Evidence map›Paper›PMID 40392230›Full record

ArticleThe Journal of infectious diseases2025

Hybrid B- and T-Cell Immunity Associates With Protection Against Breakthrough Infection After Severe Acute Respiratory Syndrome Coronavirus 2 Vaccination in Avon Longitudinal Study of Parents and Children (ALSPAC) Participants.

Holly E Baum, Marianna Santopaolo, Ore Francis, Emily J Milodowski, Katrina Entwistle, Elizabeth Oliver, Benjamin Hitchings, Divya Diamond, Amy C Thomas, Ruth E Mitchell and 21 more

Erratum issuedAbstract read
In one paragraph

Article in The Journal of infectious diseases, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Post-Vaccination COVID-19 Infection among Health Care Workers: Description, Determinants, and Event-History Analysis.Indian journal of community medicine : official publication of Indian Association of Preventive & Social Medicine
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

31 authors.

Holly E BaumSchool of Cellular and Molecular Medicine, Faculty of Health and Life Sciences, University of Bristol, Bristol, United Kingdom.ORCID 0000-0002-1311-6446
Marianna SantopaoloSchool of Cellular and Molecular Medicine, Faculty of Health and Life Sciences, University of Bristol, Bristol, United Kingdom.
Ore FrancisSchool of Cellular and Molecular Medicine, Faculty of Health and Life Sciences, University of Bristol, Bristol, United Kingdom.
Emily J MilodowskiBristol Veterinary School, Faculty of Health and Life Sciences, University of Bristol, Bristol, United Kingdom.
Katrina EntwistleBristol Veterinary School, Faculty of Health and Life Sciences, University of Bristol, Bristol, United Kingdom.ORCID 0009-0002-7166-8318
Elizabeth OliverSchool of Cellular and Molecular Medicine, Faculty of Health and Life Sciences, University of Bristol, Bristol, United Kingdom.
Benjamin HitchingsSchool of Cellular and Molecular Medicine, Faculty of Health and Life Sciences, University of Bristol, Bristol, United Kingdom.ORCID 0000-0001-5248-9061
Divya DiamondSchool of Cellular and Molecular Medicine, Faculty of Health and Life Sciences, University of Bristol, Bristol, United Kingdom.
Amy C ThomasPopulation Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom.
Ruth E MitchellPopulation Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom.
Milla KibblePopulation Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom.
Kapil GuptaSchool of Biochemistry, Faculty of Health and Life Sciences, University of Bristol, Bristol, United Kingdom.
Natalie Di BartoloSchool of Biochemistry, Faculty of Health and Life Sciences, University of Bristol, Bristol, United Kingdom.
Paul KlenermanDivision of Structural Biology, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.ORCID 0000-0003-4307-9161
Anthony BrownPeter Medawar Building for Pathogen Research, University of Oxford, Oxford, United Kingdom.
Begonia Morales-AzaSchool of Cellular and Molecular Medicine, Faculty of Health and Life Sciences, University of Bristol, Bristol, United Kingdom.
Jennifer OliverBristol Vaccine Centre, University of Bristol, Bristol, United Kingdom.
Imre BergerSchool of Biochemistry, Faculty of Health and Life Sciences, University of Bristol, Bristol, United Kingdom.ORCID 0000-0001-7518-9045
Ash M ToyeSchool of Biochemistry, Faculty of Health and Life Sciences, University of Bristol, Bristol, United Kingdom.
Adam FinnSchool of Cellular and Molecular Medicine, Faculty of Health and Life Sciences, University of Bristol, Bristol, United Kingdom.
Anu GoenkaSchool of Cellular and Molecular Medicine, Faculty of Health and Life Sciences, University of Bristol, Bristol, United Kingdom.ORCID 0000-0002-8152-2155
Andrew D DavidsonSchool of Cellular and Molecular Medicine, Faculty of Health and Life Sciences, University of Bristol, Bristol, United Kingdom.
Susan RingPopulation Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom.ORCID 0000-0003-3103-9330
Lynn MolloyPopulation Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom.
Melanie LewcockPopulation Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom.
Kate NorthstonePopulation Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom.ORCID 0000-0002-0602-1983
Firona RothPopulation Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom.
Nicholas J TimpsonPopulation Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom.ORCID 0000-0002-7141-9189
Linda WooldridgeBristol Veterinary School, Faculty of Health and Life Sciences, University of Bristol, Bristol, United Kingdom.ORCID 0000-0002-6213-347X
Alice HallidaySchool of Cellular and Molecular Medicine, Faculty of Health and Life Sciences, University of Bristol, Bristol, United Kingdom.ORCID 0000-0001-8183-1110
Laura RivinoSchool of Cellular and Molecular Medicine, Faculty of Health and Life Sciences, University of Bristol, Bristol, United Kingdom.ORCID 0000-0001-6213-9794

