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

Mlcochova, P.; Kemp, S.A.; Dhar, M.S.; Papa, G.; Meng, B.; Ferreira, I.A.T.M.; Datir, R.; Collier, D.A.; Albecka, A.; Singh, S.; Pandey, R.; Brown, J.; Zhou, J.; Goonawardane, N.; Mishra, S.; Whittaker, C.; Mellan, T.; Marwal, R.; Datta, M.; Sengupta, S.; Ponnusamy, K.; Radhakrishnan, V.S.; Abdullahi, A.; Charles, O.; Chattopadhyay, P.; Devi, P.; Caputo, D.; Peacock, T.; Wattal, C.; Goel, N.; Satwik, A.; Vaishya, R.; Agarwal, M.; Chauhan, H.; Dikid, T.; Gogia, H.; Lall, H.; Verma, K.; Dhar, M.S.; Singh, M.K.; Soni, N.; Meena, N.; Madan, P.; Singh, P.; Sharma, R.; Sharma, R.; Kabra, S.; Kumar, S.; Kumari, S.; Sharma, U.; Chaudhary, U.; Sivasubbu, S.; Scaria, V.; Oberoi, J.K.; Raveendran, R.; Datta, S.; Das, S.; Maitra, A.; Chinnaswamy, S.; Biswas, N.K.; Parida, A.; Raghav, S.K.; Prasad, P.; Sarin, A.; Mayor, S.; Ramakrishnan, U.; Palakodeti, D.; Seshasayee, A.S.N.; Thangaraj, K.; Bashyam, M.D.; Dalal, A.; Bhat, M.; Shouche, Y.; Pillai, A.; Abraham, P.; Potdar, V.A.; Cherian, S.S.; Desai, A.S.; Pattabiraman, C.; Manjunatha, M.V.; Mani, R.S.; Udupi, G.A.; Nandicoori, V.; Tallapaka, K.B.; Sowpati, D.T.; Kawabata, R.; Morizako, N.; Sadamasu, K.; Asakura, H.; Nagashima, M.; Yoshimura, K.; Ito, J.; Kimura, I.; Uriu, K.; Kosugi, Y.; Suganami, M.; Oide, A.; Yokoyama, M.; Chiba, M.; Saito, A.; Butlertanaka, E.P.; Tanaka, Y.L.; Ikeda, T.; Motozono, C.; Nasser, H.; Shimizu, R.; Yuan, Y.; Kitazato, K.; Hasebe, H.; Nakagawa, S.; Wu, J.; Takahashi, M.; Fukuhara, T.; Shimizu, K.; Tsushima, K.; Kubo, H.; Shirakawa, K.; Kazuma, Y.; Nomura, R.; Horisawa, Y.; Takaori-Kondo, A.; Tokunaga, K.; Ozono, S.; Baker, S.; Dougan, G.; Hess, C.; Kingston, N.; Lehner, P.J.; Lyons, P.A.; Matheson, N.J.; Owehand, W.H.; Saunders, C.; Summers, C.; Thaventhiran, J.E.D.; Toshner, M.; Weekes, M.P.; Maxwell, P.; Shaw, A.; Bucke, A.; Calder, J.; Canna, L.; Domingo, J.; Elmer, A.; Fuller, S.; Harris, J.; Hewitt, S.; Kennet, J.; Jose, S.; Kourampa, J.; Meadows, A.; O'Brien, C.; Price, J.; Publico, C.; Rastall, R.; Ribeiro, C.; Rowlands, J.; Ruffolo, V.; Tordesillas, H.; Bullman, B.; Dunmore, B.J.; Fawke, S.; Graf, S.; Hodgson, J.; Huang, C.; Hunter, K.; Jones, E.; Legchenko, E.; Matara, C.; Martin, J.; Mescia, F.; O'Donnell, C.; Pointon, L.; Pond, N.; Shih, J.; Sutcliffe, R.; Tilly, T.; Treacy, C.; Tong, Z.; Wood, J.; Wylot, M.; Bergamaschi, L.; Betancourt, A.; Bower, G.; Cossetti, C.; De Sa, A.; Epping, M.; Fawke, S.; Gleadall, N.; Grenfell, R.; Hinch, A.; Huhn, O.; Jackson, S.; Jarvis, I.; Krishna, B.; Lewis, D.; Marsden, J.; Nice, F.; Okecha, G.; Omarjee, O.; Perera, M.; Potts, M.; Richoz, N.; Romashova, V.; Yarkoni, N.S.; Sharma, R.; Stefanucci, L.; Stephens, J.; Strezlecki, M.; Turner, L.; De Bie, E.M.D.D.; Bunclark, K.; Josipovic, M.; Mackay, M.; Rossi, S.; Selvan, M.; Spencer, S.; Yong, C.; Allison, J.; Butcher, H.; Caputo, D.; Clapham-Riley, D.; Dewhurst, E.; Furlong, A.; Graves, B.; Gray, J.; Ivers, T.; Kasanicki, M.; Le Gresley, E.; Linger, R.; Meloy, S.; Muldoon, F.; Ovington, N.; Papadia, S.; Phelan, I.; Stark, H.; Stirrups, K.E.; Townsend, P.; Walker, N.; Webster, J.; Scholtes, I.; Hein, S.; King, R.; Mavousian, A.; Lee, J.H.; Bassi, J.; Silacci-Fegni, C.; Saliba, C.; Pinto, D.; Irie, T.; Yoshida, I.; Hamilton, W.L.; Sato, K.; Bhatt, S.; Flaxman, S.; James, L.C.; Corti, D.; Piccoli, L.; Barclay, W.S.; Rakshit, P.; Agrawal, A.; Gupta, R.K.

