{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T08:19:25Z","timestamp":1785831565355,"version":"3.56.0"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2024,5,14]],"date-time":"2024-05-14T00:00:00Z","timestamp":1715644800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI129709-03S1"],"award-info":[{"award-number":["AI129709-03S1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000030","name":"Centers for Disease Control and Prevention","doi-asserted-by":"publisher","award":["200-2016-91773"],"award-info":[{"award-number":["200-2016-91773"]}],"id":[{"id":"10.13039\/100000030","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000030","name":"Centers for Disease Control and Prevention","doi-asserted-by":"publisher","award":["U01 CA260539-03"],"award-info":[{"award-number":["U01 CA260539-03"]}],"id":[{"id":"10.13039\/100000030","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000030","name":"Centers for Disease Control and Prevention","doi-asserted-by":"publisher","award":["VA BX005507-01"],"award-info":[{"award-number":["VA BX005507-01"]}],"id":[{"id":"10.13039\/100000030","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,9,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Vaccines and vaccine boosting have blunted excess morbidity and mortality from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in older nursing home residents (NHR). However, the impact of repeated vaccination on the T-cell response based on biological sex and prior infection of NHR remain understudied.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We examined T-cell responses to SARS-CoV-2 mRNA vaccines in a cohort of NHR and healthcare workers (HCW) over 2 years. We used interferon-\u03b3 ELIspot and flow cytometry to assess T-cell response before, 2 weeks, and 6 months after the initial series and each of 2 booster vaccines. We analyzed these data longitudinally with mixed-effect modeling and also examined subsets of our cohorts for additional changes in T-cell effector function.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Prior SARS-CoV-2 infection and female sex contributed to higher T-cell response in NHR but not HCW. When looking across time points, NHR but not HCW with prior infection had significantly higher T-cell responses than infection-naive subjects. These patterns of response were maintained across multiple booster vaccinations.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>These results suggest that the age, multimorbidity, and\/or frailty of the NHR cohort may accentuate sex and infection status differences in T-cell response to mRNA vaccination.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/infdis\/jiae234","type":"journal-article","created":{"date-parts":[[2024,5,14]],"date-time":"2024-05-14T18:06:52Z","timestamp":1715710012000},"page":"635-644","source":"Crossref","is-referenced-by-count":4,"title":["Longitudinal Analysis of Nursing Home Residents\u2019 T-Cell Responses After SARS-CoV-2 mRNA Vaccinations Shows Influence of Biological Sex and Infection History"],"prefix":"10.1093","volume":"230","author":[{"given":"Carson L","family":"Smith","sequence":"first","affiliation":[{"name":"Department of Pathology, Case Western Reserve University School of Medicine , Cleveland, Ohio , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elise","family":"Didion","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease, Case Western Reserve University School of Medicine , Cleveland, Ohio , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Htin","family":"Aung","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease, Case Western Reserve University School of Medicine , Cleveland, Ohio , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Banumathi","family":"Tamilselvan","sequence":"additional","affiliation":[{"name":"Department of Nutrition, Case Western Reserve University , Cleveland, Ohio , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taissa","family":"Bej","sequence":"additional","affiliation":[{"name":"Geriatric Research, Education, and Clinical Center, Louis Stokes Veterans