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

• Published in: bioRxiv
• Main Authors: Mlcochova, Petra, Kemp, Steven A, Mahesh Shanker Dhar, Papa, Guido, Meng, Bo, Mishra, Swapnil, Whittaker, Charlie, Mellan, Thomas, Ferreira, Isabella, Rawlings Datir, Collier, Dami, Singh, Sujeet, Pandey, Rajesh, Ponnusamy, Kalaiarasan, Radhakrishnan, V S, Sengupta, Shantanu, Brown, Jonathan, Marwal, Robin, Radhakrishnan, Vs, Goonawardne, Niluka, Abdullahi, Adam, Devi, Priti, Chand Wattal, Caputo, Daniela, Peacock, Tom, Goel, Neeraj, Raju Vaishya, Charles, Oscar, Chattopadhyay, Partha, Agarwal, Meenakshi, Satwik, Ambrish, Consortium, Insacog, Collaboration, Nihr Bioresource, Mavousian, Antranik, Zhou, Jie, Lee, Joo Hyeon, Bassi, Jessica, Silacci-Fegni, Chiara, Saliba, Christian, Pinto, Dora, Irie, Takashi, Yoshida, Isao, Hamilton, William L, Sato, Kei, Leo, James, Corti, Davide, Piccoli, Luca, Bhatt, Samir, Flaxman, Seth, Barlcay, Wendy, Rakshit, Partha, Agrawal, Anurag, Gupta, Ravindra K
• Format: Paper
• Language: English
• Published: Cold Spring Harbor Cold Spring Harbor Laboratory Press 16.07.2021
• Subjects: Antibodies; Epidemiology; Immune evasion; Infectivity; Mathematical models; Medical personnel; Severe acute respiratory syndrome coronavirus 2; Vaccination; Vaccine efficacy; Vaccines; India
• DOI: 10.1101/2021.05.08.443253

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 not only dominates vaccine-breakthrough infections with higher respiratory viral loads compared to non-delta infections (Ct value of 16.5 versus 19), but also generates greater transmission between HCW as compared to B.1.1.7 or B.1.617.1 (mean cluster size 1.1 versus 3.3 p=0.03). 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 has new replication data and monoclonal antibody data as well as assessment of vaccine efficacy for Delta relative to Alpha and Kappa