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SARS-CoV-2 B.1.617.2 Delta variant emergence, replication and sensitivity to neutralising antibodies

Petra Mlcochova, Steven Kemp, Mahesh Shanker Dhar, Guido Papa, Bo Meng, Swapnil Mishra, Charlie Whittaker, Thomas Mellan, Isabella Ferreira, Rawlings Datir, Dami A. Collier, Anna Albecka, Sujeet Singh, Rajesh Pandey, Jonathan Brown, Jie Zhou, Niluka Goonawardne, Robin Marwal, Meena Datta, Shantanu Sengupta, Kalaiarasan Ponnusamy, Venkatraman Srinivasan Radhakrishnan, Adam Abdullahi, Oscar Charles, Partha Chattopadhyay, Priti Devi, Daniela Caputo, Tom Peacock, Chand Wattal, Neeraj Goel, Ambrish Satwik, Raju Vaishya, Meenakshi Agarwal, The Indian SARS-CoV-2 Genomics Consortium (INSACOG), The CITIID-NIHR BioResource COVID-19 Collaboration, The Genotype to Phenotype Japan (G2P-Japan) Consortium, Antranik Mavousian, Joo Hyeon Lee, Jessica Bassi, Chiara Silacci-Fegni, Christian Saliba, Dora Pinto, Takashi Irie, Isao Yoshida, William L. Hamilton, Kei Sato, Leo James, Davide Corti, Luca Piccoli, Samir Bhatt, Seth Flaxman, Wendy S. Barclay, Partha Rakshit, Anurag Agrawal, View ORCID ProfileRavindra K. Gupta
doi: https://doi.org/10.1101/2021.05.08.443253
Petra Mlcochova
1Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Cambridge, UK
2Department of Medicine, University of Cambridge, Cambridge, UK
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Steven Kemp
1Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Cambridge, UK
2Department of Medicine, University of Cambridge, Cambridge, UK
6University College London, London, UK
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Mahesh Shanker Dhar
3National Centre for Disease Control, Delhi, India
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Guido Papa
4MRC – Laboratory of Molecular Biology, Cambridge, UK
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Bo Meng
1Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Cambridge, UK
2Department of Medicine, University of Cambridge, Cambridge, UK
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Swapnil Mishra
5Medical Research Council (MRC) Centre for Global Infectious Disease Analysis, Jameel Institute, School of Public Health, Imperial College London, UK
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Charlie Whittaker
5Medical Research Council (MRC) Centre for Global Infectious Disease Analysis, Jameel Institute, School of Public Health, Imperial College London, UK
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Thomas Mellan
5Medical Research Council (MRC) Centre for Global Infectious Disease Analysis, Jameel Institute, School of Public Health, Imperial College London, UK
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Isabella Ferreira
1Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Cambridge, UK
2Department of Medicine, University of Cambridge, Cambridge, UK
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Rawlings Datir
1Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Cambridge, UK
2Department of Medicine, University of Cambridge, Cambridge, UK
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Dami A. Collier
2Department of Medicine, University of Cambridge, Cambridge, UK
6University College London, London, UK
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Anna Albecka
4MRC – Laboratory of Molecular Biology, Cambridge, UK
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Sujeet Singh
3National Centre for Disease Control, Delhi, India
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Rajesh Pandey
7CSIR Institute of Genomics and Integrative Biology, Delhi, India
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Jonathan Brown
8Department of Infectious Diseases, Imperial College London, UK
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Jie Zhou
8Department of Infectious Diseases, Imperial College London, UK
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Niluka Goonawardne
8Department of Infectious Diseases, Imperial College London, UK
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Robin Marwal
3National Centre for Disease Control, Delhi, India
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Meena Datta
3National Centre for Disease Control, Delhi, India
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Shantanu Sengupta
7CSIR Institute of Genomics and Integrative Biology, Delhi, India
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Kalaiarasan Ponnusamy
3National Centre for Disease Control, Delhi, India
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Venkatraman Srinivasan Radhakrishnan
3National Centre for Disease Control, Delhi, India
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Adam Abdullahi
1Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Cambridge, UK
2Department of Medicine, University of Cambridge, Cambridge, UK
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Oscar Charles
6University College London, London, UK
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Partha Chattopadhyay
7CSIR Institute of Genomics and Integrative Biology, Delhi, India
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Priti Devi
7CSIR Institute of Genomics and Integrative Biology, Delhi, India
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Daniela Caputo
9NIHR Bioresource, Cambridge, UK
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Tom Peacock
8Department of Infectious Diseases, Imperial College London, UK
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Chand Wattal
10Sri Ganga Ram Hospital, New Delhi, India
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Neeraj Goel
10Sri Ganga Ram Hospital, New Delhi, India
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Ambrish Satwik
10Sri Ganga Ram Hospital, New Delhi, India
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Raju Vaishya
11Indraprastha Apollo Hospital, New Delhi
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Meenakshi Agarwal
12Northern Railway Central Hospital, New Delhi, India
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Antranik Mavousian
13Wellcome-MRC Cambridge Stem Cell Institute, Cambridge, UK
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Joo Hyeon Lee
13Wellcome-MRC Cambridge Stem Cell Institute, Cambridge, UK
14Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK
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Jessica Bassi
15Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland
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Chiara Silacci-Fegni
15Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland
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Christian Saliba
15Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland
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Dora Pinto
15Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland
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Takashi Irie
16Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima 7348551, Japan
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Isao Yoshida
17Tokyo Metropolitan Institute of Public Health, Tokyo 1690073, Japan
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William L. Hamilton
2Department of Medicine, University of Cambridge, Cambridge, UK
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Kei Sato
18Division of Systems Virology, The Institute of Medical Science, The University of Tokyo, Tokyo 1088639, Japan
19CREST, Japan Science and Technology Agency, Saitama 3220012, Japan
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Leo James
4MRC – Laboratory of Molecular Biology, Cambridge, UK
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Davide Corti
15Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland
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Luca Piccoli
15Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland
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Samir Bhatt
4MRC – Laboratory of Molecular Biology, Cambridge, UK
20Section of Epidemiology, Department of Public Health, University of Copenhagen, Denmark
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Seth Flaxman
21Department of Mathematics, Imperial College London, London, UK
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Wendy S. Barclay
8Department of Infectious Diseases, Imperial College London, UK
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Partha Rakshit
3National Centre for Disease Control, Delhi, India
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  • For correspondence: rkg20@cam.ac.uk a.agrawal@igib.in partho_rakshit@yahoo.com
Anurag Agrawal
7CSIR Institute of Genomics and Integrative Biology, Delhi, India
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  • For correspondence: rkg20@cam.ac.uk a.agrawal@igib.in partho_rakshit@yahoo.com
Ravindra K. Gupta
1Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Cambridge, UK
2Department of Medicine, University of Cambridge, Cambridge, UK
22Africa Health Research Institute, Durban, South Africa
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  • ORCID record for Ravindra K. Gupta
  • For correspondence: rkg20@cam.ac.uk a.agrawal@igib.in partho_rakshit@yahoo.com
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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, 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 Statement

