Potent cross-reactive antibodies following Omicron breakthrough in vaccinees

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Nutalai, Rungtiwa, Zhou, Daming, Tuekprakhon, Aekkachai, Ginn, Helen M, Supasa, Piyada, Liu, Chang, Huo, Jiandong, Mentzer, Alexander J, Duyvesteyn, Helen ME, Dijokaite-Guraliuc, Aiste et al (show 25 more authors) , Skelly, Donal, Ritter, Thomas G, Amini, Ali, Bibi, Sagida, Adele, Sandra, Johnson, Sile Ann, Constantinides, Bede, Webster, Hermione, Temperton, Nigel, Klenerman, Paul, Barnes, Eleanor, Dunachie, Susanna J, Crook, Derrick, Pollard, Andrew J, Lambe, Teresa, Goulder, Philip, Paterson, Neil G, Williams, Mark A, Hall, David R, Mongkolsapaya, Juthathip, Fry, Elizabeth E, Dejnirattisai, Wanwisa, Ren, Jingshan, Stuart, David I and Screaton, Gavin R (2022) Potent cross-reactive antibodies following Omicron breakthrough in vaccinees. CELL, 185 (12). 2116-+.

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Abstract

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.

Item Type:	Article
Uncontrolled Keywords:	OPTIC consortium, ISARIC4C consortium, Humans, Antibodies, Monoclonal, Antibodies, Viral, Epitopes, Neutralization Tests, Spike Glycoprotein, Coronavirus, COVID-19, Angiotensin-Converting Enzyme 2, SARS-CoV-2, COVID-19 Vaccines
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User:	Symplectic Admin
Date Deposited:	28 Oct 2022 14:57
Last Modified:	18 Jan 2023 19:48
DOI:	10.1016/j.cell.2022.05.014
Open Access URL:	https://doi.org/10.1016/j.cell.2022.05.014
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3165847