SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion
Authors: Mlcochova Petra , Kemp Steven A. , Dhar Mahesh Shanker , Papa Guido , Meng Bo , Ferreira Isabella A. T. M. , Datir Rawlings , Collier Dami A. , Albecka Anna , Singh Sujeet , Pandey Rajesh , Brown Jonathan , Zhou Jie , Goonawardane Niluka , Mishra Swapnil , Whittaker Charles , Mellan Thomas , Marwal Robin , Datta Meena , Sengupta Shantanu , Ponnusamy Kalaiarasan , Radhakrishnan Venkatraman Srinivasan , Abdullahi Adam , Charles Oscar , Chattopadhyay Partha , Devi Priti , Caputo Daniela , Peacock Tom , Wattal Chand , Goel Neeraj , Satwik Ambrish , Vaishya Raju , Agarwal Meenakshi ,   The Indian SARS-CoV-2 Genomics Consortium (INSACOG), Chauhan Himanshu , Dikid Tanzin , Gogia Hema , Lall Hemlata , Verma Kaptan , Dhar Mahesh Shanker , Singh Manoj K. , Soni Namita , Meena Namonarayan , Madan Preeti , Singh Priyanka , Sharma Ramesh , Sharma Rajeev , Kabra Sandhya , Kumar Sattender , Kumari Swati , Sharma Uma , Chaudhary Urmila , Sivasubbu Sridhar , Scaria Vinod , Oberoi J. K. , Raveendran Reena , Datta S. , Das Saumitra , Maitra Arindam , Chinnaswamy Sreedhar , Biswas Nidhan Kumar , Parida Ajay , Raghav Sunil K. , Prasad Punit , Sarin Apurva , Mayor Satyajit , Ramakrishnan Uma , Palakodeti Dasaradhi , Seshasayee Aswin Sai Narain , Thangaraj K. , Bashyam Murali Dharan , Dalal Ashwin , Bhat Manoj , Shouche Yogesh , Pillai Ajay , Abraham Priya , Potdar Varsha Atul , Cherian Sarah S. , Desai Anita Sudhir , Pattabiraman Chitra , Manjunatha M. V. , Mani Reeta S. , Udupi Gautam Arunachal , Nandicoori Vinay , Tallapaka Karthik Bharadwaj , Sowpati Divya Tej ,   The Genotype to Phenotype Japan (G2P-Japan) Consortium, Kawabata Ryoko , Morizako Nanami , Sadamasu Kenji , Asakura Hiroyuki , Nagashima Mami , Yoshimura Kazuhisa , Ito Jumpei , Kimura Izumi , Uriu Keiya , Kosugi Yusuke , Suganami Mai , Oide Akiko , Yokoyama Miyabishara , Chiba Mika , Saito Akatsuki , Butlertanaka Erika P. , Tanaka Yuri L. , Ikeda Terumasa , Motozono Chihiro , Nasser Hesham , Shimizu Ryo , Yuan Yue , Kitazato Kazuko , Hasebe Haruyo , Nakagawa So , Wu Jiaqi , Takahashi Miyoko , Fukuhara Takasuke , Shimizu Kenta , Tsushima Kana , Kubo Haruko , Shirakawa Kotaro , Kazuma Yasuhiro , Nomura Ryosuke , Horisawa Yoshihito , Takaori-Kondo Akifumi , Tokunaga Kenzo , Ozono Seiya ,   The CITIID-NIHR BioResource COVID-19 Collaboration, Baker Stephen , Dougan Gordon , Hess Christoph , Kingston Nathalie , Lehner Paul J. , Lyons Paul A. , Matheson Nicholas J. , Owehand Willem H. , Saunders Caroline , Summers Charlotte , Thaventhiran James E. D. , Toshner Mark , Weekes Michael P. , Maxwell Patrick , Shaw Ashley , Bucke Ashlea , Calder Jo , Canna Laura , Domingo Jason , Elmer Anne , Fuller Stewart , Harris Julie , Hewitt Sarah , Kennet Jane , Jose Sherly , Kourampa Jenny , Meadows Anne , O’Brien Criona , Price Jane , Publico Cherry , Rastall Rebecca , Ribeiro Carla , Rowlands Jane , Ruffolo Valentina , Tordesillas Hugo , Bullman Ben , Dunmore Benjamin J. , Fawke Stuart , Gräf Stefan , Hodgson Josh , Huang Christopher , Hunter Kelvin , Jones Emma , Legchenko Ekaterina , Matara Cecilia , Martin Jennifer , Mescia Federica , O’Donnell Ciara , Pointon Linda , Pond Nicole , Shih Joy , Sutcliffe Rachel , Tilly Tobias , Treacy Carmen , Tong Zhen , Wood Jennifer , Wylot Marta , Bergamaschi Laura , Betancourt Ariana , Bower Georgie , Cossetti Chiara , De Sa Aloka , Epping Madeline , Fawke Stuart , Gleadall Nick , Grenfell Richard , Hinch Andrew , Huhn Oisin , Jackson Sarah , Jarvis Isobel , Krishna Ben , Lewis Daniel , Marsden Joe , Nice Francesca , Okecha Georgina , Omarjee Ommar , Perera Marianne , Potts Martin , Richoz Nathan , Romashova Veronika , Yarkoni Natalia Savinykh , Sharma Rahul , Stefanucci Luca , Stephens Jonathan , Strezlecki Mateusz , Turner Lori , De Bie Eckart M. D. D. , Bunclark Katherine , Josipovic Masa , Mackay Michael , Rossi Sabrina , Selvan Mayurun , Spencer Sarah , Yong Cissy , Allison John , Butcher Helen , Caputo Daniela , Clapham-Riley Debbie , Dewhurst Eleanor , Furlong Anita , Graves Barbara , Gray Jennifer , Ivers Tasmin , Kasanicki Mary , Le Gresley Emma , Linger Rachel , Meloy Sarah , Muldoon Francesca , Ovington Nigel , Papadia Sofia , Phelan Isabel , Stark Hannah , Stirrups Kathleen E. , Townsend Paul , Walker Neil , Webster Jennifer , Scholtes Ingrid , Hein Sabine , King Rebecca , Mavousian Antranik , Lee Joo Hyeon , Bassi Jessica , Silacci-Fegni Chiara , Saliba Christian , Pinto Dora , Irie Takashi , Yoshida Isao , Hamilton William L. , Sato Kei , Bhatt Samir , Flaxman Seth , James Leo C. , Corti Davide , Piccoli Luca , Barclay Wendy S. , Rakshit Partha , Agrawal Anurag , Gupta Ravindra K. 
Published: September 2021

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. 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.