A structure-function analysis shows SARS-CoV-2 BA.2.86 balances antibody escape and ACE2 affinity

BA.2.86, a recently described sublineage of SARS-CoV-2 Omicron, contains many mutations in the spike gene. It appears to have originated from BA.2 and is distinct from the XBB variants responsible for many infections in 2023. The global spread and plethora of mutations in BA.2.86 has caused concern that it may possess greater immune-evasive potential, leading to a new wave of infection. Here, we examine the ability of BA.2.86 to evade the antibody response to infection using a panel of vaccinated or naturally infected sera and find that it shows marginally less immune evasion than XBB.1.5. We locate BA.2.86 in the antigenic landscape of recent variants and look at its ability to escape panels of potent monoclonal antibodies generated against contemporary SARS-CoV-2 infections. We demonstrate, and provide a structural explanation for, increased affinity of BA.2.86 to ACE2, which may increase transmissibility. [Display omitted] •BA.2.86, highly mutated from BA.2, is mapped in the landscape of recent variants•It is marginally less evasive than XBB.1.5 but escapes a panel of BA.2 antibodies•It has increased affinity for ACE2, possibly aiding transmission•Its RBD is primed for further escape at residues 455 and/or 456, as seen in JN.1 BA.2.86 spike has evolved extensively from the early Omicron variant BA.2, allowing it to escape the vast majority of anti-BA.2 monoclonal antibodies. While it is not quite as evasive as some other recent variants such as XBB.1.5, it has high affinity for the virus receptor ACE2 and is primed for further antigenic escape by mutation at residues 455 and/or 456 of the spike.