SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion

The B.1.617.2 (Delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in the state of Maharashtra in late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha)¹. B.1.617.2 is sixfold less sensitive to serum neutralizing antibodies from recovered individuals, and B.1.617.2 showed reduced neutralization with monoclonal antibodies, compared with wild-type viruses. The spike's additional mutations exhibited compromised sensitivity to monoclonal antibodies due to steric hindrance at the amino-terminal domain. B.1.617.2 demonstrates higher replication efficiency than B.1.1.7 in both airway organoids and in various experimental systems, associated with B.1.617.2 spike being in a predominantly cleaved state compared with B.1.1.7 spike. The B.1.617.2 spike protein is able to mediate highly efficient syncytium formation that was less sensitive to inhibition by neutralizing antibody, compared with that of wild-type spike. We also observed that B.1.617.2 had higher receptor binding and spike-mediated entry than B.1.617.1, potentially explaining the B.1.617.2 dominance. In an analysis of more than 1,130 SARS-CoV-2-infected health care workers across three trends in India during a period of mixed lineage circulation, we observed reduced ChAdOx vaccine effectiveness against B.1.617.2 relative to non-B.1.617.2, with the caveat of possible residual confounding. Compromised vaccine effectiveness against the highly fit and immune-evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era.