Evidence map›Paper›PMID 40848990›Full record

Observational studyThe Journal of infection2025

Third exposure to COVID-19 infection or vaccination differentially impacts T cell responses.

Gift Ahimbisibwe, David Greenwood, Katalin Andrea Wilkinson, Joshua Gahir, Hermaleigh Townsley, Murad Miah, Philip Bawumia, Charlotte Chaloner, Dina Levi, Philip Hobson and 28 more

Registry-linked trialAbstract readMulticenter StudyObservational Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in The Journal of infection, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04750356 (SARS-CoV-2 Longitudinal Study), which is not on this map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT04750356 unknown statusnot on this map

SARS-CoV-2 Longitudinal Study: Understanding Susceptibility, Transmission and Disease Severity

TypeobservationalSponsorUniversity College, LondonRan2021 to 2024Enrolled6,000ConditionsSARS-CoV Infection
3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

38 authors.

Gift AhimbisibweThe Francis Crick Institute, NW1 1AT London, UK.
David GreenwoodThe Francis Crick Institute, NW1 1AT London, UK.
Katalin Andrea WilkinsonThe Francis Crick Institute, NW1 1AT London, UK; Welcome Discovery Research Platforms in Infection, Centre for Infectious Diseases Research in Africa (CIDRI-Africa), Institute of Infectious Disease and Molecular Medicine and Department of Medicine, University of Cape Town, Cape Town 7925, Republic of South Africa.
Joshua GahirThe Francis Crick Institute, NW1 1AT London, UK; National Institute for Health Research (NIHR) University College London Hospitals (UCLH) Biomedical Research Centre and NIHR UCLH Clinical Research Facility, UK.
Hermaleigh TownsleyThe Francis Crick Institute, NW1 1AT London, UK; National Institute for Health Research (NIHR) University College London Hospitals (UCLH) Biomedical Research Centre and NIHR UCLH Clinical Research Facility, UK.
Murad MiahThe Francis Crick Institute, NW1 1AT London, UK.
Philip BawumiaThe Francis Crick Institute, NW1 1AT London, UK.
Charlotte ChalonerThe Francis Crick Institute, NW1 1AT London, UK; University College London, Gower Street, London, Uk.
Dina LeviThe Francis Crick Institute, NW1 1AT London, UK.
Philip HobsonThe Francis Crick Institute, NW1 1AT London, UK.
Andy RiddellThe Francis Crick Institute, NW1 1AT London, UK.
Agnieszka HobbsCOVID Surveillance Unit, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Giulia DowgierCOVID Surveillance Unit, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Rebecca PennThe Francis Crick Institute, NW1 1AT London, UK.
Theo SandersonThe Francis Crick Institute, NW1 1AT London, UK.
Phoebe Stevenson-LeggettCOVID Surveillance Unit, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Odiesia DaleyThe Francis Crick Institute, NW1 1AT London, UK.
James BazireCOVID Surveillance Unit, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Ruth HarveyWorldwide Influenza Centre, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Ashley S FowlerThe Francis Crick Institute, NW1 1AT London, UK.
Callie SmithKing's College London, St Thomas' Campus, Westminster Bridge Road, London, UK.
Mauro MirandaThe Francis Crick Institute, NW1 1AT London, UK.
Nicola O'ReillyThe Francis Crick Institute, NW1 1AT London, UK.
Scott WarchalThe Francis Crick Institute, NW1 1AT London, UK.
Karen AmbroseThe Francis Crick Institute, NW1 1AT London, UK.
Amy StrangeThe Francis Crick Institute, NW1 1AT London, UK.
Gavin KellyThe Francis Crick Institute, NW1 1AT London, UK.
Svend KjarThe Francis Crick Institute, NW1 1AT London, UK.
Legacy Investigators
Bryan WilliamsNational Institute for Health Research (NIHR) University College London Hospitals (UCLH) Biomedical Research Centre and NIHR UCLH Clinical Research Facility, UK; University College London, Gower Street, London, Uk.
Vincenzo LibriNational Institute for Health Research (NIHR) University College London Hospitals (UCLH) Biomedical Research Centre and NIHR UCLH Clinical Research Facility, UK; University College London, Gower Street, London, Uk.
Steve GamblinThe Francis Crick Institute, NW1 1AT London, UK.
Sonia GandhiThe Francis Crick Institute, NW1 1AT London, UK; University College London, Gower Street, London, Uk.
Charles SwantonThe Francis Crick Institute, NW1 1AT London, UK; University College London, Gower Street, London, Uk.
David Lv BauerThe Francis Crick Institute, NW1 1AT London, UK; Genotype-to-Phenotype 2 Consortium (G2P2-UK), UK.
Robert John WilkinsonThe Francis Crick Institute, NW1 1AT London, UK; Welcome Discovery Research Platforms in Infection, Centre for Infectious Diseases Research in Africa (CIDRI-Africa), Institute of Infectious Disease and Molecular Medicine and Department of Medicine, University of Cape Town, Cape Town 7925, Republic of South Africa; Department of Infectious Diseases, Imperial College London, W12 0NN London, UK.
Edward J CarrThe Francis Crick Institute, NW1 1AT London, UK; University College London, Gower Street, London, Uk.
Emma C WallThe Francis Crick Institute, NW1 1AT London, UK; National Institute for Health Research (NIHR) University College London Hospitals (UCLH) Biomedical Research Centre and NIHR UCLH Clinical Research Facility, UK; Research Department of Infection, Division of Infection and Immunity, University College London, UK. Electronic address: emma.wall@crick.ac.uk.

