Antibody evasiveness of SARS-CoV-2 subvariants KP.3.1.1 and XEC

SARS-CoV-2 continues to evolve and spread around the world, and it remains critical to understand the functional consequences of mutations that lead to dominant viral variants. KP.3.1.1 is currently the most prevalent subvariant worldwide, while the recombinant subvariant XEC is exhibiting the fastest growth rate. Here we measured the in vitro neutralization of KP.3.1.1 and XEC by human sera, monoclonal antibodies, and soluble hACE2 receptor relative to their parental subvariants KP.3 and JN.1. KP.3.1.1 and XEC were slightly more resistant (1.3-1.6-fold) than KP.3 to serum neutralization, and the resultant antigenic map showed that the new subvariants are antigenically similar. Both also demonstrated greater resistance to neutralization by select monoclonal antibodies and soluble hACE2, all of which target the top of the viral spike. Our findings suggested that upward motion of the receptor-binding domain in spike is partially hindered by the N-terminal-domain mutations found KP.3.1.1 and XEC, thereby allowing these subvariants to better evade serum antibodies that target the viral spike when it is in the up position and thus having a growth advantage in the population.