Potent cross-reactive antibodies following Omicron breakthrough in vaccinees

被引：117

作者：

Nutalai, Rungtiwa ^{[1
]}

Zhou, Daming ^{[2
,3
]}

Tuekprakhon, Aekkachai ^{[1
]}

Ginn, Helen M. ^{[4
]}

Supasa, Piyada ^{[1
]}

Liu, Chang ^{[1
,3
]}

Huo, Jiandong ^{[2
]}

Mentzer, Alexander J. ^{[1
,5
]}

Duyvesteyn, Helen M. E. ^{[2
]}

Dijokaite-Guraliuc, Aiste ^{[1
]}

Skelly, Donal ^{[5
,6
,7
]}

Ritter, Thomas G. ^{[5
]}

Amini, Ali ^{[5
,6
,8
]}

Bibi, Sagida ^{[9
]}

Adele, Sandra ^{[5
]}

Johnson, Sile Ann ^{[5
]}

Constantinides, Bede ^{[10
]}

Webster, Hermione ^{[10
]}

Temperton, Nigel ^{[11
]}

Klenerman, Paul ^{[5
,6
,8
,12
]}

Barnes, Eleanor ^{[5
,6
,8
,12
]}

Dunachie, Susanna J. ^{[5
,6
,10
,13
,14
]}

Crook, Derrick ^{[10
]}

Pollard, Andrew J. ^{[9
,12
]}

Lambe, Teresa ^{[3
,9
]}

Goulder, Philip ^{[6
,15
]}

Paterson, Neil G. ^{[4
]}

Williams, Mark A. ^{[4
]}

Hall, David R. ^{[4
]}

Mongkolsapaya, Juthathip ^{[1
,3
]}

Fry, Elizabeth E. ^{[2
]}

Dejnirattisai, Wanwisa ^{[1
]}

Ren, Jingshan ^{[2
]}

Stuart, David, I ^{[2
,3
,4
]}

Screaton, Gavin R. ^{[1
,3
]}

机构：

[1] Univ Oxford, Wellcome Ctr Human Genet, Nuffield Dept Med, Oxford, England

[2] Univ Oxford, Wellcome Ctr Human Genet, Nuffield Dept Med, Div Struct Biol, Oxford, England

[3] Univ Oxford, Chinese Acad Med Sci CAMS, Oxford Inst COI, Oxford, England

[4] Diamond Light Source Ltd, Harwell Sci & Innovat Campus, Didcot, Oxon, England

[5] Oxford Univ Hosp NHS Fdn Trust, Oxford, England

[6] Peter Medawar Bldg Pathogen Res, Oxford, England

[7] Univ Oxford, Nuffield Dept Clin Neurosci, Oxford, England

[8] Univ Oxford, Translat Gastroenterol Unit, Oxford, England

[9] Univ Oxford, Dept Paediat, Oxford Vaccine Grp, Oxford, England

[10] Univ Oxford, Nuffield Dept Med, Oxford, England

[11] Univ Kent & Greenwich, Medway Sch Pharm, Viral Pseudotype Unit, Chatham ME4 4TB, Kent, England

[12] NIHR Oxford Biomed Res Ctr, Oxford, England

[13] Univ Oxford, Ctr Trop Med & Global Hlth, Nuffield Dept Med, Oxford, England

[14] Mahidol Oxford Trop Med Res Unit, Bangkok, Thailand

[15] Univ Oxford, Dept Paediat, Oxford, England

来源：

CELL | 2022年 / 185卷 / 12期

基金：

英国惠康基金; 美国国家卫生研究院;

关键词：

NEUTRALIZATION; EXPRESSION; CLONING; SYSTEM;

D O I：

10.1016/j.cell.2022.05.014

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Highly transmissible Omicron variants of SARS-CoV-2 currently dominate globally. Here, we compare neutralization of Omicron BA.1, BA.1.1, and BA.2. BA.2 RBD has slightly higher ACE2 affinity than BA.1 and slightly reduced neutralization by vaccine serum, possibly associated with its increased transmissibility. Neutralization differences between sub-lineages for mAbs (including therapeutics) mostly arise from variation in residues bordering the ACE2 binding site; however, more distant mutations S371F (BA.2) and R346K (BA.1.1) markedly reduce neutralization by therapeutic antibody Vir-S309. In-depth structure-and function analyses of 27 potent RBD-binding mAbs isolated from vaccinated volunteers following breakthrough Omicron-BA.1 infection reveals that they are focused in two main clusters within the RBD, with potent right-shoulder antibodies showing increased prevalence. Selection and somatic maturation have optimized antibody potency in less-mutated epitopes and recovered potency in highly mutated epitopes. All 27 mAbs potently neutralize early pandemic strains, and many show broad reactivity with variants of concern.

引用

页码：2116 / +

页数：35

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