Divergent trajectories of antiviral memory after SARS-CoV-2 infection
Adriana Tomić, Donal 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 E. Cavell, Elizabeth Clutterbuck, Thushan I. de Silva, David W. Eyre, Sheila Lumley, Amy Flaxman, James T. Grist, Carl-Philipp Hackstein, Rachel Halkerston, Adam 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 J. Petropoulos, Patpong Rongkard, Cynthia Sedik, Laura Silva-Reyes, Holly Smith, Lisa Stockdale, Stephen Taylor, Stephen J. Thomas, Timothy Tipoe, Lance Turtle, Vinícius Vieira, Terri Wrin, Lizzie Stafford, Hibatullah Abuelgasim, Ahmed Alhussni, Carolina V. Arancibia-Cárcamo, Martyna Borak, Joseph Cutteridge, Alexandra Deeks, Lucy Denly, Stavros Dimitriadis, Shayan Fassih, Thomas Foord, Thomas Fordwoh, Jennifer Holmes, Bryn Horsington, Sven Kerneis, David Kim, Katy Lillie, Jordan Morrow, Denise O’Donnell, Thomas Ritter, Beatrice Simmons, A Taylor, Sarah Thomas, Yolanda Warren, Adam Watson, Esme Weeks, Robert Wilson, Rebecca Young, PITCH Study Group, C.J. Duncan, Shona C. Moore, Rebecca Payne, Alex Richter, Sarah Rowland‐Jones, C-MORE Group, Alexander J. Mentzer, Mark Philip Cassar, Tao Dong, Anastasia Fries, Javier Gilbert‐Jaramillo, Ling‐Pei Ho, Julian C. Knight, Stefan Neubauer, Yanchun Peng, Nayia Petousi, Betty Raman, Nick P. Talbot, Andrew J. Pollard, Teresa Lambe, Chris Conlon, Katie Jeffery, Simon Travis
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.