Post by Nadica (She/Her) on Oct 26, 2024 2:50:51 GMT
Enhanced immune evasion of SARS-CoV-2 KP.3.1.1 and XEC through NTD glycosylation - Preprint Posted Oct 23, 2024
Abstract
KP.3.1.1 has surpassed KP.3 to become the new globally dominant strain, while XEC, a recombinant variant of KS.1.1/KP.3.3, is rapidly expanding across Europe and North America. Notably, both variants carry mutations, S31del of KP.3.1.1 and T22N of XEC, that could introduce new N-linked glycans on the Spike N-terminal domain (NTD), emphasizing the urgent need to assess their potential changes in viral characteristics. Here, we found that both KP.3.1.1 and XEC maintained the high ACE2-Spike binding affinity and pseudovirus infectivity of KP.3. Importantly, compared to KP.3, KP.3.1.1, and especially XEC, could further evade the neutralizing antibodies in convalescent plasma, even those elicited by KP.2-like breakthrough infections. Interestingly, both variants demonstrated increased resistance against monoclonal neutralizing antibodies targeting various epitopes on the receptor-binding domain (RBD). These suggest that the additional NTD glycosylation of KP.3.1.1 and XEC could enhance immune evasion via allosteric effects, and supports the future prevalence of XEC.
Abstract
KP.3.1.1 has surpassed KP.3 to become the new globally dominant strain, while XEC, a recombinant variant of KS.1.1/KP.3.3, is rapidly expanding across Europe and North America. Notably, both variants carry mutations, S31del of KP.3.1.1 and T22N of XEC, that could introduce new N-linked glycans on the Spike N-terminal domain (NTD), emphasizing the urgent need to assess their potential changes in viral characteristics. Here, we found that both KP.3.1.1 and XEC maintained the high ACE2-Spike binding affinity and pseudovirus infectivity of KP.3. Importantly, compared to KP.3, KP.3.1.1, and especially XEC, could further evade the neutralizing antibodies in convalescent plasma, even those elicited by KP.2-like breakthrough infections. Interestingly, both variants demonstrated increased resistance against monoclonal neutralizing antibodies targeting various epitopes on the receptor-binding domain (RBD). These suggest that the additional NTD glycosylation of KP.3.1.1 and XEC could enhance immune evasion via allosteric effects, and supports the future prevalence of XEC.