SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion
Petra Mlčochová(University of Cambridge), Steven A. Kemp(University of Cambridge), Mahesh Shanker Dhar(National Center for Disease Control), Guido Papa(MRC Laboratory of Molecular Biology), Bo Meng(University of Cambridge), Isabella A.T.M. Ferreira(University of Cambridge), Rawlings Datir(University of Cambridge), Dami A. Collier(University of Cambridge), Anna Albecka(MRC Laboratory of Molecular Biology), Sujeet Kumar Singh(National Center for Disease Control), Rajesh Pandey(Institute of Genomics and Integrative Biology), Jonathan C. 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 A. Mellan(Imperial College London), Robin Marwal(National Center for Disease Control), Meena Datta(National Center for Disease Control), Shantanu Sengupta(Institute of Genomics and Integrative Biology), Kalaiarasan Ponnusamy(National Center for Disease Control), Venkatraman Radhakrishnan(National Center for Disease Control), Adam Abdullahi(University of Cambridge), Oscar Charles(University College London), Partha Chattopadhyay(Institute of Genomics and Integrative Biology), Priti Devi(Institute of Genomics and Integrative Biology), Daniela Caputo(NIHR BioResource), Tom Peacock(Imperial College London), Chand Wattal(Sir Ganga Ram Hospital), Neeraj Goel(Sir Ganga Ram Hospital), Ambrish Satwik(Sir Ganga Ram Hospital), Raju Vaishya(Indraprastha Apollo Hospitals), Meenakshi Agarwal(South Eastern Railway), Himanshu Chauhan(National Center for Disease Control), Tanzin Dikid(National Center for Disease Control), Hema Gogia(National Center for Disease Control), Hemlata Lall(National Center for Disease Control), Kaptan Verma(National Center for Disease Control), Mahesh Shanker Dhar(National Center for Disease Control), Manoj Kumar Singh(National Center for Disease Control), Namita Soni(National Center for Disease Control), Namonarayan Meena(National Center for Disease Control), Preeti Madan(National Center for Disease Control), Priyanka Singh(National Center for Disease Control), Ramesh Sharma(National Center for Disease Control), Rajeev Sharma(National Center for Disease Control), Sandhya Kabra(National Center for Disease Control), Sattender Kumar(National Center for Disease Control), Swati Kumari(National Center for Disease Control), Uma Sharma(National Center for Disease Control), Urmila Chaudhary(National Center for Disease Control), Sridhar Sivasubbu(Institute of Genomics and Integrative Biology), Vinod Scaria(Institute of Genomics and Integrative Biology), Jaspal Kaur Oberoi(Sir Ganga Ram Hospital), Reena Raveendran(Sir Ganga Ram Hospital), Sandip K. Datta(Sir Ganga Ram Hospital), Saumitra Das(National Institute of Biomedical Genomics), Arindam Maitra(National Institute of Biomedical Genomics), Sreedhar Chinnaswamy(National Institute of Biomedical Genomics), Nidhan K. Biswas(National Institute of Biomedical Genomics), Ajay Parida(Institute of Life Sciences), Sunil K. Raghav(Institute of Life Sciences), Punit Prasad(Institute of Life Sciences), Apurva Sarin(Institute for Stem Cell Biology and Regenerative Medicine), Satyajit Mayor(Institute for Stem Cell Biology and Regenerative Medicine), Uma Ramakrishnan(Institute for Stem Cell Biology and Regenerative Medicine), Dasaradhi Palakodeti(Institute for Stem Cell Biology and Regenerative Medicine), Aswin Sai Narain Seshasayee(Institute for Stem Cell Biology and Regenerative Medicine), Kumarasamy Thangaraj(Centre for DNA Fingerprinting and Diagnostics), Murali Dharan Bashyam(Centre for DNA Fingerprinting and Diagnostics), Ashwin Dalal(Centre for DNA Fingerprinting and Diagnostics), Manoj Kumar Bhat(National Centre for Cell Science), Yogesh S. Shouche(National Centre for Cell Science), Ajay D. Pillai(National Centre for Cell Science), Priya Abraham(ICMR-National Institute of Virology), Varsha Potdar(ICMR-National Institute of Virology), Sarah Cherian(ICMR-National Institute of Virology), Anita Desai(National Institute of Mental Health and Neurosciences), Chitra Pattabiraman(National Institute of Mental Health and Neurosciences), M. V. Manjunatha(National Institute of Mental Health and Neurosciences), Reeta S. Mani(National Institute of Mental Health and Neurosciences), Gautam Arunachal Udupi(National