Role of senescent CD4+ T cells in breakthrough infection of the new variant strain of SARS-CoV-2 in elderly patients
Abstract Background In late 2022, Beijing, China saw a large-scale BF.7 Omicron variant breakthrough infection. However, the impact of COVID-19 vaccines on elderly breakthrough-infected patients’ antibodies and immune cells response was unclear. Methods We recruited 329 inpatients over 65 with BF.7...
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| Format: | Article |
| Language: | English |
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BMC
2025-07-01
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| Series: | Journal of Translational Medicine |
| Online Access: | https://doi.org/10.1186/s12967-025-06756-0 |
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| author | Zhaoyuan Liang Hua Zhang Lu Xu Nan Li Zhongnan Yin Yongchang Sun Ning Shen Zhengyang Guo Yuqing Wang Lixiang Xue Jie Zhang Lin Zeng Jianling Yang Siyan Zhan |
| author_facet | Zhaoyuan Liang Hua Zhang Lu Xu Nan Li Zhongnan Yin Yongchang Sun Ning Shen Zhengyang Guo Yuqing Wang Lixiang Xue Jie Zhang Lin Zeng Jianling Yang Siyan Zhan |
| author_sort | Zhaoyuan Liang |
| collection | DOAJ |
| description | Abstract Background In late 2022, Beijing, China saw a large-scale BF.7 Omicron variant breakthrough infection. However, the impact of COVID-19 vaccines on elderly breakthrough-infected patients’ antibodies and immune cells response was unclear. Methods We recruited 329 inpatients over 65 with BF.7 breakthrough infections. We analyzed the link between vaccination and survival in 67 sampled patients, investigating changes in antibody levels, cytokine profiles, as well as immune phenotypes. Results Experiments revealed that while vaccination could raise antibody levels in the elderly, it showed no significant neutralizing activity against the emerging COVID-19 variant XBB. Flow cytometry showed vaccination increased the proportion of CD4+ senescent T cells. Moreover, we found that elevated frequencies of CD4+ Tsens cells were associated with reduced antigen-specific CD4+ T cell activation, diminished IL-2 production, and lower proportions of Tfh cells, which ultimately leading to impaired neutralizing antibody production, particularly against new emerging variants. Conclusions We found the immunological efficacy of inactivated vaccines in elderly patients is influenced by the proportion of CD4+ senescent T cells. Future elderly vaccination strategies need optimization in dose number and timing, and future vaccine design should aim to minimize the generation of CD4+ senescent T cells. |
| format | Article |
| id | doaj-art-c170a55b48f2417885f3473a0155f9ee |
| institution | Kabale University |
| issn | 1479-5876 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj-art-c170a55b48f2417885f3473a0155f9ee2025-08-20T04:01:40ZengBMCJournal of Translational Medicine1479-58762025-07-0123111310.1186/s12967-025-06756-0Role of senescent CD4+ T cells in breakthrough infection of the new variant strain of SARS-CoV-2 in elderly patientsZhaoyuan Liang0Hua Zhang1Lu Xu2Nan Li3Zhongnan Yin4Yongchang Sun5Ning Shen6Zhengyang Guo7Yuqing Wang8Lixiang Xue9Jie Zhang10Lin Zeng11Jianling Yang12Siyan Zhan13Center of Basic Medical Research, Institute of Medical Innovation and Research, Peking University Third HospitalResearch Center of Clinical Epidemiology, Institute of Medical Innovation and Research, Peking University Third HospitalResearch Center of Clinical Epidemiology, Institute of Medical Innovation and Research, Peking University Third HospitalResearch Center of Clinical Epidemiology, Institute of Medical Innovation and Research, Peking University Third HospitalBiobank, Institute of Medical Innovation and Research, Peking University Third HospitalDepartment of Respiratory and Critical Care Medicine, Peking University Third HospitalDepartment of Respiratory and Critical Care Medicine, Peking University Third HospitalCenter of Basic Medical Research, Institute of Medical Innovation and Research, Peking University Third HospitalCenter of Basic Medical Research, Institute of Medical Innovation and Research, Peking University Third HospitalCenter of Basic Medical Research, Institute of Medical Innovation and Research, Peking University Third HospitalCenter of Basic Medical Research, Institute of Medical Innovation and Research, Peking University Third HospitalResearch Center of Clinical Epidemiology, Institute of Medical Innovation and Research, Peking University Third HospitalCenter of Basic Medical Research, Institute of Medical Innovation and Research, Peking University Third HospitalResearch Center of Clinical Epidemiology, Institute of Medical Innovation and Research, Peking University Third HospitalAbstract Background In late 2022, Beijing, China saw a large-scale BF.7 Omicron variant breakthrough infection. However, the impact of COVID-19 vaccines on elderly breakthrough-infected patients’ antibodies and immune cells response was unclear. Methods We recruited 329 inpatients over 65 with BF.7 breakthrough infections. We analyzed the link between vaccination and survival in 67 sampled patients, investigating changes in antibody levels, cytokine profiles, as well as immune phenotypes. Results Experiments revealed that while vaccination could raise antibody levels in the elderly, it showed no significant neutralizing activity against the emerging COVID-19 variant XBB. Flow cytometry showed vaccination increased the proportion of CD4+ senescent T cells. Moreover, we found that elevated frequencies of CD4+ Tsens cells were associated with reduced antigen-specific CD4+ T cell activation, diminished IL-2 production, and lower proportions of Tfh cells, which ultimately leading to impaired neutralizing antibody production, particularly against new emerging variants. Conclusions We found the immunological efficacy of inactivated vaccines in elderly patients is influenced by the proportion of CD4+ senescent T cells. Future elderly vaccination strategies need optimization in dose number and timing, and future vaccine design should aim to minimize the generation of CD4+ senescent T cells.https://doi.org/10.1186/s12967-025-06756-0 |
| spellingShingle | Zhaoyuan Liang Hua Zhang Lu Xu Nan Li Zhongnan Yin Yongchang Sun Ning Shen Zhengyang Guo Yuqing Wang Lixiang Xue Jie Zhang Lin Zeng Jianling Yang Siyan Zhan Role of senescent CD4+ T cells in breakthrough infection of the new variant strain of SARS-CoV-2 in elderly patients Journal of Translational Medicine |
| title | Role of senescent CD4+ T cells in breakthrough infection of the new variant strain of SARS-CoV-2 in elderly patients |
| title_full | Role of senescent CD4+ T cells in breakthrough infection of the new variant strain of SARS-CoV-2 in elderly patients |
| title_fullStr | Role of senescent CD4+ T cells in breakthrough infection of the new variant strain of SARS-CoV-2 in elderly patients |
| title_full_unstemmed | Role of senescent CD4+ T cells in breakthrough infection of the new variant strain of SARS-CoV-2 in elderly patients |
| title_short | Role of senescent CD4+ T cells in breakthrough infection of the new variant strain of SARS-CoV-2 in elderly patients |
| title_sort | role of senescent cd4 t cells in breakthrough infection of the new variant strain of sars cov 2 in elderly patients |
| url | https://doi.org/10.1186/s12967-025-06756-0 |
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