An emerging SARS-CoV-2 mutant evades cellular immunity and increases infectivity

Many variants that naturally acquire multiple mutations have emerged during the current SARS-CoV-2 pandemic, which is devastating societies worldwide. Emerging mutations can affect viral properties such as infectivity and immune resistance. Although the sensitivity of naturally occurring SARS-CoV-2 variants to humoral immunity has recently been investigated, sensitivity to human leukocyte antigen (HLA)-restricted cellular immunity remains unaddressed. Here, we demonstrate that two recently emerging mutations in the receptor-binding domain of the SARS-CoV-2 spike protein, L452R (in B.1.427/429) and Y453F (in B.1.1.298), confer escape from HLA-A24-restricted cellular immunity. These mutations reinforce the affinity toward the viral receptor ACE2; notably, the L452R mutation increases spike stability, viral infectivity, viral fusogenicity, and thereby promotes viral replication. Our data suggest that HLA-restricted cellular immunity potentially affects the evolution of viral phenotypes and that a further threat of the SARS-CoV-2 pandemic is escape from cellular immunity.