Institute of Mental Health and Neurosciences), Vinay Kumar Nandicoori(Centre for Cellular and Molecular Biology), Karthik Bharadwaj Tallapaka(Centre for Cellular and Molecular Biology), Divya Tej Sowpati(Centre for Cellular and Molecular Biology), Ryoko Kawabata(Hiroshima University), Nanami Morizako(Hiroshima University), Kenji Sadamasu(Tokyo Metropolitan Institute of Public Health), Hiroyuki Asakura(Tokyo Metropolitan Institute of Public Health), Mami Nagashima(Tokyo Metropolitan Institute of Public Health), Kazuhisa Yoshimura(Tokyo Metropolitan Institute of Public Health), Jumpei Ito(The University of Tokyo), Izumi Kimura(The University of Tokyo), Keiya Uriu(The University of Tokyo), Yusuke Kosugi(The University of Tokyo), Mai Suganami(The University of Tokyo), Akiko Oide(The University of Tokyo), Miyabishara Yokoyama(The University of Tokyo), Mika Chiba(The University of Tokyo), Akatsuki Saito(University of Miyazaki), Erika P. Butlertanaka(University of Miyazaki), Yuri Tanaka(University of Miyazaki), Terumasa Ikeda(Kumamoto University), Chihiro Motozono(Kumamoto University), Hesham Nasser(Kumamoto University), Ryo Shimizu(Kumamoto University), Yue Yuan(Kumamoto University), Kazuko Kitazato(Kumamoto University), Haruyo Hasebe(Kumamoto University), So Nakagawa(Tokai University), Jiaqi Wu(Tokai University), Miyoko Takahashi(Tokai University), Takasuke Fukuhara(Hokkaido University), Kenta Shimizu(Hokkaido University), Kana Tsushima(Hokkaido University), Haruko Kubo(Hokkaido University), Kotaro Shirakawa(Kyoto University), Yasuhiro Kazuma(Kyoto University), Ryosuke Nomura(Kyoto University), Yoshihito Horisawa(Kyoto University), Akifumi Takaori‐Kondo(Kyoto University), Kenzo Tokunaga(National Institute of Infectious Diseases), Seiya Ozono(National Institute of Infectious Diseases), Stephen Baker(University of Cambridge), Gordon Dougan(University of Cambridge), Christoph Hess(University of Cambridge), Nathalie Kingston(NIHR BioResource), Paul J. Lehner(University of Cambridge), Paul Lyons(University of Cambridge), Nicholas J. Matheson(University of Cambridge), Willem H. Owehand(Africa Health Research Institute), Caroline Saunders(University of Oxford), Charlotte Summers(University of Cambridge), James Thaventhiran(University of Cambridge), Mark Toshner(University of Cambridge), Michael P. Weekes(University of Cambridge), Patrick H. Maxwell(Cambridge University Hospitals NHS Foundation Trust), Ashley Shaw(Cambridge University Hospitals NHS Foundation Trust), Ashlea Bucke(Cambridge University Hospitals NHS Foundation Trust), Jo Calder(Cambridge University Hospitals NHS Foundation Trust), Laura Canna(Cambridge University Hospitals NHS Foundation Trust), Jason Domingo(Cambridge University Hospitals NHS Foundation Trust), Anne Elmer(Cambridge University Hospitals NHS Foundation Trust), Stewart Fuller(Cambridge University Hospitals NHS Foundation Trust), Julie Harris(Cambridge University Hospitals NHS Foundation Trust), Sarah Hewitt(Cambridge University Hospitals NHS Foundation Trust), Jane Kennet(Cambridge University Hospitals NHS Foundation Trust), Sherly Jose(Cambridge University Hospitals NHS Foundation Trust), Jenny Kourampa(Cambridge University Hospitals NHS Foundation Trust), Anne Meadows(Cambridge University Hospitals NHS Foundation Trust), Criona O’Brien(Cambridge University Hospitals NHS Foundation Trust), Jane Price(Cambridge University Hospitals NHS Foundation Trust), Cherry Publico(Cambridge University Hospitals NHS Foundation Trust), Rebecca Rastall(Cambridge University Hospitals NHS Foundation Trust), Carla M. S. Ribeiro(Cambridge University Hospitals NHS Foundation Trust), Jane Rowlands(Cambridge University Hospitals NHS Foundation Trust), Valentina Ruffolo(Cambridge University Hospitals NHS Foundation Trust), Hugo Tordesillas(Cambridge University Hospitals NHS Foundation Trust), Ben Bullman, Benjamin J. Dunmore(University of Cambridge), Stuart Fawke(University of Cambridge), Stefan Ting Graf(University of Cambridge), Josh Hodgson(National Center for Disease Control), Christopher Huang(National Center for Disease Control), Kelvin Hunter(University of Cambridge), Emma Jones(University of Miyazaki), Ekaterina Legchenko(University of Cambridge), Cecilia Matara(University of