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SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion - Nature.com

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, outcompeting pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha)1. 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 (WT) 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). B.1.617.2 demonstrated higher replication efficiency in both airway organoid and human airway epithelial systems compared to B.1.1.7, associated with B.1.617.2 spike in a predominantly cleaved state compared to B.1.1.7. The B.1.617.2 spike protein was able to mediate highly efficient syncytium formation that was less sensitive to inhibition by neutralising antibody as compared to WT spike. 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 reduced ChAdOx-1 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.

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Author notes

  1. These authors contributed equally: Petra Mlcochova, Steven Kemp, Mahesh Shanker Dhar, Partha Rakshit, Anurag Agrawal and Ravindra K. Gupta

Affiliations

  1. Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Cambridge, UK

    Petra Mlcochova, Steven Kemp, Bo Meng, Isabella A. T. M. Ferreira, Rawlings Datir, Adam Abdullahi, Stephen Baker, Gordon Dougan, Paul J. Lehner, Paul A. Lyons, Nicholas J. Matheson, Ben Bullman & Ravindra K. Gupta

  2. Department of Medicine, University of Cambridge, Cambridge, UK

    Petra Mlcochova, Steven Kemp, Bo Meng, Isabella A. T. M. Ferreira, Rawlings Datir, Dami A. Collier, Adam Abdullahi, Stephen Baker, Gordon Dougan, Christoph Hess, Paul J. Lehner, Paul A. Lyons, Nicholas J. Matheson, Charlotte Summers, James E. D. Thaventhiran, Mark Toshner, Michael P. Weekes, Benjamin J. Dunmore, Stefan Gräf, Kelvin Hunter, Ekaterina Legchenko, Cecilia Matara, Jennifer Martin, Federica Mescia, Ciara O’Donnell, Linda Pointon, Nicole Pond, Joy Shih, Rachel Sutcliffe, Tobias Tilly, Carmen Treacy, Zhen Tong, Jennifer Wood, Marta Wylot, Laura Bergamaschi, Ariana Betancourt, Georgie Bower, Chiara Cossetti, Aloka De Sa, Madeline Epping, Stuart Fawke, Nick Gleadall, Richard Grenfell, Andrew Hinch, Sarah Jackson, Isobel Jarvis, Ben Krishna, Ommar Omarjee, Marianne Perera, Martin Potts, Nathan Richoz, Veronika Romashova, Luca Stefanucci, Mateusz Strezlecki, Lori Turner, Eckart M. D. D. De Bie, Katherine Bunclark, Masa Josipovic, Michael Mackay, William L. Hamilton & Ravindra K. Gupta

  3. University College London, London, UK

    Steven Kemp, Dami A. Collier, Oscar Charles & Georgina Okecha

  4. National Centre for Disease Control, Delhi, India

    Mahesh Shanker Dhar, Sujeet Singh, Robin Marwal, Meena Datta, Kalaiarasan Ponnusamy, Venkatraman Srinivasan Radhakrishnan, Himanshu Chauhan, Tanzin Dikid, Hema Gogia, Hemlata Lall, Kaptan Verma, Mahesh S. Dhar, Manoj K. Singh, Namita Soni, Namonarayan Meena, Preeti Madan, Priyanka Singh, Ramesh Sharma, Rajeev Sharma, Sandhya Kabra, Sattender Kumar, Swati Kumari, Uma Sharma, Urmila Chaudhary, Josh Hodgson, Christopher Huang, Daniel Lewis, Joe Marsden, Natalia Savinykh Yarkoni, Rahul Sharma, Mayurun Selvan, Samir Bhatt & Partha Rakshit

  5. MRC – Laboratory of Molecular Biology, Cambridge, UK

    Guido Papa, Anna Albecka & Leo C. James

  6. CSIR Institute of Genomics and Integrative Biology, Delhi, India

    Rajesh Pandey, Sridhar Sivasubbu & Vinod Scaria

  7. Department of Infectious Diseases, Imperial College London, London, UK

    Jonathan Brown, Jie Zhou, Niluka Goonawardane, Shantanu Sengupta, Partha Chattopadhyay, Priti Devi & Anurag Agrawal