Affairs Northeast Ohio Healthcare System , Cleveland, Ohio , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oladayo A","family":"Oyebanji","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease, Case Western Reserve University School of Medicine , Cleveland, Ohio , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carey L","family":"Shive","sequence":"additional","affiliation":[{"name":"Department of Pathology, Case Western Reserve University School of Medicine , Cleveland, Ohio , USA"},{"name":"Geriatric Research, Education, and Clinical Center, Louis Stokes Veterans Affairs Northeast Ohio Healthcare System , Cleveland, Ohio , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brigid M","family":"Wilson","sequence":"additional","affiliation":[{"name":"Geriatric Research, Education, and Clinical Center, Louis Stokes Veterans Affairs Northeast Ohio Healthcare System , Cleveland, Ohio , USA"},{"name":"Division of Infectious Diseases and HIV Medicine, Case Western Reserve School of Medicine , Cleveland, Ohio , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Cameron","sequence":"additional","affiliation":[{"name":"Department of Population and Quantitative Health Sciences, Case Western Reserve University , Cleveland, Ohio , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheryl","family":"Cameron","sequence":"additional","affiliation":[{"name":"Department of Nutrition, Case Western Reserve University , Cleveland, Ohio , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Gravenstein","sequence":"additional","affiliation":[{"name":"Division of Geriatrics and Palliative Medicine, Warren Alpert Medical School, Brown University , Providence, Rhode Island , USA"},{"name":"Center on Innovation in Long-Term Services and Supports, Providence Veterans Administration Medical Center , Providence, Rhode Island , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5503-7888","authenticated-orcid":false,"given":"David H","family":"Canaday","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease, Case Western Reserve University School of Medicine , Cleveland, Ohio , USA"},{"name":"Geriatric Research, Education, and Clinical Center, Louis Stokes Veterans Affairs Northeast Ohio Healthcare System , Cleveland, Ohio , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,5,14]]},"reference":[{"key":"2024092316163303800_jiae234-B1","author":"Centers for Disease Control and Prevention"},{"key":"2024092316163303800_jiae234-B2","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1016\/j.jmii.2022.09.004","article-title":"Evaluation of the T cell and B cell response following the administration of COVID-19 vaccines in Korea","volume":"55","author":"Widyasari","year":"2022","journal-title":"J Microbiol Immunol Infect"},{"key":"2024092316163303800_jiae234-B3","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1038\/s41564-021-01046-z","article-title":"Induction of robust cellular and humoral immunity against SARS-CoV-2 after a third dose of BNT162b2 vaccine in previously unresponsive older adults","volume":"7","author":"Romero-Olmedo","year":"2022","journal-title":"Nat Microbiol"},{"key":"2024092316163303800_jiae234-B4","doi-asserted-by":"crossref","first-page":"100716","DOI":"10.1016\/j.xcrm.2022.100716","article-title":"Protective antibodies and T cell responses to Omicron variant after the booster dose of BNT162b2 vaccine","volume":"3","author":"Naaber","year":"2022","journal-title":"Cell Reports Med"},{"key":"2024092316163303800_jiae234-B5","doi-asserted-by":"crossref","first-page":"1035344","DOI":"10.3389\/fimmu.2022.1035344","article-title":"Three doses of BNT162b2 COVID-19 mRNA vaccine establish long-lasting CD8+ T cell immunity in CLL and MDS patients","volume":"13","author":"Hernandez","year":"2023","journal-title":"Front Immunol"},{"key":"2024092316163303800_jiae234-B6","doi-asserted-by":"crossref","first-page":"eadd3899","DOI":"10.1126\/sciimmunol.add3899","article-title":"Durable spike-specific T cell responses after different COVID-19 vaccination regimens are not further enhanced by booster