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

10.1038/s41467-022-28898-1

Nature Communications

Contributing to research themes:

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.

Author list:

Affiliations

  1. Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK. 
  2. Peter Medawar Building for Pathogen Research, Nuffield Dept. of Clinical Medicine, University of Oxford, Oxford, UK. 
  3. Oxford University Hospitals NHS Foundation Trust, Oxford, UK. 
  4. Nuffield Dept of Clinical Neuroscience, University of Oxford, Oxford, UK. 
  5. NIHR Oxford Biomedical Research Centre, Oxford, UK. 
  6. United Kingdom Health Security Agency, Porton Down, Wiltshire, England. 
  7. Department of Clinical Biochemistry, Oxford University Hospitals NHS Foundation Trust, Oxford, UK. 
  8. Jenner Institute, University of Oxford, Oxford, UK. 
  9. The Florey Institute for Host-Pathogen Interactions and Department of Infection, Immunity and Cardiovascular Disease, Medical School, University of Sheffield, Sheffield, UK. 
  10. Big Data Institute, Nuffield Dept. of Population Health, University of Oxford, Oxford, UK. 
  11. Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford, UK. 
  12. James & Lillian Martin Centre, Sir William Dunn School of Pathology, University of Oxford, Oxford, UK. 
  13. Oxford University Medical School, Medical Sciences Division, University of Oxford, Oxford, UK. 
  14. Oxford Centre For Global Health Research, Nuffield Dept. of Clinical Medicine, University of Oxford, Oxford, UK. 
  15. Monogram Biosciences LabCorp, San Francisco, CA, USA. 
  16. Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK. 
  17. Mahidol-Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, Thailand. 
  18. HPRU in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK. 
  19. Tropical and Infectious Disease Unit, Liverpool University Hospitals NHS Foundation Trust (a member of Liverpool Health Partners), Liverpool, UK. 
  20. Peter Medawar Building for Pathogen Research, Department of Paediatrics, University of Oxford, Oxford, UK. 
  21. Nuffield Department of Medicine, University of Oxford, Oxford, UK. 
  22. Radcliffe Department of Medicine, University of Oxford, Oxford, UK. 
  23. Translational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford, Oxford, UK. 

Authors

Adriana Tomic1, Donal T. Skelly2,3,4, Ane Ogbe2, Daniel O’Connor1,5, Matthew Pace2, Emily Adland2, Frances Alexander6, Mohammad Ali2, Kirk Allott7, M. Azim Ansari2, Sandra Belij-Rammerstorfer8, Sagida Bibi1, Luke Blackwell1, Anthony Brown2, Helen Brown2, Breeze Cavell6, Elizabeth A. Clutterbuck1, Thushan de Silva9, David Eyre3,10, Sheila Lumley2,3, Amy Flaxman8, James Grist11, Carl-Philipp Hackstein2, Rachel Halkerston6, Adam C. Harding12, Jennifer Hill1,5, Tim James7, Cecilia Jay2, Síle A. Johnson2,3,13, Barbara Kronsteiner2,14, Yolanda Lie15, Aline Linder1,5, Stephanie Longet6,16, Spyridoula Marinou1,5, Philippa C. Matthews2,3,5, Jack Mellors6, Christos Petropoulos15, Patpong Rongkard2,17, Cynthia Sedik15, Laura Silva-Reyes1,5, Holly Smith8, Lisa Stockdale1,5, Stephen Taylor6, Stephen Thomas6, Timothy Tipoe2, Lance Turtle18,19, Vinicius Adriano Vieira Terri Wrin15, OPTIC Clinical Group*, PITCH Study Group*, C-MORE Group*, Andrew J. Pollard1,5, Teresa Lambe8, Chris P. Conlon21, Katie Jeffery3,22, Simon Travis3,23, Philip Goulder20, John Frater2,3, Alex J. Mentzer3,16, Lizzie Stafford21, Miles W. Carroll6,16, William S. James12, Paul Klenerman2,3,5,23, Eleanor Barnes2,3,5,23, Christina Dold1,5 & Susanna J. Dunachie2,3,14,17