The sequences of the authentic viruses used in this study have been deposited to GISAID (https://www.gisaid.org/)?under the accession numbers EPI_ISL_497840 (D614G) and EPI_ISL_9845731 (BA.2). unique spike alterations and lacking 13 spike alterations found in BA.1. Here we extended our studies to D77 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. 2C4,6). 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). Subject terms: SARS-CoV-2, Vaccines, Viral immune evasion, Antiviral agents A study reports on the antigenic characterization of SARS-CoV-2 BA.1, BA.1.1 and BA.2 and the neutralizing activity of different monoclonal antibodies and sera against them. Main The rise of the Omicron (B.1.1.529) variant to become the dominant variant of SARS-CoV-2 globally has been remarkable8. Continuing surveillance of its evolution in the population in December 2021 and January 2022 has revealed that the proportion of the original form, BA.1, has been decreasing steadily whereas the proportions of two other sublineages have increased noticeably (Fig. D77 ?(Fig.1a).1a). In fact, the BA.1+R346K sublineage now accounts for about 40% of Omicron sequences globally, and about 35C60% in New Zealand, the UK and the USA. On the other hand, D77 the BA.2 sublineage accounts for only about 10% of Omicron sequences globally, but it is not only on the rise but also the dominant form in countries such as Denmark, India and South Africa. These three sublineages of Omicron share 21 alterations in the spike protein, wherein BA.2 contains 8 unique alterations and BA.1 contains 13 unique alterations (Fig. ?(Fig.1b).1b). Of course, BA.1+R346K has one alteration more than BA.1. Given these differences, their antigenic properties cannot be assumed IL22 antibody to be the same or similar. Open in a separate window 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. values were determined by a two-sided Friedman test followed by Dunns multiple comparisons test. Serum neutralization of sublineages Therefore, we first investigated the sensitivity of the Omicron sublineages to neutralization by polyclonal sera from D77 convalescent individuals or individuals given mRNA vaccines, with or without a booster shot. These serum samples, as well as the pseudovirus neutralization assay used, were identical to ones previously reported2. The wild-type D614G pseudovirus was included as a comparator. As was observed and reported for BA.1 (refs. 2,3,5,6), a marked and significant loss of neutralizing activity of the serum against BA.1+R346K and BA.2 relative to.