Neutralization potency of monoclonal antibodies recognizing dominant and subdominant epitopes on SARS-CoV-2 Spike is impacted by the B.1.1.7 variant

被引：104

作者：

Graham, Carl ^{[1
]}

Seow, Jeffrey ^{[1
]}

Huettner, Isabella ^{[1
]}

Khan, Hataf ^{[1
]}

Kouphou, Neophytos ^{[1
]}

Acors, Sam ^{[1
]}

Winstone, Helena ^{[1
]}

Pickering, Suzanne ^{[1
]}

Galao, Rui Pedro ^{[1
]}

Dupont, Liane ^{[1
]}

Lista, Maria Jose ^{[1
]}

Jimenez-Guardeno, Jose M. ^{[1
]}

Laing, Adam G. ^{[2
]}

Wu, Yin ^{[2
,3
]}

Joseph, Magdalene ^{[2
,3
]}

Muir, Luke ^{[4
]}

van Gils, Marit J. ^{[5
]}

Ng, Weng M. ^{[6
]}

Duyvesteyn, Helen M. E. ^{[6
]}

Zhao, Yuguang ^{[6
]}

Bowden, Thomas A. ^{[6
]}

Shankar-Hari, Manu ^{[1
]}

Rosa, Annachiara ^{[3
]}

Cherepanov, Peter ^{[3
]}

McCoy, Laura E. ^{[4
]}

Hayday, Adrian C. ^{[2
,3
]}

Neil, Stuart J. D. ^{[1
,7
]}

Malim, Michael H. ^{[1
,7
]}

Doores, Katie J. ^{[1
,7
]}

机构：

[1] Kings Coll London, Sch Immunol & Microbial Sci, Dept Infect Dis, London, England

[2] Kings Coll London, Sch Immunol & Microbial Sci, Peter Gorer Dept Immunobiol, London, England

[3] Francis Crick Inst, London, England

[4] UCL, Div Infect & Immun, London, England

[5] Univ Amsterdam, Acad Med Ctr, Amsterdam Inst Infect & Immun, Dept Med Microbiol, Amsterdam, Netherlands

[6] Univ Oxford, Wellcome Ctr Human Genet, Div Struct Biol, Oxford, England

[7] Genotype To Phenotype UK Natl Virol Consortium, London, England

来源：

IMMUNITY | 2021年 / 54卷 / 06期

基金：

英国医学研究理事会; 英国惠康基金;

关键词：

RECEPTOR-BINDING DOMAIN; B-CELLS; MUTATIONS; EFFICIENT; REVEAL; SYSTEM; BROAD;

D O I：

10.1016/j.immuni.2021.03.023

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Interaction of the SARS-CoV-2 Spike receptor binding domain (RBD) with the receptor ACE2 on host cells is essential for viral entry. RBD is the dominant target for neutralizing antibodies, and several neutralizing epitopes on RBD have been molecularly characterized. Analysis of circulating SARS-CoV-2 variants has revealed mutations arising in the RBD, N-terminal domain (NTD) and S2 subunits of Spike. To understand how these mutations affect Spike antigenicity, we isolated and characterized >100 monoclonal antibodies targeting epitopes on RBD, NTD, and S2 from SARS-CoV-2-infected individuals. Approximately 45% showed neutralizing activity, of which similar to 20% were NTD specific. NTD-specific antibodies formed two distinct groups: the first was highly potent against infectious virus, whereas the second was less potent and displayed glycandependant neutralization activity. Mutations present in B.1.1.7 Spike frequently conferred neutralization resistance to NTD-specific antibodies. This work demonstrates that neutralizing antibodies targeting subdominant epitopes should be considered when investigating antigenic drift in emerging variants.

引用

页码：1276 / +

页数：20

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