{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T15:58:40Z","timestamp":1753891120125,"version":"3.41.2"},"reference-count":81,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T00:00:00Z","timestamp":1675296000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007833","name":"Hamad Medical Corporation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007833","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>The BNT162b2 mRNA-based vaccine has shown high efficacy in preventing COVID-19 infection but there are limited data on the types and persistence of the humoral and T cell responses to such a vaccine.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Here, we dissect the vaccine-induced humoral and cellular responses in a cohort of six healthy recipients of two doses of this vaccine.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results and discussion<\/jats:title><jats:p>Overall, there was heterogeneity in the spike-specific humoral and cellular responses among vaccinated individuals. Interestingly, we demonstrated that anti-spike antibody levels detected by a novel simple automated assay (Jess) were strongly correlated (r=0.863, P&amp;lt;0.0001) with neutralizing activity; thus, providing a potential surrogate for neutralizing cell-based assays. The spike-specific T cell response was measured with a newly modified T-spot assay in which the high-homology peptide-sequences cross-reactive with other coronaviruses were removed. This response was induced in 4\/6 participants after the first dose, and all six participants after the second dose, and remained detectable in 4\/6 participants five months post-vaccination. We have also shown for the first time, that BNT162b2 vaccine enhanced T cell responses also against known human common viruses. In addition, we demonstrated the efficacy of a rapid ex-vivo T cell expansion protocol for spike-specific T cell expansion to be potentially used for adoptive-cell therapy in severe COVID-19, immunocompromised individuals, and other high-risk groups. There was a 9 to 13.7-fold increase in the number of expanded T cells with a significant increase of anti-spike specific response showing higher frequencies of both activation and cytotoxic markers. Interestingly, effector memory T cells were dominant in all four participants\u2019 CD8+ expanded memory T cells; CD4+ T cells were dominated by effector memory in 2\/4 participants and by central memory in the remaining two participants. Moreover, we found that high frequencies of CD4+ terminally differentiated memory T cells were associated with a greater reduction of spike-specific activated CD4+ T cells. Finally, we showed that participants who had a CD4+ central memory T cell dominance expressed a high CD69 activation marker in the CD4+ activated T cells.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2023.1061255","type":"journal-article","created":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T17:36:07Z","timestamp":1675359367000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Persistence of spike-specific immune responses in BNT162b2-vaccinated donors and generation of rapid ex-vivo T cells expansion protocol for adoptive immunotherapy: A pilot study"],"prefix":"10.3389","volume":"14","author":[{"given":"Sarra","family":"Mestiri","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maysaloun","family":"Merhi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Varghese P.","family":"Inchakalody","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nassiba","family":"Taib","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria K.","family":"Smatti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fareed","family":"Ahmad","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Afsheen","family":"Raza","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fatma H.","family":"Ali","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shereena","family":"Hydrose","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Queenie","family":"Fernandes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abdul W.","family":"Ansari","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fairooz","family":"Sahir","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lobna","family":"Al-Zaidan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Munir","family":"Jalis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mokhtar","family":"Ghoul","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Niloofar","family":"Allahverdi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammed U.","family":"Al Homsi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shahab","family":"Uddin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew Martin","family":"Jeremijenko","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mai","family":"Nimir","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laith J.","family":"Abu-Raddad","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fatma Ben","family":"Abid","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahmed","family":"Zaqout","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sameer R.","family":"Alfheid","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hassan Mohamed Hassan","family":"Saqr","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ali S.","family":"Omrani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ali Ait","family":"Hssain","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muna","family":"Al