Divergent trajectories of antiviral memory after SARS-CoV-2 infection

OPTIC Clinical Group, PITCH Study Group, C-MORE Group, Adriana Tomic, Donal T. Skelly, Ane Ogbe, Daniel O'Connor, Matthew Pace, Emily Adland, Frances Alexander, Mohammad Ali, Kirk Allott, M. Azim Ansari, Sandra Belij-Rammerstorfer, Sagida Bibi, Luke Blackwell, Anthony Brown, Helen Brown, Breeze Cavell, Elizabeth A. ClutterbuckThushan de Silva, David Eyre, Sheila Lumley, Amy Flaxman, James Grist, Carl Philipp Hackstein, Rachel Halkerston, Adam C. Harding, Jennifer Hill, Tim James, Cecilia Jay, Síle A. Johnson, Barbara Kronsteiner, Yolanda Lie, Aline Linder, Stephanie Longet, Spyridoula Marinou, Philippa C. Matthews, Jack Mellors, Christos Petropoulos, Patpong Rongkard, Cynthia Sedik, Laura Silva-Reyes, Holly Smith, Lisa Stockdale, Stephen Taylor, Stephen Thomas, Timothy Tipoe, Lance Turtle, Vinicius Adriano Vieira, Terri Wrin, Andrew J. Pollard, Miles W. Carroll

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The trajectories of acquired immunity to severe acute respiratory syndrome coronavirus 2 infection are not fully understood. We present a detailed longitudinal cohort study of UK healthcare workers prior to vaccination, presenting April-June 2020 with asymptomatic or symptomatic infection. Here we show a highly variable range of responses, some of which (T cell interferon-gamma ELISpot, N-specific antibody) wane over time, while others (spike-specific antibody, B cell memory ELISpot) are stable. We use integrative analysis and a machine-learning approach (SIMON - Sequential Iterative Modeling OverNight) to explore this heterogeneity. We identify a subgroup of participants with higher antibody responses and interferon-gamma ELISpot T cell responses, and a robust trajectory for longer term immunity associates with higher levels of neutralising antibodies against the infecting (Victoria) strain and also against variants B.1.1.7 (alpha) and B.1.351 (beta). These variable trajectories following early priming may define subsequent protection from severe disease from novel variants.

Original languageEnglish
Article number1251
Number of pages20
JournalNature Communications
Issue number1
Publication statusPublished - 10 Mar 2022

Bibliographical note

Funding Information: The authors wish to thank all the healthcare worker volunteers who participated in this study, and Suki Kenth for administrative support. This work was funded by the UK Department of Health and Social Care as part of the PITCH (Protective Immunity from T cells to Covid-19 in Health workers) Consortium, with contributions from UKRI/NIHR through the UK Coronavirus Immunology Consortium (UK-CIC), the Huo Family Foundation and The National Institute for Health Research (UKRIDHSC COVID-19 Rapid Response Rolling Call, Grant Reference Number COV19-RECPLAS). AT is supported by the EU’s Horizon2020 Marie Sklodowska-Curie Fellowship (FluPRINT, grant number 796636). DS is supported by the NIHR Academic Clinical Fellow programme in Oxford. M.A.A. is supported by a Wellcome Trust Sir Henry Dale Fellowship (220171/Z/20/Z). D.W.E. is a Robertson Foundation Fellow. P.C.M. is funded by a Wellcome intermediate fellowship, ref. 110110/Z/15/Z. L.T. is supported by the Wellcome Trust (grant number 205228/Z/16/Z) and the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Emerging and Zoonotic Infections (NIHR200907) at University of Liverpool in partnership with Public Health England (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford. P.K. and E.B. are NIHR Senior Investigators and PK is funded by WT109965MA. S.J.D. is funded by an NIHR Global Research Professorship (NIHR300791).

The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, the Department of Health and Social Care or Public Health England. The graphic in Fig. 6a has been created with Servier Medical Art images (smart.servier.com). Servier Medical Art by Servier is licensed under a Creative Commons Attribution 3.0 Unported License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided that the original work is properly cited.

D.W.E. declares lecture fees from Gilead, outside the submitted work. No other competing interests declared. S.J.D. is a Scientific Advisor to the Scottish Parliament, for which a fee is received. All other authors declare no other competing interests.

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/.

Publisher Copyright: © The Author(s) 2022

Citation: Tomic, A., Skelly, D.T., Ogbe, A. et al. Divergent trajectories of antiviral memory after SARS-CoV-2 infection. Nat Commun 13, 1251 (2022).

DOI: https://doi.org/10.1038/s41467-022-28898-1




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