SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion
Petra Mlčochová, Steven A. Kemp, Mahesh Shanker Dhar, Guido Papa, Bo Meng, Isabella A.T.M. Ferreira, Rawlings Datir, Dami A. Collier, Anna Albecka, Sujeet Kumar Singh, Rajesh Pandey, Jonathan C. Brown, Jie Zhou, Niluka Goonawardane, Swapnil Mishra, Charles Whittaker, Thomas A. Mellan, Robin Marwal, Meena Datta, Shantanu Sengupta, Kalaiarasan Ponnusamy, Venkatraman Radhakrishnan, Adam Abdullahi, Oscar Charles, Partha Chattopadhyay, Priti Devi, Daniela Caputo, Tom Peacock, Chand Wattal, Neeraj Goel, Ambrish Satwik, Raju Vaishya, Meenakshi Agarwal, Himanshu Chauhan, Tanzin Dikid, Hema Gogia, Hemlata Lall, Kaptan Verma, Mahesh Shanker Dhar, Manoj Kumar Singh, Namita Soni, Namonarayan Meena, Preeti Madan, Priyanka Singh, Ramesh Sharma, Rajeev Sharma, Sandhya Kabra, Sattender Kumar, Swati Kumari, Uma Sharma, Urmila Chaudhary, Sridhar Sivasubbu, Vinod Scaria, Jaspal Kaur Oberoi, Reena Raveendran, Sandip K. Datta, Saumitra Das, Arindam Maitra, Sreedhar Chinnaswamy, Nidhan K. Biswas, Ajay Parida, Sunil K. Raghav, Punit Prasad, Apurva Sarin, Satyajit Mayor, Uma Ramakrishnan, Dasaradhi Palakodeti, Aswin Sai Narain Seshasayee, Kumarasamy Thangaraj, Murali Dharan Bashyam, Ashwin Dalal, Manoj Kumar Bhat, Yogesh S. Shouche, Ajay D. Pillai, Priya Abraham, Varsha Potdar, Sarah Cherian, Anita Desai, Chitra Pattabiraman, M. V. Manjunatha, Reeta S. Mani, Gautam Arunachal Udupi, Vinay Kumar Nandicoori, Karthik Bharadwaj Tallapaka, Divya Tej Sowpati, Ryoko Kawabata, Nanami Morizako, Kenji Sadamasu, Hiroyuki Asakura, Mami Nagashima, Kazuhisa Yoshimura, Jumpei Ito, Izumi Kimura, Keiya Uriu, Yusuke Kosugi, Mai Suganami, Akiko Oide, Miyabishara Yokoyama, Mika Chiba, Akatsuki Saito
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.