在感染 HIV 的个体中，三剂 SARS-CoV-2 灭活疫苗后持久的自然杀伤细胞反应。
Durable natural killer cell response after three doses of SARS-CoV-2 inactivated vaccine in HIV-infected individuals.
机构信息
Beijing Key Laboratory for HIV/AIDS Research, Sino-French Joint Laboratory for Research on Humoral Immune Response to HIV Infection, Clinical and Research Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing 100069, China.
National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China.
出版信息
Chin Med J (Engl). 2023 Dec 20;136(24):2948-2959. doi: 10.1097/CM9.0000000000002947. Epub 2023 Nov 27.
BACKGROUND
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine can induce a potent cellular and humoral immune response to protect against SARS-CoV-2 infection. However, it was unknown whether SARS-CoV-2 vaccination can induce effective natural killer (NK) cell response in people living with human immunodeficiency virus (PLWH) and healthy individuals.
METHODS
Forty-seven PLWH and thirty healthy controls (HCs) inoculated with SARS-CoV-2 inactivated vaccine were enrolled from Beijing Youan Hospital in this study. The effect of SARS-CoV-2 vaccine on NK cell frequency, phenotype, and function in PLWH and HCs was evaluated by flow cytometry, and the response of NK cells to SARS-CoV-2 Omicron Spike (SARS-2-OS) protein stimulation was also evaluated.
RESULTS
SARS-CoV-2 vaccine inoculation elicited activation and degranulation of NK cells in PLWH, which peaked at 2 weeks and then decreased to a minimum at 12 weeks after the third dose of vaccine. However, in vitro stimulation of the corresponding peripheral blood monocular cells from PLWH with SARS-2-OS protein did not upregulate the expression of the aforementioned markers. Additionally, the frequencies of NK cells expressing the activation markers CD25 and CD69 in PLWH were significantly lower than those in HCs at 0, 4 and 12 weeks, but the percentage of CD16 + NK cells in PLWH was significantly higher than that in HCs at 2, 4 and 12 weeks after the third dose of vaccine. Interestingly, the frequency of CD16 + NK cells was significantly negatively correlated with the proportion of CD107a + NK cells in PLWH at each time point after the third dose. Similarly, this phenomenon was also observed in HCs at 0, 2, and 4 weeks after the third dose. Finally, regardless of whether NK cells were stimulated with SARS-2-OS or not, we did not observe any differences in the expression of NK cell degranulation markers between PLWH and HCs.
CONCLUSION
s:SARS-CoV-2 vaccine elicited activation and degranulation of NK cells, indicating that the inoculation of SARS-CoV-2 vaccine enhances NK cell immune response.
背景
严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）疫苗可诱导强烈的细胞和体液免疫应答，以预防 SARS-CoV-2 感染。然而，尚不清楚 SARS-CoV-2 疫苗接种是否能在人类免疫缺陷病毒（PLWH）感染者和健康个体中诱导有效的自然杀伤（NK）细胞应答。
方法
本研究纳入了来自北京佑安医院的 47 名 PLWH 和 30 名健康对照（HC），他们均接种了 SARS-CoV-2 灭活疫苗。通过流式细胞术评估 SARS-CoV-2 疫苗对 PLWH 和 HCs 中 NK 细胞频率、表型和功能的影响，并评估 NK 细胞对 SARS-CoV-2 奥密克戎刺突（SARS-2-OS）蛋白刺激的反应。
结果
SARS-CoV-2 疫苗接种可诱导 PLWH 中 NK 细胞的活化和脱颗粒，其在第三剂疫苗接种后 2 周达到峰值，然后在 12 周时降至最低。然而，用 SARS-2-OS 蛋白体外刺激 PLWH 的相应外周血单核细胞并未上调上述标志物的表达。此外，PLWH 中表达活化标志物 CD25 和 CD69 的 NK 细胞频率在 0、4 和 12 周时明显低于 HCs，但在第三剂疫苗接种后 2、4 和 12 周时，PLWH 中 CD16+NK 细胞的百分比明显高于 HCs。有趣的是，在第三剂疫苗接种后每个时间点，PLWH 中 CD16+NK 细胞的频率与 CD107a+NK 细胞的比例呈显著负相关。同样的现象也发生在第三剂疫苗接种后 0、2 和 4 周的 HCs 中。最后，无论 NK 细胞是否被 SARS-2-OS 刺激，我们都没有观察到 PLWH 和 HCs 之间 NK 细胞脱颗粒标志物表达的差异。
结论
SARS-CoV-2 疫苗诱导了 NK 细胞的活化和脱颗粒，表明接种 SARS-CoV-2 疫苗增强了 NK 细胞免疫应答。
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