Maslamani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hadi M.","family":"Yassine","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Said","family":"Dermime","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,2,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1080\/07853890.2022.2031274","article-title":"Emerging COVID-19 variants and their impact on SARS-CoV-2 diagnosis, therapeutics and vaccines","volume":"54","author":"Fernandes","year":"2022","journal-title":"Ann Med"},{"key":"B2","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1007\/s40265-021-01480-7","article-title":"BNT162b2 mRNA COVID-19 vaccine: First approval","volume":"81","author":"Lamb","year":"2021","journal-title":"Drugs"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc2036242","article-title":"Safety and efficacy of the BNT162b2 mRNA covid-19 vaccine","volume":"384","author":"Skowronski","year":"2021","journal-title":"New Engl J Med"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2101765","article-title":"BNT162b2 mRNA covid-19 vaccine in a nationwide mass vaccination setting","volume":"384","author":"Dagan","year":"2021","journal-title":"New Engl J Med"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-021-01377-8","article-title":"Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection","volume":"27","author":"Khoury","year":"2021","journal-title":"Nat Med"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/S2666-5247(21)00267-6","article-title":"Neutralising antibody titres as predictors of protection against SARS-CoV-2 variants and the impact of boosting: a meta-analysis","volume":"3","author":"Cromer","year":"2022","journal-title":"Lancet Microbe"},{"key":"B7","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1186\/s12916-022-02249-9","article-title":"Prediction of long-term kinetics of vaccine-elicited neutralizing antibody and time-varying vaccine-specific efficacy against the SARS-CoV-2 delta variant by clinical endpoint","volume":"20","author":"Chen","year":"2022","journal-title":"BMC Med"},{"key":"B8","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1186\/s12985-021-01490-7","article-title":"Evaluation of SARS-CoV-2 neutralizing antibodies using a vesicular stomatitis virus possessing SARS-CoV-2 spike protein","volume":"18","author":"Tani","year":"2021","journal-title":"Virol J"},{"key":"B9","doi-asserted-by":"publisher","first-page":"iqab005","DOI":"10.1093\/oxfimm\/iqab005","article-title":"The role of pseudotype neutralization assays in understanding SARS CoV-2","volume":"2","author":"Cantoni","year":"2021","journal-title":"Oxford Open Immunol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0262657","article-title":"Development and utilization of a surrogate SARS-CoV-2 viral neutralization assay to assess mRNA vaccine responses","volume":"17","author":"Wisnewski","year":"2022","journal-title":"PLos One"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.142362","article-title":"A simple protein-based surrogate neutralization assay for SARS-CoV-2","volume":"5","author":"Abe","year":"2020","journal-title":"JCI Insight"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1128\/mSphere.00802-20","article-title":"Competitive SARS-CoV-2 serology reveals most antibodies targeting the spike receptor-binding domain compete for ACE2 binding","volume":"5","author":"Byrnes","year":"2020","journal-title":"mSphere"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-020-0631-z","article-title":"A SARS-CoV-2 surrogate virus neutralization test based on antibody-mediated blockage of ACE2-spike protein-protein interaction","volume":"38","author":"Tan","year":"2020","journal-title":"Nat Biotechnol"},{"key":"B14","doi-asserted-by":"publisher","first-page":"123409","DOI":"10.1016\/j.talanta.2022.123409","article-title":"Review of COVID-19 testing and diagnostic methods","volume":"244","author":"Filchakova","year":"2022","journal-title":"Talanta"},{"key":"B15","unstructured":"Rapid characterization of human immune response to SARS-CoV-2 antigens using simple Western2022"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1007\/s10096-021-04203-8","article-title":"Automated Western immunoblotting detection of anti-SARS-CoV-2 serum antibodies","volume":"40","author":"Edouard","year":"2021","journal-title":"Eur J Clin Microbiol Infect Dis"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1101\/2022.01.20.477038","article-title":"Evidence of antibodies against SARS-CoV-2 in wild mustelids from Brittany (France)","volume":"69","author":"Davoust","year":"2022","journal-title":"Transboundary emerging Dis"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.748291","article-title":"Analysis of serological biomarkers of SARS-CoV-2 infection in convalescent samples from severe, moderate and mild COVID-19 cases","volume":"12","author":"Castillo-Olivares","year":"2021","journal-title":"Front Immunol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"100293","DOI":"10.1016\/j.onehlt.2021.100293","article-title":"SARS-CoV-2 antibodies seroprevalence in dogs from France using ELISA and an automated western blotting assay","volume":"13","author":"Laidoudi","year":"2021","journal-title":"One Health (Amsterdam Netherlands)"},{"key":"B20","doi-asserted-by":"publisher","first-page":"102725","DOI":"10.1016\/j.msard.2020.102725","article-title":"COVID-19 in ocrelizumab-treated people with multiple sclerosis","volume":"49","author":"Hughes","year":"2021","journal-title":"Multiple sclerosis related