Rapid engineering of SARS-CoV-2 therapeutic antibodies to increase breadth of neutralization including XBB.1.5 and BQ.1.1

Abstract

An antibody panel that broadly neutralizes currently circulating Omicron variants was obtained by in vitro affinity maturation using phage display. Starting from a single parent clone, antibody engineering was performed in iterative stages in real time as variants emerged using a proprietary technology called STage-Enhanced Maturation (STEM). Humanized from a rabbit antibody, the parent clone showed undetectable neutralization of later Omicron variants, while an early stage IgG possessing only an engineered light chain potently neutralizes some BA.2 but not BA.4/BA.5 lineage variants. However, the final heavy and light chain engineered mAbs show potent neutralization of XBB.1.5 and BQ.1.1 by surrogate virus neutralization test, and biolayer interferometry shows pM KD affinity for both variants. Our work not only details novel therapeutic candidates but also validates a unique general strategy to create broadly neutralizing mAbs to current and future SARS-CoV-2 variants.