  8. Medical Research Council (MRC) Centre for Global Infectious Disease Analysis, Jameel Institute, School of Public Health, Imperial College London, London, UK

    Swapnil Mishra, Charles Whittaker, Thomas Mellan, Tom Peacock & Wendy S. Barclay

  9. NIHR Bioresource, Cambridge, UK

    Daniela Caputo, Nathalie Kingston, John Allison, Helen Butcher, Daniela Caputo, Debbie Clapham-Riley, Eleanor Dewhurst, Anita Furlong, Barbara Graves, Jennifer Gray, Tasmin Ivers, Mary Kasanicki, Emma Le Gresley, Rachel Linger, Sarah Meloy, Francesca Muldoon, Nigel Ovington, Sofia Papadia, Isabel Phelan, Hannah Stark & Jennifer Webster

  10. Sri Ganga Ram Hospital, New Delhi, India

    Dr Chand Wattal, Neeraj Goel, Ambrish Satwik, Chand Wattal, J. K. Oberoi, Reena Raveendran & S. Datta

  11. Indraprastha Apollo Hospital, New Delhi, India

    Raju Vaishya

  12. Northern Railway Central Hospital, New Delhi, India

    Meenakshi Agarwal & Kathleen E. Stirrups

  13. Wellcome-MRC Cambridge Stem Cell Institute, Cambridge, UK

    Antranik Mavousian & Joo Hyeon Lee

  14. Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK

    Joo Hyeon Lee

  15. Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500, Bellinzona, Switzerland

    Sarah Spencer, Jessica Bassi, Chiara Silacci-Fegni, Christian Saliba, Dora Pinto, Davide Corti & Luca Piccoli

  16. Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, 7348551, Japan

    Ryoko Kawabata, Nanami Morizako & Takashi Irie

  17. Tokyo Metropolitan Institute of Public Health, Tokyo, 1690073, Japan

    Kenji Sadamasu, Hiroyuki Asakura, Mami Nagashima, Kazuhisa Yoshimura & Isao Yoshida

  18. Division of Systems Virology, The Institute of Medical Science, The University of Tokyo, Tokyo, 1088639, Japan

    Jumpei Ito, Izumi Kimura, Keiya Uriu, Yusuke Kosugi, Mai Suganami, Akiko Oide, Miyabishara Yokoyama, Mika Chiba & Kei Sato

  19. CREST, Japan Science and Technology Agency, Saitama, 3220012, Japan

    Kei Sato

  20. Section of Epidemiology, Department of Public Health, University of Copenhagen, Copenhagen, Denmark

    Samir Bhatt

  21. Department of Mathematics, Imperial College London, London, UK

    Caroline Saunders & Seth Flaxman

  22. Africa Health Research Institute, Durban, South Africa

    Willem H. Owehand, Jonathan Stephens, Kathleen E. Stirrups & Ravindra K. Gupta

  23. National Institute of Biomedical Genomics, Kalyani, West Bengal, India

    Saumitra Das, Arindam Maitra, Sreedhar Chinnaswamy & Nidhan Kumar Biswas

  24. Institute of Life Sciences (ILS), Bhubaneswar, India

    Ajay Parida, Sunil K. Raghav & Punit Prasad

  25. InSTEM/ NCBS, Bangalore, India

    Apurva Sarin, Satyajit Mayor, Uma Ramakrishnan, Dasaradhi Palakodeti & Aswin Sai Narain Seshasayee

  26. Centre for DNA Fingerprinting and Diagnostics, Hyderabad, India

    K. Thangaraj, Murali Dharan Bashyam & Ashwin Dalal

  27. National Centre for Cell Science, Pune, India

    Manoj Bhat, Yogesh Shouche & Ajay Pillai

  28. National Institute of Virology, Pune, India

    Priya Abraham, Potdar Varsha Atul & Sarah S. Cherian

  29. National Institute of Mental Health and Neuroscience, Bangalore, India

    Anita Sudhir Desai, Chitra Pattabiraman, M. V. Manjunatha, Reeta S. Mani & Gautam Arunachal Udupi

