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在接受免疫检查点抑制剂治疗的癌症患者中重复接种 SARS-CoV-2 疫苗:诱导高亲和力抗 RBD 中和抗体。

Repeated SARS-CoV-2 vaccination in cancer patients treated with immune checkpoint inhibitors: induction of high-avidity anti-RBD neutralizing antibodies.

机构信息

Clinical Immunology and Allergy Unit, Department of Clinical and Experimental Medicine, University of Pisa, Via Roma, 67, 56126, Pisa, Italy.

Oncology Unit, Azienda Ospedaliera Universitaria Pisana, Pisa, Italy.

出版信息

Int J Clin Oncol. 2023 Mar;28(3):363-369. doi: 10.1007/s10147-023-02295-0. Epub 2023 Jan 23.

Abstract

BACKGROUND

Cancer patients are more vulnerable to COVID-19 and are thus given high priority in vaccination campaigns. In solid cancer patients treated with checkpoint inhibitors, we evaluated the amount of anti-RBD and neutralizing antibodies and antibody avidity after two or three doses of the vaccine.

METHODS

Thirty-eight solid cancer patients, 15 untreated hematological patients and 21 healthy subjects were enrolled in the study. Blood was collected before the first dose (T0), 21 days after the second (T2) and in 18 solid cancer patients also 15 days after the third dose of vaccine (T3). IgG, IgM and IgA anti-RBD antibodies were detected by ELISA. Neutralizing antibodies were measured testing the inhibition of RBD binding to ACE2. Antibody avidity was evaluated in 18 patients by a urea avidity ELISA.

RESULTS

IgG anti-RBD antibodies were produced in 65.8% of the cancer patients at T2, and in 60% of hematological patients at levels lower than healthy controls. IgM and IgA anti-RBD antibodies were also produced in 5.3% and 21% cancer patients, respectively. At T3, a significant increase in anti-RBD IgG levels was observed. Neutralizing antibodies were produced in 68.4% of cancer patients as compared with 93% of untreated hematological patients and 100% of controls, at titers lower than in healthy subjects. At T3, neutralizing antibodies and avidity of IgG anti-RBD increased; 6/18 patients negative at T2 developed neutralizing antibodies at T3.

CONCLUSION

The data indicate that in cancer patients mRNA vaccine induces high avidity anti-RBD antibodies and neutralizing antibodies that increase after the third dose. The process of induction and selection of high-affinity antibodies is apparently unaffected by the treatment with anti-PD-1 or anti-PD-L1 antibodies.

摘要

背景

癌症患者更容易感染 COVID-19,因此在疫苗接种活动中被给予高度优先考虑。在接受检查点抑制剂治疗的实体瘤患者中,我们评估了两到三剂疫苗接种后抗 RBD 和中和抗体的数量和抗体亲合力。

方法

研究纳入了 38 名实体瘤患者、15 名未经治疗的血液病患者和 21 名健康受试者。在第一次剂量(T0)前、第二次剂量后 21 天(T2)以及 18 名实体瘤患者的第三次剂量后 15 天(T3)采集血液。通过 ELISA 检测 IgG、IgM 和 IgA 抗 RBD 抗体。通过检测 RBD 与 ACE2 结合的抑制作用来测量中和抗体。在 18 名患者中通过脲素亲合力 ELISA 评估抗体亲合力。

结果

在 T2 时,65.8%的癌症患者产生了 IgG 抗 RBD 抗体,而 60%的血液病患者的抗体水平低于健康对照组。5.3%和 21%的癌症患者也产生了 IgM 和 IgA 抗 RBD 抗体。在 T3 时,观察到抗 RBD IgG 水平显著增加。与未接受治疗的血液病患者的 93%和对照组的 100%相比,68.4%的癌症患者产生了中和抗体,其滴度低于健康受试者。在 T3 时,中和抗体和 IgG 抗 RBD 的亲合力增加;在 T2 时为阴性的 6/18 名患者在 T3 时产生了中和抗体。

结论

数据表明,在癌症患者中,mRNA 疫苗诱导高亲合力的抗 RBD 抗体,并且在第三次剂量后增加。抗 PD-1 或抗 PD-L1 抗体治疗显然不会影响高亲和力抗体的诱导和选择过程。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1962/9988729/fe4223df784b/10147_2023_2295_Fig1_HTML.jpg

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