Disord"},{"key":"B21","doi-asserted-by":"publisher","first-page":"103078","DOI":"10.1016\/j.isci.2021.103078","article-title":"Development of humoral and cellular immunological memory against SARS-CoV-2 despite b cell depleting treatment in multiple sclerosis","volume":"24","author":"Asplund H\u00f6gelin","year":"2021","journal-title":"iScience"},{"key":"B22","doi-asserted-by":"publisher","first-page":"102185","DOI":"10.1016\/j.msard.2020.102185","article-title":"Anti-CD20 and COVID-19 in multiple sclerosis and related disorders: A case series of 60 patients from Madrid, Spain","volume":"42","author":"Montero-Escribano","year":"2020","journal-title":"Multiple sclerosis related Disord"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.869990","article-title":"Long-lasting T cell responses in BNT162b2 COVID-19 mRNA vaccinees and COVID-19 convalescent patients","volume":"13","author":"Hurme","year":"2022","journal-title":"Front Immunol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"6687","DOI":"10.1038\/s41598-022-07741-z","article-title":"Persistent spike-specific T cell immunity despite antibody reduction after 3 months from SARS-CoV-2 BNT162b2-mRNA vaccine","volume":"12","author":"Agrati","year":"2022","journal-title":"Sci Rep"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.832106","article-title":"Conservation and evolution of antigenic determinants of SARS-CoV-2: An insight for immune escape and vaccine design","volume":"13","author":"Jaiswal","year":"2022","journal-title":"Front Immunol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-022-00838-5","article-title":"T Cell epitopes in SARS-CoV-2 proteins are substantially conserved in the omicron variant","volume":"19","author":"Choi","year":"2022","journal-title":"Cell Mol Immunol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.72619","article-title":"mRNA vaccine-induced T cells respond identically to SARS-CoV-2 variants of concern but differ in longevity and homing properties depending on prior infection status","volume":"10","author":"Neidleman","year":"2021","journal-title":"eLife"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.665329","article-title":"Impaired cytotoxic response in PBMCs from patients with COVID-19 admitted to the ICU: Biomarkers to predict disease severity","volume":"12","author":"Vig\u00f3n","year":"2021","journal-title":"Front Immunol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abe4782","article-title":"Severely ill COVID-19 patients display impaired exhaustion features in SARS-CoV-2-reactive CD8(+) T cells","volume":"6","author":"Kusnadi","year":"2021","journal-title":"Sci Immunol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00827","article-title":"Reduction and functional exhaustion of T cells in patients with coronavirus disease 2019 (COVID-19)","volume":"11","author":"Diao","year":"2020","journal-title":"Front Immunol"},{"key":"B31","doi-asserted-by":"publisher","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":"B32","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2021013429","article-title":"Severe impairment of T-cell responses to BNT162b2 immunization in patients with multiple myeloma","volume":"139","author":"En\u00dfle","year":"2022","journal-title":"Blood"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.26508\/lsa.202201381","article-title":"mRNA COVID-19 vaccine booster fosters b- and T-cell responses in immunocompromised patients","volume":"5","author":"Azzolini","year":"2022","journal-title":"Life Sci alliance"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.jviromet.2010.08.006","article-title":"Generation of VSV pseudotypes using recombinant \u0394G-VSV for studies on virus entry, identification of entry inhibitors, and immune responses to vaccines","volume":"169","author":"Whitt","year":"2010","journal-title":"J virological Methods"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2012.130","article-title":"Rapidly generated multivirus-specific cytotoxic T lymphocytes for the prophylaxis and treatment of viral infections","volume":"20","author":"Gerdemann","year":"2012","journal-title":"Mol Ther"},{"key":"B36","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1186\/s13073-018-0568-8","article-title":"Human genetic variants and age are the strongest predictors of humoral immune responses to common pathogens and vaccines","volume":"10","author":"Scepanovic","year":"2018","journal-title":"Genome Med"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2016.08.002","article-title":"Shaping variation in the human immune system","volume":"37","author":"Liston","year":"2016","journal-title":"Trends Immunol"},{"key":"B38","doi-asserted-by":"publisher","first-page":"907","DOI":"10.1038\/s41467-022-28527-x","article-title":"Population antibody responses following COVID-19 vaccination in 212,102 individuals","volume":"13","author":"Ward","year":"2022","journal-title":"Nat Commun"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines10020171","article-title":"Overview of anti-SARS-CoV-2 immune response six months after BNT162b2 mRNA vaccine","volume":"10","author":"Gandolfo","year":"2022","journal-title":"Vaccines"},{"key":"B40","doi-asserted-by":"publisher","first-page":"100208","DOI":"10.1016\/j.lanepe.2021.100208","article-title":"Dynamics of antibody response to BNT162b2 vaccine after six months: a longitudinal prospective study","volume":"10","author":"Naaber","year":"2021","journal-title":"Lancet regional Health