Antigenic cartography using sera from sequence-confirmed SARS-CoV-2 variants of concern infections reveals antigenic divergence of Omicron

Large-scale vaccination campaigns have prevented countless hospitalizations and deaths due to COVID-19. However, the emergence of SARS-CoV-2 variants that escape from immunity challenges the effectiveness of current vaccines. Given this continuing evolution, an important question is when and how to update SARS-CoV-2 vaccines to antigenically match circulating variants, similarly to seasonal influenza viruses where antigenic drift necessitates periodic vaccine updates. Here, we studied SARS-CoV-2 antigenic drift by assessing neutralizing activity against variants of concern (VOCs) in a set of sera from patients infected with viral sequence-confirmed VOCs. Infections with D614G or Alpha strains induced the broadest immunity, whereas individuals infected with other VOCs had more strain-specific responses. Omicron BA.1 and BA.2 were substantially resistant to neutralization by sera elicited by all other variants. Antigenic cartography revealed that Omicron BA.1 and BA.2 were antigenically most distinct from D614G, associated with immune escape, and possibly will require vaccine updates to ensure vaccine effectiveness. [Display omitted] •SARS-CoV-2 VOCs induce qualitatively different neutralizing antibody responses•D614G and Alpha induce the strongest and broadest neutralizing antibody responses•Omicron induces weaker neutralizing antibody responses•Omicron BA.1 and BA.2 are antigenically distinct from the D614G strain Given the continued evolution of SARS-CoV-2, it is important to understand when and how to update vaccines to antigenically match circulating variants. van der Straten et al. demonstrate that infection with different SARS-CoV-2 variants leads to qualitatively different neutralizing antibody responses. Moreover, they show that Omicron represents a new cluster of antigenically distinct variants, which has implications for updating vaccines.