Potent Cross-reactive Antibodies Following Omicron Breakthrough in Vaccinees

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2022 Jun 6

PMID 35662412

Authors

Rungtiwa Nutalai

Daming Zhou

Aekkachai Tuekprakhon

Helen M Ginn

Piyada Supasa

Chang Liu

Jiandong Huo

Alexander J Mentzer

Helen M E Duyvesteyn

Aiste Dijokaite-Guraliuc

Donal Skelly

Thomas G Ritter

Ali Amini

Sagida Bibi

Sandra Adele

Sile Ann Johnson

Bede Constantinides

Hermione Webster

Nigel Temperton

Paul Klenerman

Eleanor Barnes

Susanna J Dunachie

Derrick Crook

Andrew J Pollard

Teresa Lambe

Philip Goulder

Neil G Paterson

Mark A Williams

David R Hall

Juthathip Mongkolsapaya

Elizabeth E Fry

Wanwisa Dejnirattisai

Jingshan Ren

David I Stuart

Gavin R Screaton

Affiliations

Soon will be listed here.

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.

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