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

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      1 , 2 , 1 , 2 , 3 , 4 , 5 , 1 , 2 , 1 , 2 , 1 , 2 , 2 , 3 , 5 , 4 , 6 , 7 , 7 , 7 , 8 , 8 , 8 , 4 , 4 , 6 , 4 , 4 , 1 , 2 , 3 , 6 , 6 , 9 , 8 , 10 , 10 , 10 , 11 , 12 , The Indian SARS-CoV-2 Genomics Consortium (INSACOG), The Genotype to Phenotype Japan (G2P-Japan) Consortium, The CITIID-NIHR BioResource COVID-19 Collaboration, 13 , 13 , 14 , 15 , 15 , 15 , 15 , 16 , 17 , 2 , 18 , 19 , 4 , 20 , 21 , 5 , 15 , 15 , 8 , 4 , , 6 , , 1 , 2 , 22 ,
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      Nature Publishing Group UK
      Infection, SARS-CoV-2

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          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.

          Abstract

          A study of SARS-CoV-2 variants examining their transmission, infectivity, and potential resistance to therapies provides insights into the biology of the Delta variant and its role in the global pandemic.

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          Most cited references34

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          MAFFT Multiple Sequence Alignment Software Version 7: Improvements in Performance and Usability

          We report a major update of the MAFFT multiple sequence alignment program. This version has several new features, including options for adding unaligned sequences into an existing alignment, adjustment of direction in nucleotide alignment, constrained alignment and parallel processing, which were implemented after the previous major update. This report shows actual examples to explain how these features work, alone and in combination. Some examples incorrectly aligned by MAFFT are also shown to clarify its limitations. We discuss how to avoid misalignments, and our ongoing efforts to overcome such limitations.
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            Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR

            Background The ongoing outbreak of the recently emerged novel coronavirus (2019-nCoV) poses a challenge for public health laboratories as virus isolates are unavailable while there is growing evidence that the outbreak is more widespread than initially thought, and international spread through travellers does already occur. Aim We aimed to develop and deploy robust diagnostic methodology for use in public health laboratory settings without having virus material available. Methods Here we present a validated diagnostic workflow for 2019-nCoV, its design relying on close genetic relatedness of 2019-nCoV with SARS coronavirus, making use of synthetic nucleic acid technology. Results The workflow reliably detects 2019-nCoV, and further discriminates 2019-nCoV from SARS-CoV. Through coordination between academic and public laboratories, we confirmed assay exclusivity based on 297 original clinical specimens containing a full spectrum of human respiratory viruses. Control material is made available through European Virus Archive – Global (EVAg), a European Union infrastructure project. Conclusion The present study demonstrates the enormous response capacity achieved through coordination of academic and public laboratories in national and European research networks.
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              Effectiveness of Covid-19 Vaccines against the B.1.617.2 (Delta) Variant

              Background The B.1.617.2 (delta) variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (Covid-19), has contributed to a surge in cases in India and has now been detected across the globe, including a notable increase in cases in the United Kingdom. The effectiveness of the BNT162b2 and ChAdOx1 nCoV-19 vaccines against this variant has been unclear. Methods We used a test-negative case–control design to estimate the effectiveness of vaccination against symptomatic disease caused by the delta variant or the predominant strain (B.1.1.7, or alpha variant) over the period that the delta variant began circulating. Variants were identified with the use of sequencing and on the basis of the spike ( S ) gene status. Data on all symptomatic sequenced cases of Covid-19 in England were used to estimate the proportion of cases with either variant according to the patients’ vaccination status. Results Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) was notably lower among persons with the delta variant (30.7%; 95% confidence interval [CI], 25.2 to 35.7) than among those with the alpha variant (48.7%; 95% CI, 45.5 to 51.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 93.7% (95% CI, 91.6 to 95.3) among persons with the alpha variant and 88.0% (95% CI, 85.3 to 90.1) among those with the delta variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 74.5% (95% CI, 68.4 to 79.4) among persons with the alpha variant and 67.0% (95% CI, 61.3 to 71.8) among those with the delta variant. Conclusions Only modest differences in vaccine effectiveness were noted with the delta variant as compared with the alpha variant after the receipt of two vaccine doses. Absolute differences in vaccine effectiveness were more marked after the receipt of the first dose. This finding would support efforts to maximize vaccine uptake with two doses among vulnerable populations. (Funded by Public Health England.)
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                Author and article information

