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严重急性呼吸综合征冠状病毒2感染及疫苗接种对急性淋巴细胞白血病患儿影响的临床研究

A Clinical Investigation Into the Effects of Severe Acute Respiratory Syndrome Coronavirus 2 Infection and Vaccination in Children With Acute Lymphoblastic Leukemia.

作者信息

Wu Zhengcun, Jiang Hongchao, Zhou Yanan, Yang Yun, Jiang Haiyan, Zhang Fang, Zhe Linyang, Tang Ruixia, Xu Jianyu, Yan Lingmei, Lu Shuaiyao, Zhang Tiesong, Sun Qiangming

机构信息

National Kunming High-Level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China.

Institute of Pediatrics, The Kunming Children's Hospital, Kunming, China.

出版信息

J Med Virol. 2025 Aug;97(8):e70492. doi: 10.1002/jmv.70492.

DOI:10.1002/jmv.70492
PMID:40788085
Abstract

This study systematically evaluated the humoral immune responses and cytokine profiles of 259 pediatric participants, comprising both healthy individuals and patients with Acute Lymphoblastic Leukemia (ALL), following either administration of an inactivated SARS-CoV-2 vaccine or natural infection. The data indicate that vaccination elicits measurable immune responses in both groups, supporting its relevance in immunocompromised pediatric populations. Although antigen-specific responses to the spike (S) protein and receptor-binding domain (RBD) were attenuated in the ALL cohort, levels of neutralizing antibodies and antibodies capable of inhibiting RBD-ACE2 binding were comparable to those in healthy controls, suggesting that functional antibody-mediated immunity can still be achieved in ALL patients. Notably, vaccinated ALL patients exhibited higher neutralizing antibody titers against the SARS-CoV-2 prototype strain and major variants of concern (Alpha, Beta, Delta) than their healthy counterparts. However, both groups demonstrated markedly reduced responses to the Omicron variant, underscoring its substantial immune escape potential. Cytokine analysis revealed dysregulated expression patterns in the ALL group, with minimal modulation following vaccination, in contrast to the immunosuppressive cytokine regulation observed in healthy individuals. Importantly, the JAK/STAT signaling pathway emerged as a key component in the immune response to SARS-CoV-2 among healthy subjects. These insights provide a scientific basis for the optimization of COVID-19 immunization strategies tailored to vulnerable pediatric groups.

摘要

本研究系统评估了259名儿科参与者的体液免疫反应和细胞因子谱,这些参与者包括健康个体和急性淋巴细胞白血病(ALL)患者,他们在接种灭活SARS-CoV-2疫苗或自然感染后接受了评估。数据表明,疫苗接种在两组中均引发了可测量的免疫反应,支持了其在免疫功能低下的儿科人群中的相关性。尽管ALL队列中对刺突(S)蛋白和受体结合域(RBD)的抗原特异性反应减弱,但中和抗体水平以及能够抑制RBD-ACE2结合的抗体水平与健康对照组相当,这表明ALL患者仍可实现功能性抗体介导的免疫。值得注意的是,接种疫苗的ALL患者针对SARS-CoV-2原型株和主要关注变体(Alpha、Beta、Delta)的中和抗体滴度高于健康对照。然而,两组对奥密克戎变体的反应均明显降低,这突出了其巨大的免疫逃逸潜力。细胞因子分析显示ALL组的表达模式失调,接种疫苗后调节作用最小,这与健康个体中观察到的免疫抑制性细胞因子调节形成对比。重要的是,JAK/STAT信号通路成为健康受试者对SARS-CoV-2免疫反应的关键组成部分。这些见解为优化针对脆弱儿科群体的COVID-19免疫策略提供了科学依据。

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