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SARS-CoV-2 B.1.617.2 Delta variant emergence and vaccine breakthrough

Petra Mlcochova, Steven Kemp, Mahesh Shanker Dhar, Guido Papa, Bo Meng, Swapnil Mishra, Charlie Whittaker, Thomas Mellan, Isabella Ferreira, Rawlings Datir, Dami A. Collier, Sujeet Singh, Rajesh Pandey, Robin Marwal, Meena Datta, Shantanu Sengupta, Kalaiarasan Ponnusamy, V.S. Radhakrishnan, Adam Abdullahi, Niluka Goonawardne, Jonathan Brown, Oscar Charles, Partha Chattopadhyay, Priti Devi, Daniela Caputo, Tom Peacock, Dr Chand Wattal, Neeraj Goel, Raju Vaishya, Meenakshi Agarwal, The Indian SARS-CoV-2 Genomics Consortium (INSACOG), The CITIID-NIHR BioResource COVID-19 Collaboration, Antranik Mavousian, Joo Hyeon Lee, Wendy S. Barclay, Samir Bhatt, Seth Flaxman, Leo James, 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
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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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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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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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V.S. 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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Niluka Goonawardne
8Department of Infectious Diseases, Imperial College London, UK
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Jonathan Brown
8Department of Infectious Diseases, Imperial College London, 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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Dr 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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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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Wendy S. Barclay
8Department of Infectious Diseases, Imperial College London, UK
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Samir Bhatt
4MRC – Laboratory of Molecular Biology, Cambridge, UK
15Section of Epidemiology, Department of Public Health, University of Copenhagen, Denmark
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Seth Flaxman
16Department of Mathematics, Imperial College London, London, UK
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Leo James
4MRC – Laboratory of Molecular Biology, Cambridge, 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
17Africa 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 has spread throughout India, displacing the B.1.1.7 (Alpha) variant and other pre-existing lineages. Mathematical modelling indicates that the growth advantage is most likely explained by a combination of increased transmissibility and immune evasion. Indeed in vitro, the delta variant is less sensitive to neutralising antibodies in sera from recovered individuals, with higher replication efficiency as compared to the Alpha variant. In an analysis of vaccine breakthrough in over 100 healthcare workers across three centres in India, the Delta variant was responsible for greater transmission between HCW as compared to B.1.1.7 or B.1.617.1 (mean cluster size 3.2 versus 1.1, p<0.05). In vitro, the Delta variant shows 8 fold approximately reduced sensitivity to vaccine-elicited antibodies compared to wild type Wuhan-1 bearing D614G. Serum neutralising titres against the SARS-CoV-2 Delta variant were significantly lower in participants vaccinated with ChadOx-1 as compared to BNT162b2 (GMT 3372 versus 654, p<0001). These combined epidemiological and in vitro data indicate that the dominance of the Delta variant in India has been most likely driven by a combination of evasion of neutralising antibodies in previously infected individuals and increased virus infectivity. Whilst severe disease in fully vaccinated HCW was rare, breakthrough transmission clusters in hospitals associated with the Delta variant are concerning and indicate that infection control measures need continue in the post-vaccination era.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • This version is focused now on Delta variant has two more hospital case studies; the 617.1 double mutant data now moved to another manuscript specifically on the B.1.617.1

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-NC-ND 4.0 International license.
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SARS-CoV-2 B.1.617.2 Delta variant emergence and vaccine breakthrough
Petra Mlcochova, Steven Kemp, Mahesh Shanker Dhar, Guido Papa, Bo Meng, Swapnil Mishra, Charlie Whittaker, Thomas Mellan, Isabella Ferreira, Rawlings Datir, Dami A. Collier, Sujeet Singh, Rajesh Pandey, Robin Marwal, Meena Datta, Shantanu Sengupta, Kalaiarasan Ponnusamy, V.S. Radhakrishnan, Adam Abdullahi, Niluka Goonawardne, Jonathan Brown, Oscar Charles, Partha Chattopadhyay, Priti Devi, Daniela Caputo, Tom Peacock, Dr Chand Wattal, Neeraj Goel, Raju Vaishya, Meenakshi Agarwal, The Indian SARS-CoV-2 Genomics Consortium (INSACOG), The CITIID-NIHR BioResource COVID-19 Collaboration, Antranik Mavousian, Joo Hyeon Lee, Wendy S. Barclay, Samir Bhatt, Seth Flaxman, Leo James, 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 and vaccine breakthrough
Petra Mlcochova, Steven Kemp, Mahesh Shanker Dhar, Guido Papa, Bo Meng, Swapnil Mishra, Charlie Whittaker, Thomas Mellan, Isabella Ferreira, Rawlings Datir, Dami A. Collier, Sujeet Singh, Rajesh Pandey, Robin Marwal, Meena Datta, Shantanu Sengupta, Kalaiarasan Ponnusamy, V.S. Radhakrishnan, Adam Abdullahi, Niluka Goonawardne, Jonathan Brown, Oscar Charles, Partha Chattopadhyay, Priti Devi, Daniela Caputo, Tom Peacock, Dr Chand Wattal, Neeraj Goel, Raju Vaishya, Meenakshi Agarwal, The Indian SARS-CoV-2 Genomics Consortium (INSACOG), The CITIID-NIHR BioResource COVID-19 Collaboration, Antranik Mavousian, Joo Hyeon Lee, Wendy S. Barclay, Samir Bhatt, Seth Flaxman, Leo James, 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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