  30. Centre for Cellular and Molecular Biology, Hyderabad, India

    Vinay Nandicoori, Karthik Bharadwaj,  Tallapaka, Divya Tej Sowpati & Mary Kasanicki

  31. University of Miyazaki, Miyazaki, Japan

    Akatsuki Saito, Erika P. Butlertanaka, Yuri L. Tanaka & Emma Jones

  32. Kumamoto University, Kumamoto, Japan

    Terumasa Ikeda, Chihiro Motozono, Hesham Nasser, Ryo Shimizu, Yue Yuan, Kazuko Kitazato & Haruyo Hasebe

  33. Tokai University, Tokyo, Japan

    So Nakagawa, Jiaqi Wu & Miyoko Takahashi

  34. Hokkaido University, Sapporo, Japan

    Takasuke Fukuhara, Kenta Shimizu, Kana Tsushima & Haruko Kubo

  35. Kyoto University, Kyoto, Japan

    Kotaro Shirakawa, Yasuhiro Kazuma, Ryosuke Nomura, Yoshihito Horisawa & Akifumi Takaori-Kondo

  36. National Institute of Infectious Diseases, Tokyo, Japan

    Kenzo Tokunaga & Seiya Ozono

  37. Cambridge University Hospitals NHS Trust, Cambridge, UK

    Patrick Maxwell, Ashley Shaw, Alice Michael, Sabrina Rossi & Cissy Yong

  38. Cambridge Clinical Research Centre, NIHR Clinical Research Facility, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke’s Hospital, Cambridge, CB2 0QQ, UK

    Ashlea Bucke, Jo Calder, Laura Canna, Jason Domingo, Anne Elmer, Stewart Fuller, Julie Harris, Sarah Hewitt, Jane Kennet, Sherly Jose, Jenny Kourampa, Anne Meadows, Criona O’Brien, Jane Price, Cherry Publico, Rebecca Rastall, Carla Ribeiro, Jane Rowlands, Valentina Ruffolo & Hugo Tordesillas

  39. Department of Biochemistry, University of Cambridge, Cambridge, CB2 1QW, UK

    Stuart Fawke & Oisin Huhn

  40. University of Cambridge, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK

    Francesca Nice, Helen Butcher, Daniela Caputo, Debbie Clapham-Riley, Eleanor Dewhurst, Anita Furlong, Barbara Graves, Jennifer Gray, Tasmin Ivers, Emma Le Gresley, Rachel Linger, Sarah Meloy, Francesca Muldoon, Sofia Papadia, Isabel Phelan, Hannah Stark, Paul Townsend, Neil Walker, Jennifer Webster, Ingrid Scholtes, Sabine Hein & Rebecca King

Authors
  1. Petra Mlcochova
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  2. Steven Kemp
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  52. Ravindra K. Gupta
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  • , Barbara Graves
  • , Jennifer Gray
  • , Tasmin Ivers
  • , Mary Kasanicki
  • , Emma Le Gresley
  • , Rachel Linger
  • , Sarah Meloy
  • , Francesca Muldoon
  • , Nigel Ovington
  • , Sofia Papadia
  • , Isabel Phelan
  • , Hannah Stark
  • , Kathleen E. Stirrups
  • , Paul Townsend
  • , Neil Walker
  • , Jennifer Webster
  • , Ingrid Scholtes
  • , Sabine Hein
  •  & Rebecca King

Corresponding authors

Correspondence to Partha Rakshit or Anurag Agrawal or Ravindra K. Gupta.

Supplementary information

Supplementary Information

This file contains acknowledgements of the following authors from the Originating laboratories responsible for obtaining the specimens, as well as the submitting laboratories where the genome data were generated and shared via GISAID on which this research is based.

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Mlcochova, P., Kemp, S., Dhar, M.S. et al. SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion. Nature (2021). https://ift.tt/3jPgjQp

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