                Contributors
                partho_rakshit@yahoo.com
                a.agrawal@igib.in
                rkg20@cam.ac.uk
                Journal
                Nature
                Nature
                Nature
                Nature Publishing Group UK (London )
                0028-0836
                1476-4687
                6 September 2021
                6 September 2021
                2021
                : 599
                : 7883
                : 114-119
                Affiliations
                [1 ]Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Cambridge, UK
                [2 ]GRID grid.5335.0, ISNI 0000000121885934, Department of Medicine, , University of Cambridge, ; Cambridge, UK
                [3 ]GRID grid.83440.3b, ISNI 0000000121901201, University College London, ; London, UK
                [4 ]GRID grid.419568.7, ISNI 0000 0001 0086 9601, National Centre for Disease Control, ; Delhi, India
                [5 ]GRID grid.42475.30, ISNI 0000 0004 0605 769X, MRC – Laboratory of Molecular Biology, ; Cambridge, UK
                [6 ]GRID grid.417639.e, CSIR Institute of Genomics and Integrative Biology, ; Delhi, India
                [7 ]GRID grid.7445.2, ISNI 0000 0001 2113 8111, Department of Infectious Diseases, , Imperial College London, ; London, UK
                [8 ]GRID grid.7445.2, ISNI 0000 0001 2113 8111, Medical Research Council (MRC) Centre for Global Infectious Disease Analysis, Jameel Institute, School of Public Health, , Imperial College London, ; London, UK
                [9 ]NIHR Bioresource, Cambridge, UK
                [10 ]Sri Ganga Ram Hospital, New Delhi, India
                [11 ]GRID grid.414612.4, ISNI 0000 0004 1804 700X, Indraprastha Apollo Hospital, ; New Delhi, India
                [12 ]Northern Railway Central Hospital, New Delhi, India
                [13 ]GRID grid.449973.4, ISNI 0000 0004 0612 0791, Wellcome-MRC Cambridge Stem Cell Institute, ; Cambridge, UK
                [14 ]GRID grid.5335.0, ISNI 0000000121885934, Department of Physiology, Development and Neuroscience, , University of Cambridge, ; Cambridge, UK
                [15 ]GRID grid.498378.9, Humabs Biomed SA, a subsidiary of Vir Biotechnology, ; Bellinzona, Switzerland
                [16 ]GRID grid.257022.0, ISNI 0000 0000 8711 3200, Institute of Biomedical and Health Sciences, , Hiroshima University, ; Hiroshima, Japan
                [17 ]GRID grid.417096.d, Tokyo Metropolitan Institute of Public Health, ; Tokyo, Japan
                [18 ]GRID grid.26999.3d, ISNI 0000 0001 2151 536X, Division of Systems Virology, The Institute of Medical Science, , The University of Tokyo, ; Tokyo, Japan
                [19 ]GRID grid.419082.6, ISNI 0000 0004 1754 9200, CREST, Japan Science and Technology Agency, ; Saitama, Japan
                [20 ]GRID grid.5254.6, ISNI 0000 0001 0674 042X, Section of Epidemiology, Department of Public Health, , University of Copenhagen, ; Copenhagen, Denmark
                [21 ]GRID grid.4991.5, ISNI 0000 0004 1936 8948, Department of Computer Science, , University of Oxford, ; Oxford, UK
                [22 ]GRID grid.488675.0, Africa Health Research Institute, ; Durban, South Africa
                [23 ]GRID grid.410872.8, ISNI 0000 0004 1774 5690, National Institute of Biomedical Genomics, ; Kalyani, India
                [24 ]GRID grid.418782.0, ISNI 0000 0004 0504 0781, Institute of Life Sciences (ILS), ; Bhubaneswar, India
                [25 ]GRID grid.510243.1, ISNI 0000 0004 0501 1024, InSTEM/ NCBS, ; Bangalore, India
                [26 ]GRID grid.145749.a, ISNI 0000 0004 1767 2735, Centre for DNA Fingerprinting and Diagnostics, ; Hyderabad, India
                [27 ]GRID grid.419235.8, National Centre for Cell Science, ; Pune, India
                [28 ]GRID grid.419672.f, ISNI 0000 0004 1767 073X, National Institute of Virology, ; Pune, India
                [29 ]GRID grid.416861.c, ISNI 0000 0001 1516 2246, National Institute of Mental Health and Neuroscience, ; Bangalore, India
                [30 ]GRID grid.417634.3, ISNI 0000 0004 0496 8123, Centre for Cellular and Molecular Biology, ; Hyderabad, India
                [31 ]GRID grid.410849.0, ISNI 0000 0001 0657 3887, University of Miyazaki, ; Miyazaki, Japan
                [32 ]GRID grid.274841.c, ISNI 0000 0001 0660 6749, Kumamoto University, ; Kumamoto, Japan
                [33 ]GRID grid.265061.6, ISNI 0000 0001 1516 6626, Tokai University, ; Tokyo, Japan
                [34 ]GRID grid.39158.36, ISNI 0000 0001 2173 7691, Hokkaido University, ; Sapporo, Japan
                [35 ]GRID grid.258799.8, ISNI 0000 0004 0372 2033, Kyoto University, ; Kyoto, Japan
                [36 ]GRID grid.410795.e, ISNI 0000 0001 2220 1880, National Institute of Infectious Diseases, ; Tokyo, Japan
                [37 ]GRID grid.24029.3d, ISNI 0000 0004 0383 8386, Cambridge University Hospitals NHS Trust, ; Cambridge, UK
                [38 ]GRID grid.120073.7, ISNI 0000 0004 0622 5016, Cambridge Clinical Research Centre, NIHR Clinical Research Facility, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke’s Hospital, ; Cambridge, UK
                [39 ]GRID grid.5335.0, ISNI 0000000121885934, Department of Biochemistry, , University of Cambridge, ; Cambridge, UK
                [40 ]GRID grid.5335.0, ISNI 0000000121885934, University of Cambridge, Cambridge Biomedical Campus, ; Cambridge, UK
                Author information
                http://orcid.org/0000-0001-9751-1808
                Article
                3944
                10.1038/s41586-021-03944-y
                8566220
                34488225
                797d96da-af2d-4b3e-8b7d-eb8a662d0b24
                © The Author(s) 2021

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 18 June 2021
                : 23 August 2021
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