vaccination","volume":"7","author":"Maringer","year":"2022","journal-title":"Sci Immunol"},{"key":"2024092316163303800_jiae234-B7","doi-asserted-by":"crossref","first-page":"2104","DOI":"10.4049\/jimmunol.2200525","article-title":"Memory B cells and memory T cells induced by SARS-CoV-2 booster vaccination or infection show different dynamics and responsiveness to the Omicron variant","volume":"209","author":"Mise-Omata","year":"2022","journal-title":"J Immunol"},{"key":"2024092316163303800_jiae234-B8","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.3904\/kjim.2022.173","article-title":"Comparison of the rapidity of SARS-CoV-2 immune responses between primary and booster vaccination for COVID-19","volume":"37","author":"Kim","year":"2022","journal-title":"Korean J Intern Med"},{"key":"2024092316163303800_jiae234-B9","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.jamda.2022.11.024","article-title":"T-cell mediated response after primary and booster SARS-CoV-2 messenger RNA vaccination in nursing home residents","volume":"24","author":"Schiavoni","year":"2023","journal-title":"J Am Med Dir Assoc"},{"key":"2024092316163303800_jiae234-B10","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1016\/j.cell.2020.09.038","article-title":"Antigen-specific adaptive immunity to SARS-CoV-2 in acute COVID-19 and associations with age and disease severity","volume":"183","author":"Rydyznski Moderbacher","year":"2020","journal-title":"Cell"},{"key":"2024092316163303800_jiae234-B11","doi-asserted-by":"crossref","first-page":"101","DOI":"10.3390\/vaccines11010101","article-title":"Updated insights into the T cell-mediated immune response against SARS-CoV-2: a step towards efficient and reliable vaccines","volume":"11","author":"Dhawan","year":"2023","journal-title":"Vaccines"},{"key":"2024092316163303800_jiae234-B12","doi-asserted-by":"crossref","first-page":"778679","DOI":"10.3389\/fimmu.2021.778679","article-title":"Impaired functional T-cell response to SARS-CoV-2 after two doses of BNT162b2 mRNA vaccine in older people","volume":"12","author":"Demaret","year":"2021","journal-title":"Front Immunol"},{"key":"2024092316163303800_jiae234-B13","doi-asserted-by":"crossref","first-page":"2112","DOI":"10.1093\/cid\/ciab447","article-title":"Reduced BNT162b2 messenger RNA vaccine response in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-naive nursing home residents","volume":"73","author":"Canaday","year":"2021","journal-title":"Clin Infect Dis"},{"key":"2024092316163303800_jiae234-B14","doi-asserted-by":"crossref","first-page":"e161045","DOI":"10.1172\/jci.insight.161045","article-title":"Immune defects associated with lower SARS-CoV-2 BNT162b2 mRNA vaccine response in elderly people","volume":"7","author":"Vitall\u00e9","year":"2022","journal-title":"JCI Insight"},{"key":"2024092316163303800_jiae234-B15","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1038\/s43587-022-00343-4","article-title":"Impaired CD4+ T cell response in older adults is associated with reduced immunogenicity and reactogenicity of mRNA COVID-19 vaccination","volume":"3","author":"Jo","year":"2023","journal-title":"Nat Aging"},{"key":"2024092316163303800_jiae234-B16","doi-asserted-by":"crossref","first-page":"104066","DOI":"10.1016\/j.ebiom.2022.104066","article-title":"COVID-19 vaccine booster dose needed to achieve Omicron-specific neutralisation in nursing home residents","volume":"80","author":"Canaday","year":"2022","journal-title":"EBioMedicine"},{"key":"2024092316163303800_jiae234-B17","doi-asserted-by":"crossref","first-page":"e2124331","DOI":"10.1001\/jamanetworkopen.2021.24331","article-title":"Comparison of SARS-CoV-2 antibody response by age among recipients of the BNT162b2 vs the mRNA-1273 vaccine","volume":"4","author":"Richards","year":"2021","journal-title":"JAMA Netw Open"},{"key":"2024092316163303800_jiae234-B18","doi-asserted-by":"crossref","first-page":"e157990","DOI":"10.1172\/JCI157990","article-title":"SARS-CoV-2 infection and vaccination trigger longlived B and CD4+ T lymphocytes with implications for booster strategies","volume":"132","author":"Mazzoni","year":"2022","journal-title":"J