Rapid escape of new SARS-CoV-2 Omicron variants from BA.2-directed antibody responses.
Dijokaite-Guraliuc A., Das R., Zhou D., Ginn HM., Liu C., Duyvesteyn HME., Huo J., Nutalai R., Supasa P., Selvaraj M., de Silva TI., Plowright M., Newman TAH., Hornsby H., Mentzer AJ., Skelly D., Ritter TG., Temperton N., Klenerman P., Barnes E., Dunachie SJ., OPTIC consortium None., Roemer C., Peacock TP., Paterson NG., Williams MA., Hall DR., Fry EE., Mongkolsapaya J., Ren J., Stuart DI., Screaton GR.
In November 2021, Omicron BA.1, containing a raft of new spike mutations, emerged and quickly spread globally. Intense selection pressure to escape the antibody response produced by vaccines or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection then led to a rapid succession of Omicron sub-lineages with waves of BA.2 and then BA.4/5 infection. Recently, many variants have emerged such as BQ.1 and XBB, which carry up to 8 additional receptor-binding domain (RBD) amino acid substitutions compared with BA.2. We describe a panel of 25 potent monoclonal antibodies (mAbs) generated from vaccinees suffering BA.2 breakthrough infections. Epitope mapping shows potent mAb binding shifting to 3 clusters, 2 corresponding to early-pandemic binding hotspots. The RBD mutations in recent variants map close to these binding sites and knock out or severely knock down neutralization activity of all but 1 potent mAb. This recent mAb escape corresponds with large falls in neutralization titer of vaccine or BA.1, BA.2, or BA.4/5 immune serum.