sci, Wuhan 430071, Hubei, Peoples R China 2.Chongqing Med Univ, Affiliated Hosp 2, Inst Viral Hepatitis, Dept Infect Dis, Chongqing 400010, Peoples R China 3.Univ Sci & Technol China, Div Life Sci & Med, Hefei 230026, Anhui, Peoples R China 4.Mindao Haoyue Co Ltd, SQ0042 Lanyuan Hall, 61 Daxuecheng Middle Rd, Chongqing 400042, Peoples R China 5.Minist Educ, Engn Res Ctr Prot & Peptide Med, Nanjing 210023, Peoples R China 6.Chongqing Med Univ, Coll Basic Med, Dept Immunol, Chongqing 400010, Peoples R China 7.Chongqing Med Univ, Chongqing Key Lab Basic & Translat Res Tumor Immunol, Chongqing 400010, Peoples R China 8.Nanjing Univ, Inst Viruses & Infect Dis, Inst Artificial Intelligence Biomed, Chem & Biomed Innovat Ctr ChemB, Nanjing 210023, Peoples R China 9.Shanghai Tech Univ, Shanghai Inst Adv Immunochem Studies, Sch Life Sci & Technol, Shanghai 201210, Peoples R China 10.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 11.First Affiliated Hosp Chongqing Med Univ, Dept Endocrine Breast Surg, Chongqing 400010, Peoples R China 12.Shanghai Clin Res & Trial Ctr, Shanghai 201210, Peoples R China 13.Chongqing Med Univ, Inst Life Sci, Chongqing 400010, Peoples R China
推荐引用方式 GB/T 7714	Zhang, X.,Luo, F.,Zhang, H.,et al. A cocktail containing two synergetic antibodies broadly neutralizes SARS-CoV-2 and its variants including Omicron BA.1 and BA.2. 2022.