Clin Invest"},{"key":"2024092316163303800_jiae234-B19","doi-asserted-by":"crossref","first-page":"981350","DOI":"10.3389\/fimmu.2022.981350","article-title":"Cellular and humoral immune responses and breakthrough infections after three SARS-CoV-2 mRNA vaccine doses","volume":"13","author":"Almendro-V\u00e1zquez","year":"2022","journal-title":"Front Immunol"},{"key":"2024092316163303800_jiae234-B20","doi-asserted-by":"crossref","first-page":"100385","DOI":"10.1016\/j.lanepe.2022.100385","article-title":"Immunogenicity of BNT162b2 vaccine booster against SARS-CoV-2 Delta and Omicron variants in nursing home residents: a prospective observational study in older adults aged from 68 to 98 years","volume":"17","author":"Alidjinou","year":"2022","journal-title":"Lancet Reg Health Eur"},{"key":"2024092316163303800_jiae234-B21","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1038\/s41590-022-01184-4","article-title":"SARS-CoV-2 antigen exposure history shapes phenotypes and specificity of memory CD8+ T cells","volume":"23","author":"Minervina","year":"2022","journal-title":"Nat Immunol"},{"key":"2024092316163303800_jiae234-B22","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.cellimm.2009.04.002","article-title":"Increased per cell IFN-gamma productivity indicates recent in vivo activation of T cells","volume":"258","author":"Schlingmann","year":"2009","journal-title":"Cell Immunol"},{"key":"2024092316163303800_jiae234-B23","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.cmi.2021.09.031","article-title":"Immunological response against SARS-CoV-2 following full-dose administration of Comirnaty\u00ae COVID-19 vaccine in nursing home residents","volume":"28","author":"Albert","year":"2022","journal-title":"Clin Microbiol Infect"},{"key":"2024092316163303800_jiae234-B24","doi-asserted-by":"crossref","first-page":"e0249521","DOI":"10.1128\/spectrum.02495-21","article-title":"Humoral and cellular immune responses to vector, mix-and-match, or mRNA vaccines against SARS-CoV-2 and the relationship between the two immune responses","volume":"10","author":"Nam","year":"2022","journal-title":"Microbiol Spectr"},{"key":"2024092316163303800_jiae234-B25","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s12979-023-00327-x","article-title":"Frailty impacts immune responses to Moderna COVID-19 mRNA vaccine in older adults","volume":"20","author":"Semelka","year":"2023","journal-title":"Immun Ageing"},{"key":"2024092316163303800_jiae234-B26","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1038\/s43587-022-00292-y","article-title":"Signs of immunosenescence correlate with poor outcome of mRNA COVID-19 vaccination in older adults","volume":"2","author":"Palacios-Pedrero","year":"2022","journal-title":"Nat Aging"},{"key":"2024092316163303800_jiae234-B27","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1016\/S1473-3099(22)00143-8","article-title":"Risk of SARS-CoV-2 reinfection and COVID-19 hospitalisation in individuals with natural and hybrid immunity: a retrospective, total population cohort study in Sweden","volume":"22","author":"Nordstr\u00f6m","year":"2022","journal-title":"Lancet Infect Dis"},{"key":"2024092316163303800_jiae234-B28","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1016\/j.jiph.2023.06.003","article-title":"Outcomes associated with SARS-CoV-2 reinfection in individuals with natural and hybrid immunity","volume":"16","author":"Suleyman","year":"2023","journal-title":"J Infect Public Health"},{"key":"2024092316163303800_jiae234-B29","doi-asserted-by":"crossref","first-page":"530","DOI":"10.3390\/biomedicines9050530","article-title":"Non-immunotherapy application of LNP-mRNA: maximizing efficacy and safety","volume":"9","author":"Vlatkovic","year":"2021","journal-title":"Biomedicines"},{"key":"2024092316163303800_jiae234-B30","doi-asserted-by":"crossref","first-page":"174548","DOI":"10.1016\/j.ejphar.2021.174548","article-title":"Sex-related susceptibility in coronavirus disease 2019 (COVID-19): proposed mechanisms","volume":"912","author":"Aksoyalp","year":"2021","journal-title":"Eur