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

Petra Mlcochova, Steven A. Kemp, Mahesh Shanker Dhar, Guido Papa, Bo Meng, Isabella A. T. M. Ferreira, Rawlings Datir, Dami A. Collier, Anna Albecka, Sujeet Singh, Rajesh Pandey, Jonathan Brown, Jie Zhou, Niluka Goonawardane, Swapnil Mishra, Charles Whittaker, Thomas Mellan, 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, Antranik Mavousian, Joo Hyeon Lee, Jessica Bassi, Chiara Silacci-Fegni, Christian Saliba, Dora Pinto, Takashi Irie, Isao Yoshida, William L. Hamilton, Kei Sato, Samir Bhatt, Seth Flaxman, Leo C. James, Davide Corti, Luca Piccoli, Wendy S. Barclay, Partha Rakshit (), Anurag Agrawal () and Ravindra K. Gupta ()
Additional contact information
Petra Mlcochova: Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID)
Steven A. Kemp: Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID)
Mahesh Shanker Dhar: National Centre for Disease Control
Guido Papa: MRC – Laboratory of Molecular Biology
Bo Meng: Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID)
Isabella A. T. M. Ferreira: Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID)
Rawlings Datir: Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID)
Dami A. Collier: University of Cambridge
Anna Albecka: MRC – Laboratory of Molecular Biology
Sujeet Singh: National Centre for Disease Control
Rajesh Pandey: CSIR Institute of Genomics and Integrative Biology
Jonathan Brown: Imperial College London
Jie Zhou: Imperial College London
Niluka Goonawardane: Imperial College London
Swapnil Mishra: Imperial College London
Charles Whittaker: Imperial College London
Thomas Mellan: Imperial College London
Robin Marwal: National Centre for Disease Control
Meena Datta: National Centre for Disease Control
Shantanu Sengupta: CSIR Institute of Genomics and Integrative Biology
Kalaiarasan Ponnusamy: National Centre for Disease Control
Venkatraman Srinivasan Radhakrishnan: National Centre for Disease Control
Adam Abdullahi: Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID)
Oscar Charles: University College London
Partha Chattopadhyay: CSIR Institute of Genomics and Integrative Biology
Priti Devi: CSIR Institute of Genomics and Integrative Biology
Daniela Caputo: NIHR Bioresource
Tom Peacock: Imperial College London
Chand Wattal: Sri Ganga Ram Hospital
Neeraj Goel: Sri Ganga Ram Hospital
Ambrish Satwik: Sri Ganga Ram Hospital
Raju Vaishya: Indraprastha Apollo Hospital
Meenakshi Agarwal: Northern Railway Central Hospital
Antranik Mavousian: Wellcome-MRC Cambridge Stem Cell Institute
Joo Hyeon Lee: Wellcome-MRC Cambridge Stem Cell Institute
Jessica Bassi: Humabs Biomed SA, a subsidiary of Vir Biotechnology
Chiara Silacci-Fegni: Humabs Biomed SA, a subsidiary of Vir Biotechnology
Christian Saliba: Humabs Biomed SA, a subsidiary of Vir Biotechnology
Dora Pinto: Humabs Biomed SA, a subsidiary of Vir Biotechnology
Takashi Irie: Hiroshima University
Isao Yoshida: Tokyo Metropolitan Institute of Public Health
William L. Hamilton: University of Cambridge
Kei Sato: The University of Tokyo
Samir Bhatt: National Centre for Disease Control
Seth Flaxman: University of Oxford
Leo C. James: MRC – Laboratory of Molecular Biology
Davide Corti: Humabs Biomed SA, a subsidiary of Vir Biotechnology
Luca Piccoli: Humabs Biomed SA, a subsidiary of Vir Biotechnology
Wendy S. Barclay: Imperial College London
Partha Rakshit: National Centre for Disease Control
Anurag Agrawal: CSIR Institute of Genomics and Integrative Biology
Ravindra K. Gupta: Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID)

Nature, 2021, vol. 599, issue 7883, 114-119

Abstract: Abstract 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.

Date: 2021
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DOI: 10.1038/s41586-021-03944-y

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