Emerging variants develop total escape from potent monoclonal antibodies induced by BA.4/5 infection
Chang Liu, Raksha Das, Aiste Dijokaite-Guraliuc, Daming Zhou, Alexander J. Mentzer, Piyada Supasa, Muneeswaran Selvaraj, Helen M. E. Duyvesteyn, Thomas Ritter, Nigel Temperton, Paul Klenerman, Susanna Dunachie, Neil G. Paterson, Mark A. Williams, David R. Hall, Elizabeth E. Fry, Juthathip Mongkolsapaya, Jingshan Ren, David I. Stuart, Gavin Screaton
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.