RT Journal Article SR Electronic T1 Antibody Resistance of SARS-CoV-2 Omicron BA.1, BA.1.1, BA.2 and BA.3 Sub-lineages JF bioRxiv FD Cold Spring Harbor Laboratory SP 2022.04.07.487489 DO 10.1101/2022.04.07.487489 A1 Jingwen Ai A1 Xun Wang A1 Xinyi He A1 Xiaoyu Zhao A1 Yi Zhang A1 Yuchao Jiang A1 Minghui Li A1 Yuchen Cui A1 Yanjia Chen A1 Rui Qiao A1 Lin Li A1 Lulu Yang A1 Yi Li A1 Zixin Hu A1 Wenhong Zhang A1 Pengfei Wang YR 2022 UL http://biorxiv.org/content/early/2022/04/07/2022.04.07.487489.abstract AB 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.