Browsing by Author "Worlock K.B."

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    Correction to: Human SARS-CoV-2 challenge uncovers local and systemic response dynamics (Nature, (2024), 631, 8019, (189-198), 10.1038/s41586-024-07575-x)
    (2024-01-01) Lindeboom R.G.H.; Worlock K.B.; Dratva L.M.; Yoshida M.; Scobie D.; Wagstaffe H.R.; Richardson L.; Wilbrey-Clark A.; Barnes J.L.; Kretschmer L.; Polanski K.; Allen-Hyttinen J.; Mehta P.; Sumanaweera D.; Boccacino J.M.; Sungnak W.; Elmentaite R.; Huang N.; Mamanova L.; Kapuge R.; Bolt L.; Prigmore E.; Killingley B.; Kalinova M.; Mayer M.; Boyers A.; Mann A.; Swadling L.; Woodall M.N.J.; Ellis S.; Smith C.M.; Teixeira V.H.; Janes S.M.; Chambers R.C.; Haniffa M.; Catchpole A.; Heyderman R.; Noursadeghi M.; Chain B.; Mayer A.; Meyer K.B.; Chiu C.; Nikolić M.Z.; Teichmann S.A.; Lindeboom R.G.H.; Mahidol University
    Correction to: Naturehttps://doi.org/10.1038/s41586-024-07575-x Published online 19 June 2024 In the version of the article initially published, the Acknowledgements was missing the following text, which has now been added to the HTML and PDF versions of the article: “The authors gratefully acknowledge support from the UK Vaccine Taskforce of the Department of Business, Energy and Industrial Strategy of Her Majesty’s Government (BEIS). We thank the following organizations for their invaluable contributions to development and implementation of the SARS-CoV-2 human challenge project: the Royal Free London NHS Foundation Trust, Human Infection Challenge Network for Vaccine Development (HIC-Vac), NIHR Clinical Research Network staff at the Royal Bolton Hospital, and ISARIC4C Investigators (https://isaric4c.net/about/authors/) for providing the clinical material for challenge virus production. C.C. is supported by the NIHR Imperial Biomedical Research Centre (BRC) award to Imperial College Healthcare NHS Trust and Imperial College London. ISARIC4C is funded by the National Institute for Health Research (NIHR; award CO-CIN-01), the Medical Research Council (MRC; grant MC_PC_19059), the NIHR Health Protection Research Unit in Emerging and Zoonotic Infections at University of Liverpool in partnership with Public Health England (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford (NIHR award 200907), Liverpool Experimental Cancer Medicine Centre provided infrastructure support for this research (grant reference C18616/A25153) and NIHR Health Protection Research Unit in Respiratory Infections (NIHR award 200927). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, DHSC or BEIS.”
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    Human SARS-CoV-2 challenge uncovers local and systemic response dynamics
    (2024-01-01) Lindeboom R.G.H.; Worlock K.B.; Dratva L.M.; Yoshida M.; Scobie D.; Wagstaffe H.R.; Richardson L.; Wilbrey-Clark A.; Barnes J.L.; Kretschmer L.; Polanski K.; Allen-Hyttinen J.; Mehta P.; Sumanaweera D.; Boccacino J.M.; Sungnak W.; Elmentaite R.; Huang N.; Mamanova L.; Kapuge R.; Bolt L.; Prigmore E.; Killingley B.; Kalinova M.; Mayer M.; Boyers A.; Mann A.; Swadling L.; Woodall M.N.J.; Ellis S.; Smith C.M.; Teixeira V.H.; Janes S.M.; Chambers R.C.; Haniffa M.; Catchpole A.; Heyderman R.; Noursadeghi M.; Chain B.; Mayer A.; Meyer K.B.; Chiu C.; Nikolić M.Z.; Teichmann S.A.; Lindeboom R.G.H.; Mahidol University
    The COVID-19 pandemic is an ongoing global health threat, yet our understanding of the dynamics of early cellular responses to this disease remains limited1. Here in our SARS-CoV-2 human challenge study, we used single-cell multi-omics profiling of nasopharyngeal swabs and blood to temporally resolve abortive, transient and sustained infections in seronegative individuals challenged with pre-Alpha SARS-CoV-2. Our analyses revealed rapid changes in cell-type proportions and dozens of highly dynamic cellular response states in epithelial and immune cells associated with specific time points and infection status. We observed that the interferon response in blood preceded the nasopharyngeal response. Moreover, nasopharyngeal immune infiltration occurred early in samples from individuals with only transient infection and later in samples from individuals with sustained infection. High expression of HLA-DQA2 before inoculation was associated with preventing sustained infection. Ciliated cells showed multiple immune responses and were most permissive for viral replication, whereas nasopharyngeal T cells and macrophages were infected non-productively. We resolved 54 T cell states, including acutely activated T cells that clonally expanded while carrying convergent SARS-CoV-2 motifs. Our new computational pipeline Cell2TCR identifies activated antigen-responding T cells based on a gene expression signature and clusters these into clonotype groups and motifs. Overall, our detailed time series data can serve as a Rosetta stone for epithelial and immune cell responses and reveals early dynamic responses associated with protection against infection.