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

Abstract

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.

Metadata

Item Type:	Article
Authors/Creators:	Tomic, A Skelly, DT Ogbe, A O’Connor, D Pace, M Adland, E Alexander, F Ali, M Allott, K Azim Ansari, M Belij-Rammerstorfer, S Bibi, S Blackwell, L Brown, A Brown, H Cavell, B Clutterbuck, EA de Silva, T https://orcid.org/0000-0002-6498-9212 Eyre, D Lumley, S Flaxman, A Grist, J Hackstein, C-P Halkerston, R Harding, AC Hill, J James, T Jay, C Johnson, SA Kronsteiner, B Lie, Y Linder, A Longet, S Marinou, S Matthews, PC Mellors, J Petropoulos, C Rongkard, P Sedik, C Silva-Reyes, L Smith, H Stockdale, L Taylor, S Thomas, S Tipoe, T Turtle, L Vieira, VA Wrin, T Stafford, L Abuelgasim, H Alhussni, A Arancibia-Cárcamo, CV Borak, M Cutteridge, J Deeks, A Denly, L Dimitriadis, S Fassih, S Foord, T Fordwoh, T Holmes, J Horsington, B Kerneis, S Kim, D Lillie, K Morrow, J O’Donnell, D Ritter, TG Simmons, B Taylor, A Thomas, SR Warren, Y Watson, AJR Weeks, E Wilson, R Young, R Duncan, CJA Moore, SC Payne, R Richter, A Rowland-Jones, S Mentzer, AJ Cassar, MP Dong, T Fries, A Gilbert-Jaramillo, J Ho, L-P Knight, JC Neubauer, S Peng, Y Petousi, N Raman, B Talbot, NP Pollard, AJ Lambe, T Conlon, CP Jeffery, K Travis, S Goulder, P Frater, J Mentzer, AJ Stafford, L Carroll, MW James, WS Klenerman, P Barnes, E Dold, C Dunachie, SJ
Copyright, Publisher and Additional Information:	© The Author(s) 2022. 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/.
Keywords:	Immunological memory; Infection; SARS-CoV-2; Viral infection
Dates:	Published: 10 March 2022 Published (online): 10 March 2022 Accepted: 17 February 2022
Institution:	The University of Sheffield
Academic Units:	The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > Department of Infection and Immunity (Sheffield)
Depositing User:	Symplectic Sheffield
Date Deposited:	14 Mar 2022 14:38
Last Modified:	14 Mar 2022 14:38
Status:	Published
Publisher:	Nature Research (part of Springer Nature)
Refereed:	Yes
Identification Number:	10.1038/s41467-022-28898-1
Related URLs:	Dataset
Open Archives Initiative ID (OAI ID):	oai:eprints.whiterose.ac.uk:184702