Europe"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.3390\/v14020312","article-title":"Differential dynamics of SARS-CoV-2 binding and functional antibodies upon BNT162b2 vaccine: A 6-month follow-up","volume":"14","author":"Matusali","year":"2022","journal-title":"Viruses"},{"key":"B42","doi-asserted-by":"publisher","first-page":"3936","DOI":"10.1016\/j.cell.2021.06.005","article-title":"SARS-CoV-2 mRNA vaccination induces functionally diverse antibodies to NTD, RBD, and S2","volume":"184","author":"Amanat","year":"2021","journal-title":"Cell"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.808932","article-title":"Spike-dependent opsonization indicates both dose-dependent inhibition of phagocytosis and that non-neutralizing antibodies can confer protection to SARS-CoV-2","volume":"12","author":"Bahnan","year":"2021","journal-title":"Front Immunol"},{"key":"B44","doi-asserted-by":"publisher","first-page":"110368","DOI":"10.1016\/j.celrep.2022.110368","article-title":"A fc-enhanced NTD-binding non-neutralizing antibody delays virus spread and synergizes with a nAb to protect mice from lethal SARS-CoV-2 infection","volume":"38","author":"Beaudoin-Bussi\u00e8res","year":"2022","journal-title":"Cell Rep"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.909910","article-title":"IgG anti-spike antibodies and surrogate neutralizing antibody levels decline faster 3 to 10 months after BNT162b2 vaccination than after SARS-CoV-2 infection in healthcare workers","volume":"13","author":"Decru","year":"2022","journal-title":"Front Immunol"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciab607","article-title":"Long-term persistence of spike protein antibody and predictive modeling of antibody dynamics after infection with severe acute respiratory syndrome coronavirus 2","volume":"74","author":"Grandjean","year":"2022","journal-title":"Clin Infect Dis an Off Publ Infect Dis Soc America"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1126\/science.abh1282","article-title":"Prior SARS-CoV-2 infection rescues b and T cell responses to variants after first vaccine dose","volume":"372","author":"Reynolds","year":"2021","journal-title":"Sci (New York NY)"},{"key":"B48","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1126\/science.abd3871","article-title":"Selective and cross-reactive SARS-CoV-2 T cell epitopes in unexposed humans","volume":"370","author":"Mateus","year":"2020","journal-title":"Sci (New York NY)"},{"volume-title":"SARS-CoV-2 presents amino acid sequences, analogous to those of the Epstein-Barr virus - human gammaherpesvirus 4","year":"2020","author":"Geraldes","key":"B49"},{"key":"B50","doi-asserted-by":"publisher","first-page":"103705","DOI":"10.1016\/j.ebiom.2021.103705","article-title":"Safety and efficacy of the mRNA BNT162b2 vaccine against SARS-CoV-2 in five groups of immunocompromised patients and healthy controls in a prospective open-label clinical trial","volume":"74","author":"Bergman","year":"2021","journal-title":"EBioMedicine"},{"key":"B51","unstructured":"Immunocompromised populations and the risk of viral variants2022"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.27643","article-title":"The emergence and epidemic characteristics of the highly mutated SARS-CoV-2 omicron variant","volume":"94","author":"Tian","year":"2022","journal-title":"J Med virology"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019000924","article-title":"Virus-specific T-cell therapies for patients with primary immune deficiency","volume":"135","author":"Keller","year":"2020","journal-title":"Blood"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.5.2888","article-title":"CD4 T cell-mediated protection from lethal influenza: perforin and antibody-mediated mechanisms give a one-two punch","volume":"177","author":"Brown","year":"2006","journal-title":"J Immunol (Baltimore Md 1950)"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01049-10","article-title":"T Cell responses are required for protection from clinical disease and for virus clearance in severe acute respiratory syndrome coronavirus-infected mice","volume":"84","author":"Zhao","year":"2010","journal-title":"J virology"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2016.05.006","article-title":"Airway memory CD4(+) T cells mediate protective immunity against emerging respiratory coronaviruses","volume":"44","author":"Zhao","year":"2016","journal-title":"Immunity"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v10.i2.260","article-title":"Long-term persistence of T cell memory to HBsAg after hepatitis b vaccination","volume":"10","author":"Wang","year":"2004","journal-title":"World J gastroenterology"},{"key":"B58","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1007\/s00281-006-0027-2","article-title":"Generation and maintenance of human memory cells during viral infection","volume":"28","author":"Halwani","year":"2006","journal-title":"Springer Semin immunopathology"},{"key":"B59","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1007\/978-1-4419-6451-9_8","article-title":"Longevity of T-cell memory following acute viral infection","volume":"684","author":"Walker","year":"2010","journal-title":"Adv Exp Med Biol"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00171","article-title":"T Cell responses to viral infections - opportunities for peptide vaccination","volume":"5","author":"Rosendahl Huber","year":"2014","journal-title":"Front Immunol"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.02243-20","article-title":"Impaired