Funding

Academy of Medical Sciences SB007/100173ALSPACAvon Longitudinal Study of Parents and Children (ALSPAC)CRUK Integrative Cancer Epidemiology Programme C18281/A29019Elizabeth Blackwell InstituteIntegrative Epidemiology Unit MC_UU_00011/1Medical Research Council WT 217065/Z/19/ZMRC MR/W021315/1UK Research and Innovation MR/V028448/1University of BristolUniversity of Bristol National Institute for Health and Care Research Biomedical Research Centre BRC-1215-2001University's Alumni and FriendsWellcome TrustWellcome Trust 102215/2/13/2Wellcome Trust 204813/Z/16/ZWellcome Trust 217065/Z/19/Z
6 · The paper itself

Abstract

backgroundImmunological memory to vaccination and viral infection involves the coordinated action of B and T cells; thus, integrated analysis of these 2 components is critical for understanding their respective contributions to protection against breakthrough infections (BIs) after vaccination.

methodsWe investigated cellular and humoral immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and/or vaccination in 300 adult participants from the Avon Longitudinal Study of Parents and Children (ALSPAC). Participants were grouped by those with (cases) and without (controls) a history of SARS-CoV-2 infection. To provide a quantitative correlate for protection against BI in the 8-month period after the study, Youden index thresholds were calculated for all immune measures analyzed.

resultsThe magnitude of antibody and T-cell responses following the second vaccine dose was associated with protection against BI in participants with a history of SARS-CoV-2 infection (cases), but not in infection-naive controls. Over 8 months of follow-up, 2 threshold combinations provided the best performance for protection against BI in cases: (i) anti-spike immunoglobulin G (IgG) (≥666.4 binding antibody units [BAU]/mL) combined with anti-nucleocapsid pan-immunoglobulin (pan-Ig) (≥0.1332 BAU/mL) and (ii) spike 1-specific T cells (≥195.6 spot-forming units/106 peripheral blood mononuclear cells) combined with anti-N pan-Ig (≥0.1332 BAU/mL). Both combinations offered 100% specificity for detecting cases without BI, with sensitivities of 83.3% and 72.2%, respectively.

conclusionsCollectively, these results suggest that hybrid B- and T-cell immunity offers superior protection from BI after coronavirus disease 2019 (COVID-19) vaccination, and this finding has implications for designing next-generation COVID-19 vaccines that are capable of eliciting immunity to a broader repertoire of SARS-CoV-2 proteins.

Indexed as

B-LymphocytesCOVID-19COVID-19 VaccinesSARS-CoV-2T-LymphocytesAdolescentAdultAntibodies, ViralBreakthrough InfectionsChildFemaleHumansImmunity, CellularImmunologic MemoryLongitudinal StudiesMaleAntibodies, ViralCOVID-19 VaccinesALSPACbreakthrough infectionhybrid immunitySARS-CoV-2vaccination

Identifiers

PMID40392230
PMCPMC12349941

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Registered trials

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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.