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Cross-reactive memory T cells associate with protection against SARS-CoV-2 infection in COVID-19 contacts

Author

Listed:
  • Rhia Kundu

    (Imperial College London
    Imperial College London)

  • Janakan Sam Narean

    (Imperial College London
    Imperial College London)

  • Lulu Wang

    (Imperial College London
    Imperial College London)

  • Joseph Fenn

    (Imperial College London
    Imperial College London)

  • Timesh Pillay

    (Imperial College London
    Imperial College London)

  • Nieves Derqui Fernandez

    (Imperial College London
    Imperial College London)

  • Emily Conibear

    (Imperial College London
    Imperial College London)

  • Aleksandra Koycheva

    (Imperial College London
    Imperial College London)

  • Megan Davies

    (Imperial College London
    Imperial College London)

  • Mica Tolosa-Wright

    (Imperial College London
    Imperial College London)

  • Seran Hakki

    (Imperial College London
    Imperial College London)

  • Robert Varro

    (Imperial College London
    Imperial College London)

  • Eimear McDermott

    (Imperial College London
    Imperial College London)

  • Sarah Hammett

    (Imperial College London
    Imperial College London)

  • Jessica Cutajar

    (Imperial College London
    Imperial College London)

  • Ryan S. Thwaites

    (Imperial College London)

  • Eleanor Parker

    (Imperial College London)

  • Carolina Rosadas

    (Imperial College London)

  • Myra McClure

    (Imperial College London)

  • Richard Tedder

    (Imperial College London)

  • Graham P. Taylor

    (Imperial College London)

  • Jake Dunning

    (National Infection Service, Public Health England
    NIHR HPRU in Emerging and Zoonotic Infections)

  • Ajit Lalvani

    (Imperial College London
    Imperial College London)

Abstract

Cross-reactive immune responses to SARS-CoV-2 have been observed in pre-pandemic cohorts and proposed to contribute to host protection. Here we assess 52 COVID-19 household contacts to capture immune responses at the earliest timepoints after SARS-CoV-2 exposure. Using a dual cytokine FLISpot assay on peripheral blood mononuclear cells, we enumerate the frequency of T cells specific for spike, nucleocapsid, membrane, envelope and ORF1 SARS-CoV-2 epitopes that cross-react with human endemic coronaviruses. We observe higher frequencies of cross-reactive (p = 0.0139), and nucleocapsid-specific (p = 0.0355) IL-2-secreting memory T cells in contacts who remained PCR-negative despite exposure (n = 26), when compared with those who convert to PCR-positive (n = 26); no significant difference in the frequency of responses to spike is observed, hinting at a limited protective function of spike-cross-reactive T cells. Our results are thus consistent with pre-existing non-spike cross-reactive memory T cells protecting SARS-CoV-2-naïve contacts from infection, thereby supporting the inclusion of non-spike antigens in second-generation vaccines.

