TY - JOUR T1 - Antibody Resistance of SARS-CoV-2 Omicron BA.1, BA.1.1, BA.2 and BA.3 Sub-lineages JF - bioRxiv DO - 10.1101/2022.04.07.487489 SP - 2022.04.07.487489 AU - Jingwen Ai AU - Xun Wang AU - Xinyi He AU - Xiaoyu Zhao AU - Yi Zhang AU - Yuchao Jiang AU - Minghui Li AU - Yuchen Cui AU - Yanjia Chen AU - Rui Qiao AU - Lin Li AU - Lulu Yang AU - Yi Li AU - Zixin Hu AU - Wenhong Zhang AU - Pengfei Wang Y1 - 2022/01/01 UR - http://biorxiv.org/content/early/2022/04/07/2022.04.07.487489.abstract N2 - The SARS-CoV-2 Omicron variant has been partitioned into four sub-lineages designated BA.1, BA.1.1, BA.2 and BA.3, with BA.2 becoming dominant worldwide recently by outcompeting BA.1 and BA.1.1. We and others have reported the striking antibody evasion of BA.1 and BA.2, but side-by-side comparison of susceptibility of all the major Omicron sub-lineages to vaccine-elicited or monoclonal antibody (mAb)-mediated neutralization are urgently needed. Using VSV-based pseudovirus, we found that sera from individuals vaccinated by two doses of inactivated whole-virion vaccines (BBIBP-CorV) showed very weak to no neutralization activity, while a homologous inactivated vaccine booster or a heterologous booster with protein subunit vaccine (ZF2001) markedly improved the neutralization titers against all Omicron variants. The comparison between sub-lineages indicated that BA.1.1, BA.2 and BA.3 had comparable or even greater antibody resistance than BA.1. We further evaluated the neutralization profile of a panel of 20 mAbs, including 10 already authorized or approved, against these Omicron sub-lineages as well as viruses with different Omicron spike single or combined mutations. Most mAbs lost their neutralizing activity completely or substantially, while some demonstrated distinct neutralization patterns among Omicron sub-lineages, reflecting their antigenic difference. Taken together, our results suggest all four Omicron sub-lineages threaten the efficacies of current vaccines and antibody therapeutics, highlighting the importance of vaccine boosters to combat the emerging SARS-CoV-2 variants.Competing Interest StatementP.W. is an inventor on patent applications on some of the antibodies described in this manuscript. Others have no conflict of interest. ER -