{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T20:07:33Z","timestamp":1791230853403,"version":"4.1.0"},"reference-count":26,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T00:00:00Z","timestamp":1752710400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Inactivated COVID-19 vaccines exhibit more rapid declines in antibody levels than other vaccine platforms, likely owing to transient antigen exposure and limited germinal center persistence. Moreover, although homologous boosting effectively restores humoral immunity, concerns persist regarding potential T cell exhaustion with repeated antigen exposure. We evaluated the effectiveness of delayed homologous CoronaVac booster immunization in reactivating immune memory.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A prospective longitudinal cohort study was conducted with 83 healthy adults who received two CoronaVac vaccine doses (14-day interval) and a homologous booster shot after 12 months. Peripheral blood samples were collected 0, 3, 7, 10, and 14 days after booster vaccination. Neutralizing antibodies were analysed using live-virus microneutralization assays. Anti-receptor-binding domain immunoglobulin subclasses (IgG1, IgG2, IgG3, IgG4) were detected using enzyme-linked immunosorbent assay. Cytokine secretion (interferon [IFN]-\u03b3\/interleukin [IL]-2\/IL-4\/IL-5) was assessed using enzyme-linked immunospot assay. T cell polarization and exhaustion markers (T-bet\/GATA3 and CD69\/CTLA-4\/PD-1) were evaluated using flow cytometry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The geometric mean titer of neutralizing antibodies reached 254.5 on day 14. The initial immune response was dominated by IgG3, which subsequently shifted to IgG1. A significant Th1-type cellular immune response was characterized by increased IFN-\u03b3 and IL-2 secretion, and upregulated T-bet expression. Transient CD69+ T cell activation occurred between days 3 and 10 without sustained PD-1 and CTLA-4 elevation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Delayed homologous CoronaVac booster immunization effectively reactivates immune memory, facilitated by Th1 polarization and transient T cell activation, which do not result in T cell exhaustion. These findings suggest the potential application of long-interval immunization strategies against COVID-19.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1636629","type":"journal-article","created":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T05:25:28Z","timestamp":1752729928000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Immune memory reactivation and T cell dynamics following 12-month homologous CoronaVac booster: a longitudinal cohort study"],"prefix":"10.3389","volume":"16","author":[{"given":"Xinran","family":"Song","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weixin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Bai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Lv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiang","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,7,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1716","DOI":"10.1038\/s41467-024-45953-1","article-title":"Persistence in risk and effect of COVID-19 vaccination on long-term health consequences after SARS-CoV-2 infection","volume":"15","author":"Lam","year":"2024","journal-title":"Nat Commun"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2022.7493","article-title":"Association of prior BNT162b2 COVID-19 vaccination with symptomatic SARS-CoV-2 infection in children and adolescents during Omicron predominance","volume":"327","author":"Fleming-Dutra","year":"2022","journal-title":"JAMA"},{"key":"B3","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1080\/14760584.2024.2331065","article-title":"The durability of vaccine-induced protection: an\u00a0overview","volume":"23","author":"Vashishtha","year":"2024","journal-title":"Expert Rev Vaccines"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(22)00345-0","article-title":"Vaccine effectiveness of one, two, and three doses of BNT162b2 and CoronaVac against COVID-19 in Hong Kong: a population-based observational study","volume":"22","author":"McMenamin","year":"2022","journal-title":"Lancet Infect Dis"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03738-2","article-title":"SARS-CoV-2 mRNA vaccines induce persistent human germinal centre responses","volume":"596","author":"Turner","year":"2021","journal-title":"Nature"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciab823","article-title":"Safety and immunogenicity of an inactivated severe acute respiratory syndrome coronavirus 2 vaccine in a subgroup of healthy adults in Chile","volume":"75","author":"Bueno","year":"2021","journal-title":"Clin Infect Diseases"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.01311-22","article-title":"Inactivated vaccine-induced SARS-CoV-2 variant-specific immunity in children","volume":"13","author":"Soto","year":"2022","journal-title":"mBio"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2021.102298","article-title":"Th1 skewed immune response of whole virion inactivated SARS-CoV-2 vaccine and its safety evaluation","volume":"24","author":"Ganneru","year":"2021","journal-title":"iScience"},{"key":"B9","doi-asserted-by":"publisher","first-page":"6952","DOI":"10.1038\/s41467-022-34280-y","article-title":"Safety and immunogenicity following a homologous booster dose of CoronaVac in