Rapid engineering of SARS-CoV-2 therapeutic antibodies to increase breadth of neutralization including BQ.1.1, CA.3.1, CH.1.1, XBB.1.16, and XBB.1.5.

SARS-CoV-2 Omicron variant XBB.1.5 has shown extraordinary immune escape even for fully vaccinated individuals. There are currently no approved antibodies that neutralize this variant, and continued emergence of new variants puts immunocompromised and elderly patients at high risk. Rapid and cost-effective development of neutralizing antibodies is urgently needed. Starting with a single parent clone that neutralized the Wuhan-Hu-1 strain, antibody engineering was performed in iterative stages in real time as variants emerged using a proprietary technology called STage-Enhanced Maturation. An antibody panel that broadly neutralizes currently circulating Omicron variants was obtained by in vitro affinity maturation using phage display. The engineered antibodies show potent neutralization of BQ.1.1, XBB.1.16, and XBB.1.5 by surrogate virus neutralization test and pM K_D affinity for all variants. Our work not only details novel therapeutic candidates but also validates a unique general strategy to create broadly neutralizing antibodies to current and future SARS-CoV-2 variants.