doi:10.1038/s41586-021-03944-y

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.

SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion / P. Mlcochova, S.A. Kemp, M.S. Dhar, G. Papa, B. Meng, I.A.T.M. Ferreira, R. Datir, D.A. Collier, A. Albecka, S. Singh, R. Pandey, J. Brown, J. Zhou, N. Goonawardane, S. Mishra, C. Whittaker, T. Mellan, R. Marwal, M. Datta, S. Sengupta, K. Ponnusamy, V.S. Radhakrishnan, A. Abdullahi, O. Charles, P. Chattopadhyay, P. Devi, D. Caputo, T. Peacock, C. Wattal, N. Goel, A. Satwik, R. Vaishya, M. Agarwal, H. Chauhan, T. Dikid, H. Gogia, H. Lall, K. Verma, M.S. Dhar, M.K. Singh, N. Soni, N. Meena, P. Madan, P. Singh, R. Sharma, R. Sharma, S. Kabra, S. Kumar, S. Kumari, U. Sharma, U. Chaudhary, S. Sivasubbu, V. Scaria, J.K. Oberoi, R. Raveendran, S. Datta, S. Das, A. Maitra, S. Chinnaswamy, N.K. Biswas, A. Parida, S.K. Raghav, P. Prasad, A. Sarin, S. Mayor, U. Ramakrishnan, D. Palakodeti, A.S.N. Seshasayee, K. Thangaraj, M.D. Bashyam, A. Dalal, M. Bhat, Y. Shouche, A. Pillai, P. Abraham, V.A. Potdar, S.S. Cherian, A.S. Desai, C. Pattabiraman, M.V. Manjunatha, R.S. Mani, G.A. Udupi, V. Nandicoori, K.B. Tallapaka, D.T. Sowpati, R. Kawabata, N. Morizako, K. Sadamasu, H. Asakura, M. Nagashima, K. Yoshimura, J. Ito, I. Kimura, K. Uriu, Y. Kosugi, M. Suganami, A. Oide, M. Yokoyama, M. Chiba, A. Saito, E.P. Butlertanaka, Y.L. Tanaka, T. Ikeda, C. Motozono, H. Nasser, R. Shimizu, Y. Yuan, K. Kitazato, H. Hasebe, S. Nakagawa, J. Wu, M. Takahashi, T. Fukuhara, K. Shimizu, K. Tsushima, H. Kubo, K. Shirakawa, Y. Kazuma, R. Nomura, Y. Horisawa, A. Takaori-Kondo, K. Tokunaga, S. Ozono, S. Baker, G. Dougan, C. Hess, N. Kingston, P.J. Lehner, P.A. Lyons, N.J. Matheson, W.H. Owehand, C. Saunders, C. Summers, J.E.D. Thaventhiran, M. Toshner, M.P. Weekes, P. Maxwell, A. Shaw, A. Bucke, J. Calder, L. Canna, J. Domingo, A. Elmer, S. Fuller, J. Harris, S. Hewitt, J. Kennet, S. Jose, J. Kourampa, A. Meadows, C. O'Brien, J. Price, C. Publico, R. Rastall, C. Ribeiro, J. Rowlands, V. Ruffolo, H. Tordesillas, B. Bullman, B.J. Dunmore, S. Fawke, S. Graf, J. Hodgson, C. Huang, K. Hunter, E. Jones, E. Legchenko, C. Matara, J. Martin, F. Mescia, C. O'Donnell, L. Pointon, N. Pond, J. Shih, R. Sutcliffe, T. Tilly, C. Treacy, Z. Tong, J. Wood, M. Wylot, L. Bergamaschi, A. Betancourt, G. Bower, C. Cossetti, A. De Sa, M. Epping, S. Fawke, N. Gleadall, R. Grenfell, A. Hinch, O. Huhn, S. Jackson, I. Jarvis, B. Krishna, D. Lewis, J. Marsden, F. Nice, G. Okecha, O. Omarjee, M. Perera, M. Potts, N. Richoz, V. Romashova, N.S. Yarkoni, R. Sharma, L. Stefanucci, J. Stephens, M. Strezlecki, L. Turner, E.M.D.D. De Bie, K. Bunclark, M. Josipovic, M. Mackay, S. Rossi, M. Selvan, S. Spencer, C. Yong, J. Allison, H. Butcher, D. Caputo, D. Clapham-Riley, E. Dewhurst, A. Furlong, B. Graves, J. Gray, T. Ivers, M. Kasanicki, E. Le Gresley, R. Linger, S. Meloy, F. Muldoon, N. Ovington, S. Papadia, I. Phelan, H. Stark, K.E. Stirrups, P. Townsend, N. Walker, J. Webster, I. Scholtes, S. Hein, R. King, A. Mavousian, J.H. Lee, J. Bassi, C. Silacci-Fegni, C. Saliba, D. Pinto, T. Irie, I. Yoshida, W.L. Hamilton, K. Sato, S. Bhatt, S. Flaxman, L.C. James, D. Corti, L. Piccoli, W.S. Barclay, P. Rakshit, A. Agrawal, R.K. Gupta. - In: NATURE. - ISSN 0028-0836. - 599:7883(2021), pp. 114-119. [10.1038/s41586-021-03944-y]

