University of Nebraska Medical Center

Fast evolution of SARS-CoV-2 BA.2·86 to JN.1 under heavy immune pressure

The Lancet

The SARS-CoV-2 saltation variant BA.2.86, which was quickly designated as a variant under monitoring after its emergence, has garnered global attention. Although BA.2.86 did not show substantial humoral immune escape and growth advantage compared with current dominant variants, such as EG.5.1 and HK.3, it showed remarkably high ACE2 binding affinity. This increased binding affinity, coupled with its distinct antigenicity, could enable BA.2.86 to accumulate immune-evasive mutations during low-level populational transmission, akin to the previous evolution from BA.2.75 to CH.1.1 and XBB. 

With just one additional receptor binding domain mutation (L455S) compared to its predecessor BA.2.86, the JN.1 variant rapidly became predominant in France (figure Aappendix 1 p 12), surpassing both BA.2.86 and the so-called FLip (L455F+F456L) strains. A thorough investigation into the immune evasion capability of JN.1, particularly given its few additional mutations, is imperative.

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