Funding

Wellcome Trust 222574Wellcome Trust 226817Wellcome Trust CC0102Wellcome Trust CC1114Wellcome Trust CC1283Wellcome Trust CC2041Wellcome Trust CC2060Wellcome Trust CC2112Wellcome Trust CC2166
6 · The paper itself

Abstract

backgroundIn 2021, the rapid rollout of two doses of SARS-CoV-2 vaccines reduced COVID-19 severity and mortality. However, further vaccine doses as a prime-boost schedule were limited, and lifting of public health restrictions by late 2021 frequently led to infection, rather than vaccine, as a third exposure.

objectiveTo compare how the third exposure through mRNA booster or SARS-CoV-2 infection shapes humoral and cellular immunity following two vaccine doses.

methodsWe compared immune responses after the third exposure in healthy adults enrolled in the UCLH-Crick Legacy cohort study (NCT04750356) between those receiving ancestral spike-encoded mRNA booster (vaccine immunity, n = 38) or COVID-19 infection (hybrid immunity, n = 13) following two vaccine doses. Immune profiles were evaluated using live virus neutralization assays, IFN-γ ELISpot, Luminex assay, flow cytometry and mass cytometry.

resultsBoth total anti-Spike IgG and variant-specific neutralising antibodies were comparable following infection or vaccine as a third exposure. Overall, T cell populations were similar but functionally different. CD8⁺ Effector Memory (TEM) cells in the vaccine group showed higher expression of CD69 and Granzyme B following stimulation with SARS-CoV-2 Spike peptides. In contrast, the hybrid group produced higher levels of innate immune associated cytokines IL-10 and IL-34, as well as the T cell homing chemokine CCL25, after stimulation.

conclusionsWhile both exposures generated comparable breadth of protection against SARS-CoV-2 variants, our findings suggest that the route of third exposure influences different aspects of the immune response, warranting further investigation into long-term immunity at both systemic and mucosal sites.

Indexed as

COVID-19COVID-19 VaccinesImmunization, SecondarySARS-CoV-2T-LymphocytesAdultAntibodies, NeutralizingAntibodies, ViralCohort StudiesFemaleHumansImmunity, CellularImmunity, HumoralMaleMiddle AgedSpike Glycoprotein, CoronavirusAntibodies, NeutralizingAntibodies, ViralCOVID-19 VaccinesSpike Glycoprotein, CoronavirusImmunityInfection exposureSARS-CoV-2T cellsVaccination

Identifiers

PMID40848990
PMCPMC7618389

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.