cytotoxic CD8(+) T cell response in elderly COVID-19 patients","volume":"11","author":"Westmeier","year":"2020","journal-title":"mBio"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-0995-0","article-title":"Humoral and circulating follicular helper T cell responses in recovered patients with COVID-19","volume":"26","author":"Juno","year":"2020","journal-title":"Nat Med"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-021-01329-2","article-title":"Single-cell multi-omics analysis of the immune response in COVID-19","volume":"27","author":"Stephenson","year":"2021","journal-title":"Nat Med"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2038","article-title":"Origins of CD4(+) effector and central memory T cells","volume":"12","author":"Pepper","year":"2011","journal-title":"Nat Immunol"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.22.012703.104702","article-title":"Central memory and effector memory T cell subsets: function, generation, and maintenance","volume":"22","author":"Sallusto","year":"2004","journal-title":"Annu Rev Immunol"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1016\/S0264-410X(02)00407-3","article-title":"Memory T cells and vaccines","volume":"21","author":"Esser","year":"2003","journal-title":"Vaccine"},{"key":"B67","doi-asserted-by":"publisher","first-page":"103409","DOI":"10.1016\/j.ebiom.2021.103409","article-title":"Senescent T cells: a potential biomarker and target for cancer therapy","volume":"68","author":"Zhang","year":"2021","journal-title":"EBioMedicine"},{"key":"B68","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1615\/CritRevImmunol.v23.i12.30","article-title":"CD8 T cells and aging","volume":"23","author":"Effros","year":"2003","journal-title":"Crit Rev Immunol"},{"key":"B69","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.imlet.2006.07.006","article-title":"Age-associated changes within CD4+ T cells","volume":"107","author":"Kovaiou","year":"2006","journal-title":"Immunol letters"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.1.212","article-title":"Memory T cells constitute a subset of the human CD8+CD45RA+ pool with distinct phenotypic and migratory characteristics","volume":"167","author":"Faint","year":"2001","journal-title":"J Immunol (Baltimore Md 1950)"},{"key":"B71","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1111\/j.0105-2896.2005.00245.x","article-title":"Rheumatoid arthritis","volume":"204","author":"Goronzy","year":"2005","journal-title":"Immunol Rev"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1186\/ar1452","article-title":"Interleukin-7 deficiency in rheumatoid arthritis: consequences for therapy-induced lymphopenia","volume":"7","author":"Ponchel","year":"2005","journal-title":"Arthritis Res Ther"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1038\/nri1254","article-title":"Human CD8(+) T-cell differentiation in response to viruses","volume":"3","author":"van Lier","year":"2003","journal-title":"Nat Rev Immunol"},{"key":"B74","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1146\/annurev.immunol.25.022106.141553","article-title":"Cellular responses to viral infection in humans: lessons from Epstein-Barr virus","volume":"25","author":"Hislop","year":"2007","journal-title":"Annu Rev Immunol"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1016\/j.humimm.2004.02.014","article-title":"CD8(+) T-cell immunity to cytomegalovirus","volume":"65","author":"Moss","year":"2004","journal-title":"Hum Immunol"},{"key":"B76","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1186\/s12979-019-0164-9","article-title":"Immunosenescence and human vaccine immune responses","volume":"16","author":"Crooke","year":"2019","journal-title":"Immun Ageing I A"},{"key":"B77","doi-asserted-by":"publisher","first-page":"103998","DOI":"10.1016\/j.cellimm.2019.103998","article-title":"Aging and influenza vaccine-induced immunity","volume":"348","author":"Dugan","year":"2020","journal-title":"Cell Immunol"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines10040607","article-title":"Immunosenescence and altered vaccine efficiency in older subjects: A myth difficult to change","volume":"10","author":"Fulop","year":"2022","journal-title":"Vaccines"},{"key":"B79","doi-asserted-by":"publisher","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":"B80","doi-asserted-by":"publisher","DOI":"10.1080\/21645515.2020.1750249","article-title":"Early drop of circulating T cells negatively correlates with the protective immune response to yellow fever vaccination","volume":"16","author":"Bovay","year":"2020","journal-title":"Hum Vaccines immunotherapeutics"},{"key":"B81","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.1204616109","article-title":"CD69 guides CD4+ T cells to the seat of memory","volume-title":"Proceedings of the National Academy of Sciences of the United States of America","author":"Schoenberger","year":"2012"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1061255\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T17:36:15Z","timestamp":1675359375000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1061255\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,2]]},"references-count":81,"alternative-id":["10.3389\/fimmu.2023.1061255"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2023.1061255","relation":{},"ISSN":["1664-3224"],"issn-type":[{"type":"electronic","value":"1664-3224"}],"subject":[],"published":{"date-parts":[[2023,2,2]]},"article-number":"1061255"}}