The authors have declared no competing interest.

Footnotes

  • This version has new replication data and monoclonal antibody data as well as assessment of vaccine efficacy for Delta relative to Alpha and Kappa

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted July 16, 2021.
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SARS-CoV-2 B.1.617.2 Delta variant emergence, replication and sensitivity to neutralising antibodies
Petra Mlcochova, Steven Kemp, Mahesh Shanker Dhar, Guido Papa, Bo Meng, Swapnil Mishra, Charlie Whittaker, Thomas Mellan, Isabella Ferreira, Rawlings Datir, Dami A. Collier, Anna Albecka, Sujeet Singh, Rajesh Pandey, Jonathan Brown, Jie Zhou, Niluka Goonawardne, Robin Marwal, Meena Datta, Shantanu Sengupta, Kalaiarasan Ponnusamy, Venkatraman Srinivasan Radhakrishnan, Adam Abdullahi, Oscar Charles, Partha Chattopadhyay, Priti Devi, Daniela Caputo, Tom Peacock, Chand Wattal, Neeraj Goel, Ambrish Satwik, Raju Vaishya, Meenakshi Agarwal, The Indian SARS-CoV-2 Genomics Consortium (INSACOG), The CITIID-NIHR BioResource COVID-19 Collaboration, The Genotype to Phenotype Japan (G2P-Japan) Consortium, Antranik Mavousian, Joo Hyeon Lee, Jessica Bassi, Chiara Silacci-Fegni, Christian Saliba, Dora Pinto, Takashi Irie, Isao Yoshida, William L. Hamilton, Kei Sato, Leo James, Davide Corti, Luca Piccoli, Samir Bhatt, Seth Flaxman, Wendy S. Barclay, Partha Rakshit, Anurag Agrawal, Ravindra K. Gupta
bioRxiv 2021.05.08.443253; doi: https://doi.org/10.1101/2021.05.08.443253
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SARS-CoV-2 B.1.617.2 Delta variant emergence, replication and sensitivity to neutralising antibodies
Petra Mlcochova, Steven Kemp, Mahesh Shanker Dhar, Guido Papa, Bo Meng, Swapnil Mishra, Charlie Whittaker, Thomas Mellan, Isabella Ferreira, Rawlings Datir, Dami A. Collier, Anna Albecka, Sujeet Singh, Rajesh Pandey, Jonathan Brown, Jie Zhou, Niluka Goonawardne, Robin Marwal, Meena Datta, Shantanu Sengupta, Kalaiarasan Ponnusamy, Venkatraman Srinivasan Radhakrishnan, Adam Abdullahi, Oscar Charles, Partha Chattopadhyay, Priti Devi, Daniela Caputo, Tom Peacock, Chand Wattal, Neeraj Goel, Ambrish Satwik, Raju Vaishya, Meenakshi Agarwal, The Indian SARS-CoV-2 Genomics Consortium (INSACOG), The CITIID-NIHR BioResource COVID-19 Collaboration, The Genotype to Phenotype Japan (G2P-Japan) Consortium, Antranik Mavousian, Joo Hyeon Lee, Jessica Bassi, Chiara Silacci-Fegni, Christian Saliba, Dora Pinto, Takashi Irie, Isao Yoshida, William L. Hamilton, Kei Sato, Leo James, Davide Corti, Luca Piccoli, Samir Bhatt, Seth Flaxman, Wendy S. Barclay, Partha Rakshit, Anurag Agrawal, Ravindra K. Gupta
bioRxiv 2021.05.08.443253; doi: https://doi.org/10.1101/2021.05.08.443253

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