TY - JOUR T1 - SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion. JF - Nature Y1 - 2021 A1 - Mlcochova, Petra A1 - Kemp, Steven A A1 - Dhar, Mahesh Shanker A1 - Papa, Guido A1 - Meng, Bo A1 - Ferreira, Isabella A T M A1 - Datir, Rawlings A1 - Collier, Dami A A1 - Albecka, Anna A1 - Singh, Sujeet A1 - Pandey, Rajesh A1 - Brown, Jonathan A1 - Zhou, Jie A1 - Goonawardane, Niluka A1 - Mishra, Swapnil A1 - Whittaker, Charles A1 - Mellan, Thomas A1 - Marwal, Robin A1 - Datta, Meena A1 - Sengupta, Shantanu A1 - Ponnusamy, Kalaiarasan A1 - Radhakrishnan, Venkatraman Srinivasan A1 - Abdullahi, Adam A1 - Charles, Oscar A1 - Chattopadhyay, Partha A1 - Devi, Priti A1 - Caputo, Daniela A1 - Peacock, Tom A1 - Wattal, Chand A1 - Goel, Neeraj A1 - Satwik, Ambrish A1 - Vaishya, Raju A1 - Agarwal, Meenakshi A1 - Mavousian, Antranik A1 - Lee, Joo Hyeon A1 - Bassi, Jessica A1 - Silacci-Fegni, Chiara A1 - Saliba, Christian A1 - Pinto, Dora A1 - Irie, Takashi A1 - Yoshida, Isao A1 - Hamilton, William L A1 - Sato, Kei A1 - Bhatt, Samir A1 - Flaxman, Seth A1 - James, Leo C A1 - Corti, Davide A1 - Piccoli, Luca A1 - Barclay, Wendy S A1 - Rakshit, Partha A1 - Agrawal, Anurag A1 - Gupta, Ravindra K KW - Antibodies, Neutralizing KW - Cell Fusion KW - Cell Line KW - COVID-19 Vaccines KW - Female KW - Health Personnel KW - Humans KW - Immune Evasion KW - India KW - Kinetics KW - Male KW - SARS-CoV-2 KW - Spike Glycoprotein, Coronavirus KW - Vaccination KW - Virus Replication AB -

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). In vitro, B.1.617.2 is sixfold less sensitive to serum neutralizing antibodies from recovered individuals, and eightfold less sensitive to vaccine-elicited antibodies, compared with wild-type Wuhan-1 bearing D614G. Serum neutralizing titres against B.1.617.2 were lower in ChAdOx1 vaccinees than in BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies to the receptor-binding domain and the amino-terminal domain. B.1.617.2 demonstrated higher replication efficiency than B.1.1.7 in both airway organoid and human airway epithelial 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 was 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 replication and spike-mediated entry than B.1.617.1, potentially explaining the B.1.617.2 dominance. In an analysis of more than 130 SARS-CoV-2-infected health care workers across three centres in India during a period of mixed lineage circulation, we observed reduced ChAdOx1 vaccine effectiveness against B.1.617.2 relative to non-B.1.617.2, with the caveat of possible residual confounding. Compromised vaccine efficacy against the highly fit and immune-evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era.

VL - 599 IS - 7883 ER -