TY - JOUR
T1 - Emerging variants develop total escape from potent monoclonal antibodies induced by BA.4/5 infection
AU - Liu, Chang
AU - Das, Raksha
AU - Dijokaite-Guraliuc, Aiste
AU - Zhou, Daming
AU - Mentzer, Alexander J.
AU - Supasa, Piyada
AU - Selvaraj, Muneeswaran
AU - Duyvesteyn, Helen M.E.
AU - Ritter, Thomas G.
AU - Temperton, Nigel
AU - Klenerman, Paul
AU - Dunachie, Susanna J.
AU - Paterson, Neil G.
AU - Williams, Mark A.
AU - Hall, David R.
AU - Fry, Elizabeth E.
AU - Mongkolsapaya, Juthathip
AU - Ren, Jingshan
AU - Stuart, David I.
AU - Screaton, Gavin R.
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/12
Y1 - 2024/12
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85190464788
U2 - 10.1038/s41467-024-47393-3
DO - 10.1038/s41467-024-47393-3
M3 - Article
C2 - 38627386
AN - SCOPUS:85190464788
SN - 2041-1723
VL - 15
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 3284
ER -
