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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Frontiers Media S.A.
2025-07-01
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| 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. |
| format | Article |
| id | doaj-art-8c24e46ca5dc424db6cf209dcc3a514a |
| institution | DOAJ |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| 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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