{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T17:28:26Z","timestamp":1780766906833,"version":"3.54.1"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T00:00:00Z","timestamp":1747699200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014013","name":"UK Research and Innovation","doi-asserted-by":"publisher","award":["MR\/V028448\/1"],"award-info":[{"award-number":["MR\/V028448\/1"]}],"id":[{"id":"10.13039\/100014013","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100019415","name":"Elizabeth Blackwell Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100019415","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000883","name":"University of Bristol","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000883","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["204813\/Z\/16\/Z"],"award-info":[{"award-number":["204813\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["217065\/Z\/19\/Z"],"award-info":[{"award-number":["217065\/Z\/19\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["102215\/Z\/13\/Z"],"award-info":[{"award-number":["102215\/Z\/13\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University's Alumni and Friends"},{"name":"Avon Longitudinal Study of Parents and Children"},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["WT 217065\/Z\/19\/Z"],"award-info":[{"award-number":["WT 217065\/Z\/19\/Z"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University of Bristol National Institute for Health and Care Research Biomedical Research Centre","award":["BRC-1215-2001"],"award-info":[{"award-number":["BRC-1215-2001"]}]},{"name":"Integrative Epidemiology Unit","award":["MC_UU_00011\/1"],"award-info":[{"award-number":["MC_UU_00011\/1"]}]},{"name":"CRUK Integrative Cancer Epidemiology Programme","award":["C18281\/A29019"],"award-info":[{"award-number":["C18281\/A29019"]}]},{"DOI":"10.13039\/100018645","name":"MRC","doi-asserted-by":"publisher","award":["MR\/W021315\/1"],"award-info":[{"award-number":["MR\/W021315\/1"]}],"id":[{"id":"10.13039\/100018645","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000691","name":"Academy of Medical Sciences","doi-asserted-by":"publisher","award":["SB007\/100173"],"award-info":[{"award-number":["SB007\/100173"]}],"id":[{"id":"10.13039\/501100000691","id-type":"DOI","asserted-by":"publisher"}]},{"name":"ALSPAC"},{"name":"ALSPAC"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,8,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Immunological 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The 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) (\u2265666.4 binding antibody units [BAU]\/mL) combined with anti-nucleocapsid pan-immunoglobulin (pan-Ig) (\u22650.1332 BAU\/mL) and (ii) spike 1\u2013specific T cells (\u2265195.6 spot-forming units\/106 peripheral blood mononuclear cells) combined with anti-N pan-Ig (\u22650.1332 BAU\/mL). Both combinations offered 100% specificity for detecting cases without BI, with sensitivities of 83.3% and 72.2%, respectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Collectively, 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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/infdis\/jiaf246","type":"journal-article","created":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T08:14:21Z","timestamp":1747296861000},"page":"e327-e340","source":"Crossref","is-referenced-by-count":4,"title":["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"],"prefix":"10.1093","volume":"232","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1311-6446","authenticated-orcid":false,"given":"Holly E","family":"Baum","sequence":"first","affiliation":[{"name":"School of Cellular and Molecular Medicine, Faculty of Health and Life Sciences, University of Bristol , Bristol ,","place":["United Kingdom"]},{"name":"Bristol Vaccine Centre, University of Bristol , Bristol ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianna","family":"Santopaolo","sequence":"additional","affiliation":[{"name":"School of Cellular and Molecular Medicine, Faculty of Health and Life Sciences, University of Bristol , Bristol ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ore","family":"Francis","sequence":"additional","affiliation":[{"name":"School of Cellular and Molecular Medicine, Faculty of Health and Life Sciences, University of Bristol , Bristol ,","place":["United Kingdom"]},{"name":"Bristol Veterinary School, Faculty of Health and Life Sciences, University of Bristol , Bristol ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily J","family":"Milodowski","sequence":"additional","affiliation":[{"name":"Bristol Veterinary School, Faculty of Health and Life Sciences, University of Bristol , Bristol ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7166-8318","authenticated-orcid":false,"given":"Katrina","family":"Entwistle","sequence":"additional","affiliation":[{"name":"Bristol Veterinary School, Faculty of Health and Life Sciences, University of Bristol , Bristol ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Oliver","sequence":"additional","affiliation":[{"name":"School of Cellular and Molecular Medicine, Faculty of Health and Life Sciences, University of Bristol , Bristol ,","place":["United Kingdom"]},{"name":"Bristol Vaccine Centre, University of Bristol , Bristol ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5248-9061","authenticated-orcid":false,"given":"Benjamin","family":"Hitchings","sequence":"additional","affiliation":[{"name":"School of Cellular and Molecular Medicine, Faculty of Health and Life Sciences, University of Bristol , Bristol ,","place":["United Kingdom"]},{"name":"Bristol Vaccine Centre, University of Bristol , Bristol ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Divya","family":"Diamond","sequence":"additional","affiliation":[{"name":"School of Cellular and Molecular Medicine, Faculty of Health and Life Sciences, University of Bristol , Bristol ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy C","family":"Thomas","sequence":"additional","affiliation":[{"name":"Population Health Sciences, Bristol Medical School, University of Bristol , Bristol ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth E","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Population Health Sciences, Bristol Medical School, University of Bristol , Bristol ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milla","family":"Kibble","sequence":"additional","affiliation":[{"name":"Population Health Sciences, Bristol Medical School, University of Bristol , Bristol ,","place":["United Kingdom"]},{"name":"Department of Applied Mathematics and Theoretical Physics, University of Cambridge , Cambridge ,","place":["United Kingdom"]},{"name":"Department of Twin Research and Genetic Epidemiology, King's College London , London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kapil","family":"Gupta","sequence":"additional","affiliation":[{"name":"School of Biochemistry, Faculty of Health and Life Sciences, University of Bristol , Bristol ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"Di Bartolo","sequence":"additional","affiliation":[{"name":"School of Biochemistry, Faculty of Health and Life Sciences, University of Bristol , Bristol ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4307-9161","authenticated-orcid":false,"given":"Paul","family":"Klenerman","sequence":"additional","affiliation":[{"name":"Division of Structural Biology, Nuffield Department of Medicine, University of Oxford , Oxford ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Brown","sequence":"additional","affiliation":[{"name":"Peter Medawar Building for Pathogen Research, University of Oxford , Oxford ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Begonia","family":"Morales-Aza","sequence":"additional","affiliation":[{"name":"School of Cellular and Molecular Medicine, Faculty of Health and Life Sciences, University of Bristol , Bristol ,","place":["United Kingdom"]},{"name":"Bristol Vaccine Centre, University of Bristol , Bristol ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Oliver","sequence":"additional","affiliation":[{"name":"Bristol Vaccine Centre, University of Bristol , Bristol ,","place":["United Kingdom"]},{"name":"Population Health Sciences, Bristol Medical School, University of Bristol , Bristol ,","place":["United 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J","family":"Timpson","sequence":"additional","affiliation":[{"name":"Population Health Sciences, Bristol Medical School, University of Bristol , Bristol ,","place":["United Kingdom"]},{"name":"Medical Research Council Integrative Epidemiology Unit, University of Bristol , Bristol ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6213-347X","authenticated-orcid":false,"given":"Linda","family":"Wooldridge","sequence":"additional","affiliation":[{"name":"Bristol Veterinary School, Faculty of Health and Life Sciences, University of Bristol , Bristol ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8183-1110","authenticated-orcid":false,"given":"Alice","family":"Halliday","sequence":"additional","affiliation":[{"name":"School of Cellular and Molecular Medicine, Faculty of Health and Life Sciences, University of Bristol , Bristol ,","place":["United Kingdom"]},{"name":"Bristol Vaccine Centre, University of Bristol , Bristol ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6213-9794","authenticated-orcid":false,"given":"Laura","family":"Rivino","sequence":"additional","affiliation":[{"name":"School of Cellular and Molecular Medicine, Faculty of Health and Life Sciences, University of Bristol , Bristol ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,5,20]]},"reference":[{"key":"2026031811361908200_jiaf246-B1","doi-asserted-by":"crossref","first-page":"3528","DOI":"10.1038\/s41467-022-30836-0","article-title":"Long COVID burden and risk factors in 10 UK longitudinal studies and electronic health records","volume":"13","author":"Thompson","year":"2022","journal-title":"Nat 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