RT Journal Article SR Electronic T1 SARS-CoV-2 B.1.617.2 Delta variant replication, sensitivity to neutralising antibodies and vaccine breakthrough JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.05.08.443253 DO 10.1101/2021.05.08.443253 A1 Petra Mlcochova A1 Steven Kemp A1 Mahesh Shanker Dhar A1 Guido Papa A1 Bo Meng A1 Swapnil Mishra A1 Charlie Whittaker A1 Thomas Mellan A1 Isabella Ferreira A1 Rawlings Datir A1 Dami A. Collier A1 Anna Albecka A1 Sujeet Singh A1 Rajesh Pandey A1 Jonathan Brown A1 Jie Zhou A1 Niluka Goonawardne A1 Robin Marwal A1 Meena Datta A1 Shantanu Sengupta A1 Kalaiarasan Ponnusamy A1 Venkatraman Srinivasan Radhakrishnan A1 Adam Abdullahi A1 Oscar Charles A1 Partha Chattopadhyay A1 Priti Devi A1 Daniela Caputo A1 Tom Peacock A1 Chand Wattal A1 Neeraj Goel A1 Ambrish Satwik A1 Raju Vaishya A1 Meenakshi Agarwal A1 The Indian SARS-CoV-2 Genomics Consortium (INSACOG) A1 The CITIID-NIHR BioResource COVID-19 Collaboration A1 The Genotype to Phenotype Japan (G2P-Japan) Consortium A1 Antranik Mavousian A1 Joo Hyeon Lee A1 Jessica Bassi A1 Chiara Silacci-Fegni A1 Christian Saliba A1 Dora Pinto A1 Takashi Irie A1 Isao Yoshida A1 William L. Hamilton A1 Kei Sato A1 Leo James A1 Davide Corti A1 Luca Piccoli A1 Samir Bhatt A1 Seth Flaxman A1 Wendy S. Barclay A1 Partha Rakshit A1 Anurag Agrawal A1 Ravindra K. Gupta YR 2021 UL http://biorxiv.org/content/early/2021/08/06/2021.05.08.443253.abstract AB 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, outcompeting pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha). In vitro, B.1.617.2 is 6-fold less sensitive to serum neutralising antibodies from recovered individuals, and 8-fold less sensitive to vaccine-elicited antibodies as compared to wild type Wuhan-1 bearing D614G. Serum neutralising titres against B.1.617.2 were lower in ChAdOx-1 versus BNT162b2 vaccinees. 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 bamlavinimab 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. Additionally we observed that B.1.617.2 had higher replication and spike mediated entry as compared to B.1.617.1, potentially explaining B.1.617.2 dominance. In an analysis of over 130 SARS-CoV-2 infected healthcare workers across three centres in India during a period of mixed lineage circulation, we observed substantially reduced ChAdOx-1 vaccine efficacy against B.1.617.2 relative to non-B.1.617.2. 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.Competing Interest StatementThe authors have declared no competing interest.