Suggested Citation

  • Rhia Kundu & Janakan Sam Narean & Lulu Wang & Joseph Fenn & Timesh Pillay & Nieves Derqui Fernandez & Emily Conibear & Aleksandra Koycheva & Megan Davies & Mica Tolosa-Wright & Seran Hakki & Robert Va, 2022. "Cross-reactive memory T cells associate with protection against SARS-CoV-2 infection in COVID-19 contacts," Nature Communications, Nature, vol. 13(1), pages 1-8, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-021-27674-x
    DOI: 10.1038/s41467-021-27674-x
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    1. Jaime S. Rosa Duque & Xiwei Wang & Daniel Leung & Samuel M. S. Cheng & Carolyn A. Cohen & Xiaofeng Mu & Asmaa Hachim & Yanmei Zhang & Sau Man Chan & Sara Chaothai & Kelvin K. H. Kwan & Karl C. K. Chan, 2022. "Immunogenicity and reactogenicity of SARS-CoV-2 vaccines BNT162b2 and CoronaVac in healthy adolescents," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    2. Daan K. J. Pieren & Sebastián G. Kuguel & Joel Rosado & Alba G. Robles & Joan Rey-Cano & Cristina Mancebo & Juliana Esperalba & Vicenç Falcó & María J. Buzón & Meritxell Genescà, 2023. "Limited induction of polyfunctional lung-resident memory T cells against SARS-CoV-2 by mRNA vaccination compared to infection," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    3. Tabea M. Eser & Olga Baranov & Manuel Huth & Mohammed I. M. Ahmed & Flora Deák & Kathrin Held & Luming Lin & Kami Pekayvaz & Alexander Leunig & Leo Nicolai & Georgios Pollakis & Marcus Buggert & David, 2023. "Nucleocapsid-specific T cell responses associate with control of SARS-CoV-2 in the upper airways before seroconversion," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    4. Martin J. Scurr & George Lippiatt & Lorenzo Capitani & Kirsten Bentley & Sarah N. Lauder & Kathryn Smart & Michelle S. Somerville & Tara Rees & Richard J. Stanton & Awen Gallimore & James P. Hindley &, 2022. "Magnitude of venous or capillary blood-derived SARS-CoV-2-specific T cell response determines COVID-19 immunity," Nature Communications, Nature, vol. 13(1), pages 1-9, December.
    5. Joseph A. Lewnard & Vennis Hong & Jeniffer S. Kim & Sally F. Shaw & Bruno Lewin & Harpreet Takhar & Sara Y. Tartof, 2023. "Association of SARS-CoV-2 BA.4/BA.5 Omicron lineages with immune escape and clinical outcome," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    6. Christine D. Palmer & Ciaran D. Scallan & Lauren D. Kraemer Tardif & Melissa A. Kachura & Amy R. Rappaport & Daniel O. Koralek & Alison Uriel & Leonid Gitlin & Joshua Klein & Matthew J. Davis & Harshn, 2023. "GRT-R910: a self-amplifying mRNA SARS-CoV-2 vaccine boosts immunity for ≥6 months in previously-vaccinated older adults," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    7. Hassen Kared & Asia-Sophia Wolf & Amin Alirezaylavasani & Anthony Ravussin & Guri Solum & Trung The Tran & Fridtjof Lund-Johansen & John Torgils Vaage & Lise Sofie Nissen-Meyer & Unni C. Nygaard & Ola, 2022. "Immune responses in Omicron SARS-CoV-2 breakthrough infection in vaccinated adults," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    8. Rúbens Prince dos Santos Alves & Julia Timis & Robyn Miller & Kristen Valentine & Paolla Beatriz Almeida Pinto & Andrew Gonzalez & Jose Angel Regla-Nava & Erin Maule & Michael N. Nguyen & Norazizah Sh, 2024. "Human coronavirus OC43-elicited CD4+ T cells protect against SARS-CoV-2 in HLA transgenic mice," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    9. Magen E. Francis & Ethan B. Jansen & Anthony Yourkowski & Alaa Selim & Cynthia L. Swan & Brian K. MacPhee & Brittany Thivierge & Rachelle Buchanan & Kerry J. Lavender & Joseph Darbellay & Matthew B. R, 2023. "Previous infection with seasonal coronaviruses does not protect male Syrian hamsters from challenge with SARS-CoV-2," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    10. Atienza-Diez, Iker & Seoane, Luís F., 2023. "Long- and short-term effects of cross-immunity in epidemic dynamics," Chaos, Solitons & Fractals, Elsevier, vol. 174(C).
    11. Jernej Pušnik & Werner O. Monzon-Posadas & Jasmin Zorn & Kathrin Peters & Maximilian Baum & Hannah Proksch & Celina Beta Schlüter & Galit Alter & Tanja Menting & Hendrik Streeck, 2023. "SARS-CoV-2 humoral and cellular immunity following different combinations of vaccination and breakthrough infection," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    12. Kai, Zhang & Sharaf, Mohamed & Wei, Siao-Yun & Shraah, Ata Al & Le, Luan Thanh & Arvind Bedekar, Dr Abhay & Bani Ahmad, Ahmad Y.A., 2024. "Exploring the asymmetric relationship between natural resources, fintech, remittance and environmental pollution for BRICS nations: New insights from MMQR approach," Resources Policy, Elsevier, vol. 90(C).
    13. Jernej Pušnik & Jasmin Zorn & Werner O. Monzon-Posadas & Kathrin Peters & Emmanuil Osypchuk & Sabine Blaschke & Hendrik Streeck, 2024. "Vaccination impairs de novo immune response to omicron breakthrough infection, a precondition for the original antigenic sin," Nature Communications, Nature, vol. 15(1), pages 1-13, December.

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