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在接受加强疫苗接种后,人类免疫缺陷病毒感染者体内可诱导出针对严重急性呼吸综合征冠状病毒2的特异性T细胞反应。

Severe acute respiratory syndrome coronavirus 2-specific T-cell responses are induced in people living with human immunodeficiency virus after booster vaccination.

作者信息

Wang Xiuwen, Li Yongzheng, Jin Junyan, Chai Xiaoran, Ma Zhenglai, Duan Junyi, Zhang Guanghui, Huang Tao, Zhang Xin, Zhang Tong, Wu Hao, Cao Yunlong, Su Bin

机构信息

Beijing Key Laboratory for HIV/AIDS Research, Sino-French Joint Laboratory for HIV/AIDS Research, Clinical and Research Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing 100069, China.

Biomedical Pioneering Innovation Center (BIOPIC), Peking University, Beijing 100069, China.

出版信息

Chin Med J (Engl). 2024 Nov 20;137(22):2734-2744. doi: 10.1097/CM9.0000000000003176. Epub 2024 Jul 18.

Abstract

BACKGROUND

T-cell-mediated immunity is crucial for the effective clearance of viral infection, but the T-cell-mediated immune responses that are induced by booster doses of inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in people living with human immunodeficiency virus (PLWH) remain unclear.

METHODS

Forty-five PLWH who had received antiretroviral therapy (ART) for more than two years and 29 healthy controls (HCs) at Beijing Youan Hospital were enrolled to assess the dynamic changes in T-cell responses between the day before the third vaccine dose (week 0) and 4 or 12 weeks (week 4 or week 12) after receiving the third dose of inactivated SARS-CoV-2 vaccine. Flow cytometry, enzyme-linked immunospot (ELISpot), and multiplex cytokines profiling were used to assess T-cell responses at the three timepoints in this study.

RESULTS

The results of the ELISpot and activation-induced marker (AIM) assays showed that SARS-CoV-2-specific T-cell responses were increased in both PLWH and HCs after the third dose of the inactivated SARS-CoV-2 vaccine, and a similar magnitude of immune response was induced against the Omicron (B.1.1.529) variant compared to the wild-type strain. In detail, spike-specific T-cell responses (measured by the ELISpot assay for interferon γ [IFN-γ] release) in both PLWH and HCs significantly increased in week 4, and the spike-specific T-cell responses in HCs were significantly stronger than those in PLWH 4 weeks after the third vaccination. In the AIM assay, spike-specific CD4 + T-cell responses peaked in both PLWH and HCs in week 12. Additionally, significantly higher spike-specific CD8 + T-cell responses were induced in PLWH than in HCs in week 12. In PLWH, the release of the cytokines interleukin-2 (IL-2), tumour necrosis factor-alpha (TNF-α), and IL-22 by peripheral blood mononuclear cells (PBMCs) that were stimulated with spike peptides increased in week 12. In addition, the levels of IL-4 and IL-5 were higher in PLWH than in HCs in week 12. Interestingly, the magnitude of SARS-CoV-2-specific T-cell responses in PLWH was negatively associated with the extent of CD8 + T-cell activation and exhaustion. In addition, positive correlations were observed between the magnitude of spike-specific T-cell responses (determined by measuring IFN-γ release by ELISpot) and the amounts of IL-4, IL-5, IL-2 and IL-17F.

CONCLUSIONS

Our findings suggested that SARS-CoV-2-specific T-cell responses could be enhanced by the booster dose of inactivated COVID-19 vaccines and further illustrate the importance of additional vaccination for PLWH.

摘要

背景

T细胞介导的免疫对于有效清除病毒感染至关重要,但人类免疫缺陷病毒感染者(PLWH)中,灭活严重急性呼吸综合征冠状病毒2(SARS-CoV-2)疫苗加强剂量所诱导的T细胞介导的免疫反应仍不清楚。

方法

招募了45名在北京佑安医院接受抗逆转录病毒治疗(ART)超过两年的PLWH和29名健康对照(HC),以评估在第三次疫苗接种前一天(第0周)和接种第三剂灭活SARS-CoV-2疫苗后4周或12周(第4周或第12周)之间T细胞反应的动态变化。本研究使用流式细胞术、酶联免疫斑点(ELISpot)和多重细胞因子分析来评估这三个时间点的T细胞反应。

结果

ELISpot和激活诱导标志物(AIM)检测结果显示,在接种第三剂灭活SARS-CoV-2疫苗后,PLWH和HC中的SARS-CoV-2特异性T细胞反应均增加,并且与野生型毒株相比,针对奥密克戎(B.1.1.529)变体诱导了相似程度的免疫反应。具体而言,PLWH和HC中的刺突特异性T细胞反应(通过检测干扰素γ [IFN-γ] 释放的ELISpot检测法测量)在第4周均显著增加,并且在第三次接种疫苗后4周,HC中的刺突特异性T细胞反应明显强于PLWH中的反应。在AIM检测中,PLWH和HC中的刺突特异性CD4+T细胞反应在第12周达到峰值。此外,在第12周,PLWH中诱导的刺突特异性CD8+T细胞反应显著高于HC。在PLWH中,用刺突肽刺激的外周血单个核细胞(PBMC)释放的细胞因子白细胞介素-2(IL-2)、肿瘤坏死因子-α(TNF-α)和IL-22在第12周增加。此外,在第12周,PLWH中的IL-4和IL-5水平高于HC。有趣的是,PLWH中SARS-CoV-2特异性T细胞反应的程度与CD8+T细胞活化和耗竭的程度呈负相关。此外,观察到刺突特异性T细胞反应的程度(通过ELISpot测量IFN-γ释放来确定)与IL-4、IL-5、IL-2和IL-17F的量之间存在正相关。

结论

我们的研究结果表明,灭活COVID-19疫苗的加强剂量可以增强SARS-CoV-2特异性T细胞反应,并进一步说明了PLWH额外接种疫苗的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7e0/11611240/5a3382d1f070/cm9-137-2734-g001.jpg

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