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

Adriana Tomić ,Amy Flaxman ,Christina Dold ,Nayia Petousi ,Terri Wrin ,Adam Harding ,Julian C Knight ,Jennifer Holmes ,Sandra Belij‐Rammerstorfer ,Christos J Petropoulos ,Cynthia Sedik ,Ahmed Alhussni ,Lance Turtle ,Joseph Cutteridge ,Ling-Pei Ho ,Alex Richter ,Thomas Fordwoh ,Philippa C Matthews ,Robert L Wilson ,Stefan Neubauer ,A Taylor ,Paul Klenerman ,Donal Skelly ,Yolanda Warren ,Beatrice Simmons ,Daniel O’connor ,Ane Ogbe ,David Kim ,Sarah Thomas ,Tao Dong ,Philip Goulder ,Carl-Philipp Hackstein ,Jack Mellors ,Frances Alexander ,Thushan I De Silva ,John Frater ,Yanchun Peng ,Hibatullah Abuelgasim ,Thomas Foord ,Vinícius Vieira ,Mohammad Ali ,Alexander J Mentzer ,Christopher P Conlon ,Katy Lillie ,Síle A Johnson ,Martyna Borak ,Jordan Morrow ,Breeze E Cavell ,Emily Adland ,Sheila F Lumley ,Stephanie Longet ,Rebecca P Payne ,Matthew Pace ,Jennifer Hill ,William James ,Carolina V Arancibia‐Cárcamo ,Holly Smith ,Tim James ,Bryn Horsington ,Alexandra Deeks ,Elizabeth A Clutterbuck ,Katie Jeffery ,Anthony Brown ,Stavros I Dimitriadis ,Nick P Talbot ,Sagida Bibi ,Lucy Denly ,David W Eyre ,Spyridoula Marinou ,Anastasia Fries ,Eleanor Barnes ,M Azim Ansari ,Cecilia Jay ,Sarah Rowland‐Jones ,Betty Raman ,Javier Gilbert‐Jaramillo ,Andrew J Pollard ,Aline Linder ,Thomas G Ritter ,Adam Watson ,Kirk Allott ,Barbara Kronsteiner ,Simon Travis ,Shayan Fassih ,Lisa Stockdale ,Mark Philip Cassar ,Stephen Taylor ,Teresa Lambe ,Rebecca Young ,Rachel Halkerston ,Stephen J Thomas ,Luke Blackwell ,Patpong Rongkard ,Sven Kerneis ,Esme Weeks ,Lizzie Stafford ,Yolanda Lie ,Timothy Tipoe ,Helen Brown ,Shona C Moore ,Laura Silva-Reyes ,James T Grist ,Christopher Duncan ,Miles W Carroll ,Denise O’donnell ,Susanna Dunachie

doi:10.1038/s41467-022-28898-1

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.

Highlights

The trajectories of acquired immunity to severe acute respiratory syndrome coronavirus 2 infection are not fully understood
A particular concern is the identification of SARSCoV-2 variants of concern (VOC) (B.1.1.7-alpha, B.1.351-beta, P.1-gamma and B.1.617.2-delta), with mutations which are associated with an increase in transmissibility, severity or escape from vaccine or SARS-CoV-2-induced immunity[20–28]
We examined the magnitude of the T cell response to SARS-CoV-2 using an ex vivo IFN-γ Enzyme-Linked immunospot (ELISpot) assay at 28 days, 90-120 days and 180 days after SARS-CoV-2 infection N = 64–78 Healthcare workers (HCW)/timepoint, 57 participants at all timepoints, and 6 volunteers with severe COVID-19 at day 180 (Figs. 4a and 4b and Supplementary Table 3)

Summary

Introduction

The trajectories of acquired immunity to severe acute respiratory syndrome coronavirus 2 infection are not fully understood. 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 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. We evaluate the predictive value of clinical and immune parameters measured early after infection on the durability of immune responses using an integrative analysis with a machine learning platform (SIMON)[30,31] Using this approach, we define a group of high and low antibody responders with a differential capacity to neutralise the VOC

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Conclusion