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

Mlcochova P.;Kemp S. A.;Dhar M. S.;G. Papa;Meng B.;Ferreira I. A. T. M.;Datir R.;Collier D. A.;Albecka A.;Singh S.;Pandey R.;Brown J.;Zhou J.;Goonawardane N.;Mishra S.;Whittaker C.;Mellan T.;Marwal R.;Datta M.;Sengupta S.;Ponnusamy K.;Radhakrishnan V. S.;Abdullahi A.;Charles O.;Chattopadhyay P.;Devi P.;Caputo D.;Peacock T.;Wattal C.;Goel N.;Satwik A.;Vaishya R.;Agarwal M.;Chauhan H.;Dikid T.;Gogia H.;Lall H.;Verma K.;Dhar M. S.;Singh M. K.;Soni N.;Meena N.;Madan P.;Singh P.;Sharma R.;Sharma R.;Kabra S.;Kumar S.;Kumari S.;Sharma U.;Chaudhary U.;Sivasubbu S.;Scaria V.;Oberoi J. K.;Raveendran R.;Datta S.;Das S.;Maitra A.;Chinnaswamy S.;Biswas N. K.;Parida A.;Raghav S. K.;Prasad P.;Sarin A.;Mayor S.;Ramakrishnan U.;Palakodeti D.;Seshasayee A. S. N.;Thangaraj K.;Bashyam M. D.;Dalal A.;Bhat M.;Shouche Y.;Pillai A.;Abraham P.;Potdar V. A.;Cherian S. S.;Desai A. S.;Pattabiraman C.;Manjunatha M. V.;Mani R. S.;Udupi G. A.;Nandicoori V.;Tallapaka K. B.;Sowpati D. T.;Kawabata R.;Morizako N.;Sadamasu K.;Asakura H.;Nagashima M.;Yoshimura K.;Ito J.;Kimura I.;Uriu K.;Kosugi Y.;Suganami M.;Oide A.;Yokoyama M.;Chiba M.;Saito A.;Butlertanaka E. P.;Tanaka Y. L.;Ikeda T.;Motozono C.;Nasser H.;Shimizu R.;Yuan Y.;Kitazato K.;Hasebe H.;Nakagawa S.;Wu J.;Takahashi M.;Fukuhara T.;Shimizu K.;Tsushima K.;Kubo H.;Shirakawa K.;Kazuma Y.;Nomura R.;Horisawa Y.;Takaori-Kondo A.;Tokunaga K.;Ozono S.;Baker S.;Dougan G.;Hess C.;Kingston N.;Lehner P. J.;Lyons P. A.;Matheson N. J.;Owehand W. H.;Saunders C.;Summers C.;Thaventhiran J. E. D.;Toshner M.;Weekes M. P.;Maxwell P.;Shaw A.;Bucke A.;Calder J.;Canna L.;Domingo J.;Elmer A.;Fuller S.;Harris J.;Hewitt S.;Kennet J.;Jose S.;Kourampa J.;Meadows A.;O'Brien C.;Price J.;Publico C.;Rastall R.;Ribeiro C.;Rowlands J.;Ruffolo V.;Tordesillas H.;Bullman B.;Dunmore B. J.;Fawke S.;Graf S.;Hodgson J.;Huang C.;Hunter K.;Jones E.;Legchenko E.;Matara C.;Martin J.;Mescia F.;O'Donnell C.;Pointon L.;Pond N.;Shih J.;Sutcliffe R.;Tilly T.;Treacy C.;Tong Z.;Wood J.;Wylot M.;Bergamaschi L.;Betancourt A.;Bower G.;Cossetti C.;De Sa A.;Epping M.;Fawke S.;Gleadall N.;Grenfell R.;Hinch A.;Huhn O.;Jackson S.;Jarvis I.;Krishna B.;Lewis D.;Marsden J.;Nice F.;Okecha G.;Omarjee O.;Perera M.;Potts