J Pharmacol. Netherlands"},{"key":"2024092316163303800_jiae234-B31","doi-asserted-by":"crossref","first-page":"e2111398","DOI":"10.1001\/jamanetworkopen.2021.11398","article-title":"Association of circulating sex hormones with inflammation and disease severity in patients with COVID-19","volume":"4","author":"Dhindsa","year":"2021","journal-title":"JAMA Netw Open"},{"key":"2024092316163303800_jiae234-B32","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1038\/s41541-021-00412-6","article-title":"Sex-specific effects of aging on humoral immune responses to repeated influenza vaccination in older adults","volume":"6","author":"Shapiro","year":"2021","journal-title":"NPJ Vaccines"},{"key":"2024092316163303800_jiae234-B33","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1177\/0192623308320279","article-title":"Characterization of age- and gender-related changes in the spleen and thymus from control cynomolgus macaques used in toxicity studies","volume":"36","author":"Spoor","year":"2008","journal-title":"Toxicol Pathol"},{"key":"2024092316163303800_jiae234-B34","doi-asserted-by":"crossref","first-page":"20376","DOI":"10.1038\/s41598-022-24938-4","article-title":"Early CD4+ T cell responses induced by the BNT162b2 SARS-CoV-2 mRNA vaccine predict immunological memory","volume":"12","author":"Bai","year":"2022","journal-title":"Sci Rep"},{"key":"2024092316163303800_jiae234-B35","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1016\/j.immuni.2020.10.006","article-title":"Unbiased screens show CD8+ T cells of COVID-19 patients recognize shared epitopes in SARS-CoV-2 that largely reside outside the spike protein","volume":"53","author":"Ferretti","year":"2020","journal-title":"Immunity"},{"key":"2024092316163303800_jiae234-B36","doi-asserted-by":"crossref","first-page":"e188","DOI":"10.1016\/S2666-7568(23)00055-7","article-title":"Determinants of humoral and cellular immune responses to three doses of mRNA SARS-CoV-2 vaccines in older adults: a longitudinal cohort study","volume":"4","author":"Ravussin","year":"2023","journal-title":"Lancet Healthy Longev"},{"key":"2024092316163303800_jiae234-B37","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1038\/s41591-022-01700-x","article-title":"Ancestral SARS-CoV-2-specific T cells cross-recognize the Omicron variant","volume":"28","author":"Gao","year":"2022","journal-title":"Nat Med"},{"key":"2024092316163303800_jiae234-B38","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1016\/j.cell.2022.01.015","article-title":"SARS-CoV-2 vaccination induces immunological T cell memory able to cross-recognize variants from Alpha to Omicron","volume":"185","author":"Tarke","year":"2022","journal-title":"Cell"},{"key":"2024092316163303800_jiae234-B39","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1016\/j.jinf.2021.10.026","article-title":"Evolution of SARS-CoV-2 immune responses in nursing home residents following full dose of the Comirnaty\u00ae COVID-19 vaccine","volume":"84","author":"Gim\u00e9nez","year":"2022","journal-title":"J Infect"}],"container-title":["The Journal of Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jid\/advance-article-pdf\/doi\/10.1093\/infdis\/jiae234\/58445048\/jiae234.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jid\/article-pdf\/230\/3\/635\/59248700\/jiae234.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jid\/article-pdf\/230\/3\/635\/59248700\/jiae234.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,23]],"date-time":"2024-09-23T16:17:02Z","timestamp":1727108222000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jid\/article\/230\/3\/635\/7672966"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,14]]},"references-count":39,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,5,14]]},"published-print":{"date-parts":[[2024,9,23]]}},"URL":"https:\/\/doi.org\/10.1093\/infdis\/jiae234","relation":{},"ISSN":["0022-1899","1537-6613"],"issn-type":[{"value":"0022-1899","type":"print"},{"value":"1537-6613","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,9,15]]},"published":{"date-parts":[[2024,5,14]]}}}