RT Journal Article
SR Electronic
T1 SARS-CoV-2 B.1.617.2 Delta variant emergence, replication and sensitivity to neutralising antibodies
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/2021/07/16/2021.05.08.443253.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, 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.Competing Interest StatementThe authors have declared no competing interest.