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. 2022 Aug 10;30(8):1077-1083.e4.
doi: 10.1016/j.chom.2022.05.001. Epub 2022 May 8.

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

Jingwen Ai  1 , Xun Wang  2 , Xinyi He  3 , Xiaoyu Zhao  2 , Yi Zhang  1 , Yuchao Jiang  4 , Minghui Li  2 , Yuchen Cui  2 , Yanjia Chen  2 , Rui Qiao  2 , Lin Li  2 , Lulu Yang  2 , Yi Li  5 , Zixin Hu  6 , Wenhong Zhang  7 , Pengfei Wang  8
Affiliations

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

Jingwen Ai et al. Cell Host Microbe. .

Abstract

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.

Keywords: BA.1; BA.1.1; BA.2; BA.3; BBIBP-CorV; Omicron; SARS-CoV-2; antibody; booster; vaccine.

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Conflict of interest statement

Declaration of interests P.W. is an inventor on patent applications on some of the antibodies described in this manuscript, including 1–20, 2–15, 1–57, 2–7, 2–36, 5–24, 4–18, 4–19, and 5–7. All other authors have no conflict of interest.

Figures

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Graphical abstract
Figure 1
Figure 1
Characteristics and sera neutralization of the Omicron sub-lineages (A) Phylogenetic tree of the BA.1, BA.1.1, BA.2, and BA.3 sub-lineages. Fifty randomly selected sequences belonging to each of the Omicron sub-lineages from GISAID were used as query sequences. (B) Prevalence of the Omicron sub-lineages and Delta variant based on all the sequences available on GISAID over the past 6 months. (C) Spike mutations within the Omicron sub-lineages. (D–G) Neutralization of pseudotyped WT (D614G) and Omicron sub-lineage viruses by sera collected from individuals vaccinated with two-dose BBIBP-CorV only (D), with a BBIBP-CorV homologous booster (E), or with a ZF001 heterologous booster dose (F) following two doses of BBIBP-CorV, or from individuals infected by Delta virus after vaccination (G). For all panels, values above the symbols denote geometric mean titer, and the numbers in parentheses denote the proportion of positive sera with ID50 above the LOQ (dotted lines, >1:10). p values were determined by using a Wilcoxon matched-pairs signed-rank test (two-tailed). See also Figures S1 and S2.
Figure 2
Figure 2
Neutralization of pseudotyped WT (D614G) and Omicron sub-lineage viruses by mAbs targeting different epitopes (A) Changes in neutralization IC50 of select RBD and NTD mAbs against Omicron sub-lineage pseudoviruses. (B) Fold increase or decrease in neutralization IC50 of mAbs against Omicron sub-lineage as well as single- and combinatorial-spike mutation pseudoviruses, relative to WT, presented as a heatmap with darker colors implying greater change. See also Figure S3.
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References

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Supplementary concepts