Emerging Variants Develop Total Escape From Potent Monoclonal Antibodies Induced by BA.4/5 Infection

Authors

Chang Liu
Raksha Das
Aiste Dijokaite-Guraliuc
Daming Zhou
Alexander J Mentzer
Piyada Supasa
Muneeswaran Selvaraj
Helen M E Duyvesteyn
Thomas G Ritter
Nigel Temperton
Paul Klenerman
Susanna J Dunachie
Neil G Paterson
Mark A Williams
David R Hall
Elizabeth E Fry
Juthathip Mongkolsapaya
Jingshan Ren
David I Stuart
Gavin R Screaton

Publication Date

4-16-2024

Journal

Nature Communications

Abstract

The rapid evolution of SARS-CoV-2 is driven in part by a need to evade the antibody response in the face of high levels of immunity. Here, we isolate spike (S) binding monoclonal antibodies (mAbs) from vaccinees who suffered vaccine break-through infections with Omicron sub lineages BA.4 or BA.5. Twenty eight potent antibodies are isolated and characterised functionally, and in some cases structurally. Since the emergence of BA.4/5, SARS-CoV-2 has continued to accrue mutations in the S protein, to understand this we characterize neutralization of a large panel of variants and demonstrate a steady attrition of neutralization by the panel of BA.4/5 mAbs culminating in total loss of function with recent XBB.1.5.70 variants containing the so-called 'FLip' mutations at positions 455 and 456. Interestingly, activity of some mAbs is regained on the recently reported variant BA.2.86.

Keywords

Humans, Antibodies, Monoclonal, Mutation, Postoperative Complications, SARS-CoV-2, Antibodies, Neutralizing, Antibodies, Viral

Comments

Supplementary Materials

PMID: 38627386