Cambridge), Jennifer Martin(University of Cambridge), Federica Mescia(University of Cambridge), Ciara O’Donnell(University of Cambridge), Linda Pointon(University of Cambridge), Nicole Pond(University of Cambridge), Joy Shih(University of Cambridge), Rachel Sutcliffe(University of Cambridge), Tobias Tilly(University of Cambridge), Carmen Treacy(University of Cambridge), Zhen Tong(University of Cambridge), Jennifer Wood(University of Cambridge), Marta Wylot(University of Cambridge), Laura Bergamaschi(University of Cambridge), Ariana Betancourt(University of Cambridge), Georgie Bower(University of Cambridge), Chiara Cossetti(University of Cambridge), Aloka De(University of Cambridge), Madeline Epping(University of Cambridge), Stuart Fawke(University of Cambridge), Nick Gleadall(University of Cambridge), Richard Grenfell(University of Cambridge), Andrew Hinch(University of Cambridge), Oisín Huhn(University of Cambridge), Sarah Jackson(University of Cambridge), Isobel Jarvis(University of Cambridge), Benjamin A. Krishna(University of Cambridge), Daniel J. Lewis(National Center for Disease Control), Joe Marsden(National Center for Disease Control), Francesca Nice(University of Cambridge), Georgina Okecha(University College London), Ommar Omarjee(University of Cambridge), Marianne Perera(University of Cambridge), Martin Potts(University of Cambridge), Nathan Richoz(University of Cambridge), Veronika Romashova(University of Cambridge), Natalia Savinykh Yarkoni(National Center for Disease Control), Rahul Sharma(National Center for Disease Control), Luca Stefanucci(University of Cambridge), Jonathan Stephens(Africa Health Research Institute), Mateusz Strezlecki(University of Cambridge), Lori Turner(University of Cambridge), Eckart M. D. D. De Bie(University of Cambridge), Katherine Bunclark(University of Cambridge), Maša Josipović(University of Cambridge), Michael Mackay(University of Cambridge), Sabrina Rossi(Cambridge University Hospitals NHS Foundation Trust), Mayurun Selvan(National Center for Disease Control), Sarah Spencer(Vir Biotechnology (Switzerland)), Cissy Yong(Cambridge University Hospitals NHS Foundation Trust), John Allison(NIHR BioResource), Helen Butcher(University of Cambridge), Daniela Caputo(University of Cambridge), Debbie Clapham-Riley(University of Cambridge), Eleanor Dewhurst(University of Cambridge), Anita Furlong(University of Cambridge), Barbara Graves(University of Cambridge), Jennifer Gray(University of Cambridge), Tasmin Ivers(University of Cambridge), Mary Kasanicki(Centre for Cellular and Molecular Biology), Emma Le Gresley(University of Cambridge), Rachel Linger(University of Cambridge), Sarah Meloy(University of Cambridge), Francesca Muldoon(University of Cambridge), Nigel Ovington(NIHR BioResource), Sofia Papadia(University of Cambridge), Isabel Phelan(University of Cambridge), Hannah Stark(University of Cambridge), Kathleen Stirrups(South Eastern Railway), Paul Townsend(University of Cambridge), Neil Walker(University of Cambridge), Jennifer Webster(University of Cambridge), Ingrid Scholtes(University of Cambridge), Sabine Hein(University of Cambridge), Rebecca L. King(University of Cambridge), Antranik Mavousian(Wellcome/MRC Cambridge Stem Cell Institute), Joo Hyeon Lee(Wellcome/MRC Cambridge Stem Cell Institute), Jessica Bassi(Vir Biotechnology (Switzerland)), Chiara Silacci-Fegni(Vir Biotechnology (Switzerland)), Christian Saliba(Vir Biotechnology (Switzerland)), Dora Pinto(Vir Biotechnology (Switzerland)), Takashi Irie(Hiroshima University), Isao Yoshida(Tokyo Metropolitan Institute of Public Health), William L. Hamilton(University of Cambridge), Kei Sato(Japan Science and Technology Agency), Samir Bhatt(National Center for Disease Control), Seth Flaxman(University of Oxford), Leo C. James(MRC Laboratory of Molecular Biology), Davide Corti(Vir Biotechnology (Switzerland)), Luca Piccoli(Vir Biotechnology (Switzerland)), William Barclay(Imperial College London), Partha Rakshit(National Center for Disease Control), Anurag Agrawal(Institute of Genomics and Integrative Biology), Ravindra K. Gupta(University of Cambridge)
Cited by 1,418Open Access
Abstract
. 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.
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