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

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. Clutterbuck, Thushan 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, Teresa Lambe, Chris P. Conlon, Katie Jeffery, Simon Travis, Philip Goulder, John Frater, Alex J. Mentzer, Lizzie Stafford, Miles W. Carroll, William S. James, Paul Klenerman, Eleanor Barnes (), Christina Dold and Susanna J. Dunachie
Additional contact information
Adriana Tomic: University of Oxford
Donal T. Skelly: University of Oxford
Ane Ogbe: University of Oxford
Daniel O’Connor: University of Oxford
Matthew Pace: University of Oxford
Emily Adland: University of Oxford
Frances Alexander: United Kingdom Health Security Agency, Porton Down
Mohammad Ali: University of Oxford
Kirk Allott: Oxford University Hospitals NHS Foundation Trust
M. Azim Ansari: University of Oxford
Sandra Belij-Rammerstorfer: University of Oxford
Sagida Bibi: University of Oxford
Luke Blackwell: University of Oxford
Anthony Brown: University of Oxford
Helen Brown: University of Oxford
Breeze Cavell: United Kingdom Health Security Agency, Porton Down
Elizabeth A. Clutterbuck: University of Oxford
Thushan Silva: University of Sheffield
David Eyre: Oxford University Hospitals NHS Foundation Trust
Sheila Lumley: University of Oxford
Amy Flaxman: University of Oxford
James Grist: University of Oxford
Carl-Philipp Hackstein: University of Oxford
Rachel Halkerston: United Kingdom Health Security Agency, Porton Down
Adam C. Harding: University of Oxford
Jennifer Hill: University of Oxford
Tim James: Oxford University Hospitals NHS Foundation Trust
Cecilia Jay: University of Oxford
Síle A. Johnson: University of Oxford
Barbara Kronsteiner: University of Oxford
Yolanda Lie: Monogram Biosciences LabCorp
Aline Linder: University of Oxford
Stephanie Longet: United Kingdom Health Security Agency, Porton Down
Spyridoula Marinou: University of Oxford
Philippa C. Matthews: University of Oxford
Jack Mellors: United Kingdom Health Security Agency, Porton Down
Christos Petropoulos: Monogram Biosciences LabCorp
Patpong Rongkard: University of Oxford
Cynthia Sedik: Monogram Biosciences LabCorp
Laura Silva-Reyes: University of Oxford
Holly Smith: University of Oxford
Lisa Stockdale: University of Oxford
Stephen Taylor: United Kingdom Health Security Agency, Porton Down
Stephen Thomas: United Kingdom Health Security Agency, Porton Down
Timothy Tipoe: University of Oxford
Lance Turtle: University of Liverpool
Vinicius Adriano Vieira: University of Oxford
Terri Wrin: Monogram Biosciences LabCorp
Andrew J. Pollard: University of Oxford
Teresa Lambe: University of Oxford
Chris P. Conlon: University of Oxford
Katie Jeffery: Oxford University Hospitals NHS Foundation Trust
Simon Travis: Oxford University Hospitals NHS Foundation Trust
Philip Goulder: University of Oxford
John Frater: University of Oxford
Alex J. Mentzer: Oxford University Hospitals NHS Foundation Trust
Lizzie Stafford: University of Oxford
Miles W. Carroll: United Kingdom Health Security Agency, Porton Down
William S. James: University of Oxford
Paul Klenerman: University of Oxford
Eleanor Barnes: University of Oxford
Christina Dold: University of Oxford
Susanna J. Dunachie: University of Oxford

Nature Communications, 2022, vol. 13, issue 1, 1-20

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-28898-1

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