Immune memory reactivation and T cell dynamics following 12-month homologous CoronaVac booster: a longitudinal cohort study

BackgroundInactivated 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 rega...

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Main Authors: Xinran Song, Weixin Chen, Shuang Bai, Min Lv, Jian Wang, Ao Zhang, Jiang Wu, Wei Zhao
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-07-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1636629/full
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author Xinran Song
Xinran Song
Weixin Chen
Weixin Chen
Shuang Bai
Shuang Bai
Min Lv
Min Lv
Jian Wang
Jian Wang
Ao Zhang
Ao Zhang
Jiang Wu
Jiang Wu
Wei Zhao
Wei Zhao
Wei Zhao
author_facet Xinran Song
Xinran Song
Weixin Chen
Weixin Chen
Shuang Bai
Shuang Bai
Min Lv
Min Lv
Jian Wang
Jian Wang
Ao Zhang
Ao Zhang
Jiang Wu
Jiang Wu
Wei Zhao
Wei Zhao
Wei Zhao
author_sort Xinran Song
collection DOAJ
description BackgroundInactivated 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.MethodsA 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]-γ/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.ResultsThe 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-γ 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.ConclusionsDelayed 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.
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spelling doaj-art-8c24e46ca5dc424db6cf209dcc3a514a2025-08-20T03:13:18ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-07-011610.3389/fimmu.2025.16366291636629Immune memory reactivation and T cell dynamics following 12-month homologous CoronaVac booster: a longitudinal cohort studyXinran Song0Xinran Song1Weixin Chen2Weixin Chen3Shuang Bai4Shuang Bai5Min Lv6Min Lv7Jian Wang8Jian Wang9Ao Zhang10Ao Zhang11Jiang Wu12Jiang Wu13Wei Zhao14Wei Zhao15Wei Zhao16Beijing Key Laboratory of Surveillance, Early Warning and Pathogen Research on Emerging Infectious Diseases, Beijing Center for Disease Prevention and Control, Beijing, ChinaBeijing Research Center for Respiratory Infectious Diseases, Beijing, ChinaBeijing Key Laboratory of Surveillance, Early Warning and Pathogen Research on Emerging Infectious Diseases, Beijing Center for Disease Prevention and Control, Beijing, ChinaBeijing Research Center for Respiratory Infectious Diseases, Beijing, ChinaBeijing Key Laboratory of Surveillance, Early Warning and Pathogen Research on Emerging Infectious Diseases, Beijing Center for Disease Prevention and Control, Beijing, ChinaBeijing Research Center for Respiratory Infectious Diseases, Beijing, ChinaBeijing Key Laboratory of Surveillance, Early Warning and Pathogen Research on Emerging Infectious Diseases, Beijing Center for Disease Prevention and Control, Beijing, ChinaBeijing Research Center for Respiratory Infectious Diseases, Beijing, ChinaBeijing Key Laboratory of Surveillance, Early Warning and Pathogen Research on Emerging Infectious Diseases, Beijing Center for Disease Prevention and Control, Beijing, ChinaBeijing Research Center for Respiratory Infectious Diseases, Beijing, ChinaBeijing Key Laboratory of Surveillance, Early Warning and Pathogen Research on Emerging Infectious Diseases, Beijing Center for Disease Prevention and Control, Beijing, ChinaBeijing Research Center for Respiratory Infectious Diseases, Beijing, ChinaBeijing Key Laboratory of Surveillance, Early Warning and Pathogen Research on Emerging Infectious Diseases, Beijing Center for Disease Prevention and Control, Beijing, ChinaBeijing Research Center for Respiratory Infectious Diseases, Beijing, ChinaBeijing Key Laboratory of Surveillance, Early Warning and Pathogen Research on Emerging Infectious Diseases, Beijing Center for Disease Prevention and Control, Beijing, ChinaBeijing Research Center for Respiratory Infectious Diseases, Beijing, ChinaSchool of Public Health, Capital Medical University, Beijing, ChinaBackgroundInactivated 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.MethodsA 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]-γ/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.ResultsThe 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-γ 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.ConclusionsDelayed 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.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1636629/fullSARS-CoV-2 inactivated vaccinehomologous boostingneutralizing antibodiesT cell exhaustionTh1 polarization
spellingShingle Xinran Song
Xinran Song
Weixin Chen
Weixin Chen
Shuang Bai
Shuang Bai
Min Lv
Min Lv
Jian Wang
Jian Wang
Ao Zhang
Ao Zhang
Jiang Wu
Jiang Wu
Wei Zhao
Wei Zhao
Wei Zhao
Immune memory reactivation and T cell dynamics following 12-month homologous CoronaVac booster: a longitudinal cohort study
Frontiers in Immunology
SARS-CoV-2 inactivated vaccine
homologous boosting
neutralizing antibodies
T cell exhaustion
Th1 polarization
title Immune memory reactivation and T cell dynamics following 12-month homologous CoronaVac booster: a longitudinal cohort study
title_full Immune memory reactivation and T cell dynamics following 12-month homologous CoronaVac booster: a longitudinal cohort study
title_fullStr Immune memory reactivation and T cell dynamics following 12-month homologous CoronaVac booster: a longitudinal cohort study
title_full_unstemmed Immune memory reactivation and T cell dynamics following 12-month homologous CoronaVac booster: a longitudinal cohort study
title_short Immune memory reactivation and T cell dynamics following 12-month homologous CoronaVac booster: a longitudinal cohort study
title_sort immune memory reactivation and t cell dynamics following 12 month homologous coronavac booster a longitudinal cohort study
topic SARS-CoV-2 inactivated vaccine
homologous boosting
neutralizing antibodies
T cell exhaustion
Th1 polarization
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1636629/full
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