children and adolescents","volume":"13","author":"Wang","year":"2022","journal-title":"Nat Commun"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2021.10.006","article-title":"Dynamic SARS-CoV-2-specific B-cell and T-cell responses following immunization with an inactivated COVID-19 vaccine","volume":"28","author":"Chen","year":"2022","journal-title":"Clin Microbiol Infect"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1080\/14760584.2022.2071705","article-title":"Repeated vaccination and \u2018vaccine exhaustion\u2019: relevance to the COVID-19 crisis","volume":"21","author":"Azim Majumder","year":"2022","journal-title":"Expert Rev Vaccines"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2020.03.025","article-title":"Negative effect on immune response of repeated influenza vaccination and waning effectiveness in interseason for elderly people","volume":"38","author":"Sugishita","year":"2020","journal-title":"Vaccine"},{"key":"B13","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1038\/s41392-024-01867-4","article-title":"Initial COVID-19 severity influenced by SARS-CoV-2-specific T cells imprints T-cell memory and inversely affects reinfection","volume":"9","author":"Yang","year":"2024","journal-title":"Signal Transduct Target Ther"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.genrep.2023.101747","article-title":"Evaluation of T cell exhaustion based on the expression of EOMES, Tbet and co-inhibitory receptors in severe and non-severe COVID-19 patients","volume":"31","author":"Saeedifar","year":"2023","journal-title":"Gene Rep"},{"key":"B15","doi-asserted-by":"publisher","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":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(21)00070-0","article-title":"Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBV152: interim results from a double-blind, randomised, multicentre, phase 2 trial, and 3-month follow-up of a double-blind, randomised phase 1 trial","volume":"21","author":"Ella","year":"2021","journal-title":"Lancet Infect Dis"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.00181-22","article-title":"Status of Humoral and Cellular Immune Responses within 12 Months following CoronaVac Vaccination against COVID-19","volume":"13","author":"Zhao","year":"2022","journal-title":"mBio"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1111\/imm.13531","article-title":"The kinetics of IgG subclasses and contributions to neutralizing activity against SARS-CoV-2 wild-type strain and variants in healthy adults immunized with inactivated vaccine","volume":"167","author":"Chen","year":"2022","journal-title":"Immunology"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/s1473-3099(21)00319-4","article-title":"Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine (CoronaVac) in healthy children and adolescents: a double-blind, randomised, controlled, phase 1\/2 clinical trial","volume":"21","author":"Han","year":"2021","journal-title":"Lancet Infect Dis"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/s1473-3099(21)00681-2","article-title":"Immunogenicity and safety of a third dose of CoronaVac, and immune persistence of a two-dose schedule, in healthy adults: interim results from two single-centre, double-blind, randomised, placebo-controlled phase 2 clinical trials","volume":"22","author":"Zeng","year":"2022","journal-title":"Lancet Infect Dis"},{"key":"B21","doi-asserted-by":"publisher","first-page":"8054","DOI":"10.1038\/s41467-024-52470-8","article-title":"Sequence variants influencing the regulation of serum IgG subclass levels","volume":"15","author":"Olafsdottir","year":"2024","journal-title":"Nat Commun"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00740","article-title":"Fc\u03b3R Binding and ADCC activity of human IgG Allotypes","volume":"11","author":"de Taeye","year":"2020","journal-title":"Front Immunol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.ade2798","article-title":"Class switch toward noninflammatory, spike-specific IgG4 antibodies after repeated SARS-CoV-2 mRNA vaccination","volume":"8","author":"Irrgang","year":"2023","journal-title":"Sci Immunol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"228ra38","DOI":"10.1126\/scitranslmed.3007736","article-title":"Polyfunctional Fc-effector profiles mediated by IgG subclass selection distinguish RV144 and VAX003 vaccines","volume":"6","author":"Chung","year":"2014","journal-title":"Sci Transl Med"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.1530","article-title":"The roles of innate and adaptive immunity in inactivated viral vaccination-mediated protection against COVID-19","volume":"14","author":"Yu","year":"2024","journal-title":"Clin Transl Med"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2014.05.018","article-title":"Serial transfer of single-cell-derived immunocompetence reveals stemness of CD8(+) central memory T cells","volume":"41","author":"Graef","year":"2014","journal-title":"Immunity"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1636629\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T05:25:29Z","timestamp":1752729929000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1636629\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,17]]},"references-count":26,"alternative-id":["10.3389\/fimmu.2025.1636629"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1636629","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,17]]},"article-number":"1636629"}}