M.;Richoz N.;Romashova V.;Yarkoni N. S.;Sharma R.;Stefanucci L.;Stephens J.;Strezlecki M.;Turner L.;De Bie E. M. D. D.;Bunclark K.;Josipovic M.;Mackay M.;Rossi S.;Selvan M.;Spencer S.;Yong C.;Allison J.;Butcher H.;Caputo D.;Clapham-Riley D.;Dewhurst E.;Furlong A.;Graves B.;Gray J.;Ivers T.;Kasanicki M.;Le Gresley E.;Linger R.;Meloy S.;Muldoon F.;Ovington N.;Papadia S.;Phelan I.;Stark H.;Stirrups K. E.;Townsend P.;Walker N.;Webster J.;Scholtes I.;Hein S.;King R.;Mavousian A.;Lee J. H.;Bassi J.;Silacci-Fegni C.;Saliba C.;Pinto D.;Irie T.;Yoshida I.;Hamilton W. L.;Sato K.;Bhatt S.;Flaxman S.;James L. C.;Corti D.;Piccoli L.;Barclay W. S.;Rakshit P.;Agrawal A.;Gupta R. K.

2021

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.

Scheda breve

Scheda completa

Scheda completa (DC)

	Settori scientifico-disciplinari dell'articolo (validi dal 09/05/2024)
	
				Settore BIOS-15/A - Microbiologia
Settore MEDS-03/A - Microbiologia e microbiologia clinica
Settore BIOS-08/A - Biologia molecolare
			
	Titolo del progetto
	
	Titolo Progetto
	
									Spatiotemporal statistical machine learning (ST-SML): theory, methods, and applications
								
	Nome finanziatore
	
										UK Research and Innovation
									
	Finanziamento
	
									EPSRC
								
	N. Contratto
	
									EP/V002910/1
								
	Titolo Progetto
	
									G2P-UK; A National Virology Consortium to address phenotypic consequences of SARSCoV-2 genomic variation
								
	Nome finanziatore
	
										UK Research and Innovation
									
	Finanziamento
	
									MRC
								
	N. Contratto
	
									MR/W005611/1
								
	Data di pubblicazione
	
				2021
			
	Rivista in ANCE
	
				NATURE
			
	DOI
	
				https://dx.doi.org/10.1038/s41586-021-03944-y
			
	Tipologia
	
				Article (author)
			
	Appare nelle tipologie:
	
				01 - Articolo su periodico

File in questo prodotto:

File	Dimensione	Formato
unpaywall-bitstream - 1568970161_compressed.pdf accesso aperto Tipologia: Publisher's version/PDF Licenza: Creative commons Dimensione 1.18 MB Formato Adobe PDF Visualizza/Apri	1.18 MB	Adobe PDF	Visualizza/Apri

Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/1219238

Citazioni

ND

1035

895

1413

IRIS Institutional Research Information System - AIR Archivio Istituzionale della Ricerca