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接受贝那鲁肽、度普利尤单抗或美泊利珠单抗治疗的患者接种 SARS-CoV-2 疫苗后的免疫应答较低。

Patients taking benralizumab, dupilumab, or mepolizumab have lower postvaccination SARS-CoV-2 immunity.

机构信息

Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, Ga; Department of Medicine, Atlanta Veterans Affairs Healthcare System, Atlanta, Ga.

Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, Ga.

出版信息

J Allergy Clin Immunol. 2024 Aug;154(2):435-446. doi: 10.1016/j.jaci.2024.03.029. Epub 2024 Jun 13.

Abstract

BACKGROUND

Biologic therapies inhibiting the IL-4 or IL-5 pathways are very effective in the treatment of asthma and other related conditions. However, the cytokines IL-4 and IL-5 also play a role in the generation of adaptive immune responses. Although these biologics do not cause overt immunosuppression, their effect in primary severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunization has not been studied completely.

OBJECTIVE

Our aim was to evaluate the antibody and cellular immunity after SARS-CoV-2 mRNA vaccination in patients on biologics (PoBs).

METHODS

Patients with severe asthma or atopic dermatitis who were taking benralizumab, dupilumab, or mepolizumab and had received the initial dose of the 2-dose adult SARS-CoV-2 mRNA vaccine were enrolled in a prospective, observational study. As our control group, we used a cohort of immunologically healthy subjects (with no significant immunosuppression) who were not taking biologics (NBs). We used a multiplexed immunoassay to measure antibody levels, neutralization assays to assess antibody function, and flow cytometry to quantitate Spike-specific lymphocytes.

RESULTS

We analyzed blood from 57 patients in the PoB group and 46 control subjects from the NB group. The patients in the PoB group had lower levels of SARS-CoV-2 antibodies, pseudovirus neutralization, live virus neutralization, and frequencies of Spike-specific B and CD8 T cells at 6 months after vaccination. In subgroup analyses, patients with asthma who were taking biologics had significantly lower pseudovirus neutralization than did subjects with asthma who were not taking biologics.

CONCLUSION

The patients in the PoB group had reduced SARS-CoV-2-specific antibody titers, neutralizing activity, and virus-specific B- and CD8 T-cell counts. These results have implications when considering development of a more individualized immunization strategy in patients who receive biologic medications blocking IL-4 or IL-5 pathways.

摘要

背景

抑制白细胞介素 4 或白细胞介素 5 通路的生物疗法在治疗哮喘和其他相关疾病方面非常有效。然而,细胞因子白细胞介素 4 和白细胞介素 5 也在适应性免疫反应的产生中发挥作用。尽管这些生物制剂不会引起明显的免疫抑制,但它们在原发性严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)免疫接种中的作用尚未完全研究。

目的

我们旨在评估接受生物制剂(PoB)治疗的患者在接受 SARS-CoV-2 mRNA 疫苗接种后的抗体和细胞免疫。

方法

纳入正在接受贝那鲁肽、度普利尤单抗或美泊利珠单抗治疗且已接受 2 剂成人 SARS-CoV-2 mRNA 疫苗初始剂量的重度哮喘或特应性皮炎患者进行前瞻性观察性研究。我们使用一组未接受生物制剂(NB)治疗的免疫健康对照者(无明显免疫抑制)作为对照组。我们使用多重免疫分析法测量抗体水平,中和测定评估抗体功能,以及流式细胞术定量 Spike 特异性淋巴细胞。

结果

我们分析了 PoB 组 57 例患者和 NB 组 46 例对照者的血液样本。接种疫苗 6 个月后,PoB 组患者的 SARS-CoV-2 抗体、假病毒中和、活病毒中和以及 Spike 特异性 B 和 CD8 T 细胞频率均较低。亚组分析显示,接受生物制剂治疗的哮喘患者的假病毒中和率明显低于未接受生物制剂治疗的哮喘患者。

结论

PoB 组患者的 SARS-CoV-2 特异性抗体滴度、中和活性以及病毒特异性 B 和 CD8 T 细胞计数降低。这些结果在考虑为接受白细胞介素 4 或白细胞介素 5 通路阻断生物制剂治疗的患者制定更个体化的免疫接种策略时具有重要意义。

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