Antibody evasion of SARS-CoV-2 Omicron BA.1, BA.1.1, BA.2, and BA.3 sub-lineages

The SARS-CoV-2 Omicron variant has evolved into four sub-lineages-BA.1, BA.1.1, BA.2, and BA.3-with BA.2 becoming dominant worldwide. We and others have reported antibody evasion of BA.1 and BA.2, but side-by-side comparisons of Omicron sub-lineages to vaccine-elicited or monoclonal antibody (mAb)-mediated neutralization are necessary. Using VSV-based pseudovirus, we report that sera from individuals vaccinated by two doses of an inactivated whole-virion vaccine shows weak to no neutralization activity, while homologous or heterologous boosters markedly improve neutralization titers against all Omicron sub-lineages. We also present neutralization profiles against a 20 mAb panel, including 10 authorized or approved, against the Omicron sub-lineages, along with mAb mapping against single or combinatorial spike mutations. Most mAbs lost neutralizing activity, while some demonstrate distinct neutralization patterns among Omicron sub-lineages, reflecting antigenic differences. Collectively, our results suggest the Omicron sub-lineages threaten the neutralization efficacy of current vaccines and antibody therapeutics, highlighting the importance of vaccine boosters.