Antigenic cartography of SARS-CoV-2 reveals that Omicron BA.1 and BA.2 are antigenically distinct.

The emergence and rapid spread of SARS-CoV-2 variants may affect vaccine efficacy substantially. The Omicron variant termed BA.2, which differs substantially from BA.1 based on genetic sequence, is currently replacing BA.1 in several countries, but its antigenic characteristics have not yet been assessed. Here, we used antigenic cartography to quantify and visualize antigenic differences between early SARS-CoV-2 variants (614G, Alpha, Beta, Gamma, Zeta, Delta, and Mu) using hamster antisera obtained after primary infection. We first verified that the choice of the cell line for the neutralization assay did not affect the topology of the map substantially. Antigenic maps generated using pseudo-typed SARS-CoV-2 on the widely used VeroE6 cell line and the human airway cell line Calu-3 generated similar maps. Maps made using authentic SARS-CoV-2 on Calu-3 cells also closely resembled those generated with pseudo-typed viruses. The antigenic maps revealed a central cluster of SARS-CoV-2 variants, which grouped on the basis of mutual spike mutations. Whereas these early variants are antigenically similar, clustering relatively close to each other in antigenic space, Omicron BA.1 and BA.2 have evolved as two distinct antigenic outliers. Our data show that BA.1 and BA.2 both escape vaccine-induced antibody responses as a result of different antigenic characteristics. Thus, antigenic cartography could be used to assess antigenic properties of future SARS-CoV-2 variants of concern that emerge and to decide on the composition of novel spike-based (booster) vaccines. Coronavirus cartography: The emergence of new SARS-CoV-2 variants continues to initiate fresh waves of COVID-19 infection across the globe. Antigenic cartography is an established method for assessing the degree of antigenic difference based on the capacity of polyclonal antibodies to distinct viral variants to neutralize an array of related viruses. Mykytyn et al. applied antigenic cartography to SARS-CoV-2 variants by generating hamster antisera to individual variants and assessing their ability to neutralize variants up to Omicron BA.2. This analysis revealed Omicron BA.1 and BA.2 as outlier variants that are quite different from each other and a cluster of earlier SARS-CoV-2 variants. Analysis of cross-neutralization via antigenic cartography may be of value in making decisions on updating the spike antigen are used in future SARS-CoV-2 vaccines. [ABSTRACT FROM AUTHOR]