SARS-CoV-2 B.1.617.2 Delta variant emergence, replication and sensitivity to neutralising antibodies

Abstract The SARS-CoV-2 B.1.617.2 (Delta) variant was first identified in the state of Maharashtra in late 2020 and spread throughout India, displacing the B.1.1.7 (Alpha) variant and other pre-existing lineages, including B.1.617.1 that was detected prior to B.1.617.2. Bayesian modelling indicates that the growth advantage of B.1.617.2 in Mumbai was most likely explained by increased transmissibility and immune evasion from previous infection. Indeed in vitro, we demonstrate that B.1.617.2 is approximately 6-fold less sensitive to neutralising antibodies in sera from recovered individuals, and approximately 8-fold less sensitive to vaccine-elicited antibodies as compared to wild type Wuhan-1 bearing D614G. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies against the receptor binding domain (RBD) and N-terminal domain (NTD), in particular to the clinically approved bamvalinumb and imdevimab monoclonal antibodies. B.1.617.2 demonstrated higher replication efficiency in both airway organoid and human airway epithelial systems as compared to B.1.1.7, associated with B.1.617.2 spike being in a predominantly cleaved state compared to B.1.1.7. In an analysis of vaccinated healthcare workers across three centres in India during a period of mixed lineage circulation, we observed reduced ChAdOx-1 vaccine efficacy against B.1.617.2 relative to non-B.1.617.2. These combined epidemiological and in vitro data indicate that the dominance of B.1.617.2 in India has been most likely driven by a combination of evasion of neutralising antibodies in previously infected individuals and increased virus infectivity. B.1.617.2 threatens the efficacy of critically important therapeutic monoclonal antibodies for COVID-19 and compromised vaccine efficacy mandates continued infection control measures in the post-vaccination era.