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. 2022 Apr;604(7906):553-556.
doi: 10.1038/s41586-022-04594-4. Epub 2022 Mar 3.

Antibody evasion properties of SARS-CoV-2 Omicron sublineages

Sho Iketani #  1   2 , Lihong Liu #  1 , Yicheng Guo #  1 , Liyuan Liu #  3 , Jasper F-W Chan #  4   5 , Yiming Huang  3 , Maple Wang  1 , Yang Luo  1 , Jian Yu  1 , Hin Chu  4   5 , Kenn K-H Chik  4   5 , Terrence T-T Yuen  4 , Michael T Yin  1   6 , Magdalena E Sobieszczyk  1   6 , Yaoxing Huang  1 , Kwok-Yung Yuen  4   5 , Harris H Wang  3   7 , Zizhang Sheng  1 , David D Ho  8   9   10
Affiliations

Antibody evasion properties of SARS-CoV-2 Omicron sublineages

Sho Iketani et al. Nature. 2022 Apr.

Abstract

The identification of the Omicron (B.1.1.529.1 or BA.1) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Botswana in November 20211 immediately caused concern owing to the number of alterations in the spike glycoprotein that could lead to antibody evasion. We2 and others3-6 recently reported results confirming such a concern. Continuing surveillance of the evolution of Omicron has since revealed the rise in prevalence of two sublineages, BA.1 with an R346K alteration (BA.1+R346K, also known as BA.1.1) and B.1.1.529.2 (BA.2), with the latter containing 8 unique spike alterations and lacking 13 spike alterations found in BA.1. Here we extended our studies to include antigenic characterization of these new sublineages. Polyclonal sera from patients infected by wild-type SARS-CoV-2 or recipients of current mRNA vaccines showed a substantial loss in neutralizing activity against both BA.1+R346K and BA.2, with drops comparable to that already reported for BA.1 (refs. 2,3,5,6). These findings indicate that these three sublineages of Omicron are antigenically equidistant from the wild-type SARS-CoV-2 and thus similarly threaten the efficacies of current vaccines. BA.2 also exhibited marked resistance to 17 of 19 neutralizing monoclonal antibodies tested, including S309 (sotrovimab)7, which had retained appreciable activity against BA.1 and BA.1+R346K (refs. 2-4,6). This finding shows that no authorized monoclonal antibody therapy could adequately cover all sublineages of the Omicron variant, except for the recently authorized LY-CoV1404 (bebtelovimab).

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Conflict of interest statement

S.I., Lihong Liu, J.Y., Yaoxing Huang and D.D.H. are inventors on patent applications (WO2021236998) or provisional patent applications (63/271,627) filed by Columbia University for a number of SARS-CoV-2 neutralizing antibodies described in this manuscript. Both sets of applications are under review. D.D.H. is a co-founder of TaiMed Biologics and RenBio, consultant to WuXi Biologics and Brii Biosciences, and board director for Vicarious Surgical.

Figures

Fig. 1
Fig. 1. BA.2 exhibits a similar serum neutralization profile to those of BA.1 sublineages.
a, Proportions of BA.1, BA.1+R346K and BA.2 in B.1.1.529 sequences on GISAID over the latter half of December 2021 and January 2022. The value in the upper right corner of each box denotes the cumulative number of Omicron sequences. b, Alterations in the B.1.1.529 lineage. NTD, N-terminal domain; RBD, receptor-binding domain; SD1, subdomain 1; SD2, subdomain 2; FP, fusion peptide; HR1, heptad repeat 1; CH, central helix; CD, connector domain; HR2, heptad repeat 2; CT, cytoplasmic tail. c, Pseudovirus neutralization by convalescent and vaccinee sera. n = 10, 12, 13 and 15 biologically independent serum samples, respectively, for convalescent, mRNA-1273, BNT162b2 and boosted groups. The values above the points indicate geometric means. The numbers in parentheses denote the numbers of samples above the limit of detection (LOD) of 100. Values below the LOD are arbitrarily plotted to allow for visualization of each sample. P values were determined by a two-sided Friedman test followed by Dunn’s multiple comparisons test.
Fig. 2
Fig. 2. BA.2 differs in resistance profile to monoclonal antibodies.
a, Pseudovirus neutralization by monoclonal antibodies (mAbs). Values above the LOD of 10 μg ml−1 (dotted line) are arbitrarily plotted to allow for visualization of each sample. b, Fold change in IC50 values relative to D614G of neutralization of Omicron variants, as well as point mutants unique to BA.2.
Extended Data Fig. 1
Extended Data Fig. 1. Serum neutralization of authentic viruses.
Authentic virus neutralization by vaccinee sera. n = 10 and 13 biologically independent serum samples, respectively, for two doses mRNA and three doses mRNA groups. Values above points indicate the geometric mean. Numbers in parentheses denote the number of samples above the limit of detection (LOD) of 500. Values below the LOD and those that overlap are plotted to allow for visualization of each sample. P values were determined by two-sided Wilcoxon matched-pairs signed rank test.
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