Boosting of Waned Humoral and Cellular Responses to SARS-CoV-2 Variants of Concern Among Patients with Cancer.
Boosting of Waned Humoral and Cellular Responses to SARS-CoV-2 Variants of Concern Among Patients with Cancer.
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DOI：
10.1158/2767-9764.crc-22-0298
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发表时间：
2022-11-17
期刊：
影响因子：
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通讯作者：
Irshad S
中科院分区：
文献类型：
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作者：
McKenzie DR;Graham R;Lechmere T;Domingo-Vila C;Alaguthurai T;Arman C;Pollock E;Gousis C;Kakkassery H;Carpenter E;Kurshan A;Vidler J;Kulasekararaj A;Patten P;North BV;Tree T;Doores KJ;Hayday AC;Irshad S
这项研究提供了三种SARS-CoV-2疫苗接种对实体癌患者，血液恶性肿瘤患者和非癌症患者体液和细胞免疫的影响的纵向见解。对于所有队列，在第二次疫苗接种后长达9个月的时间内，病毒中和免疫力显著耗尽，一个显著的例外是SARS-CoV-2抗原特异性T细胞产生IL 2。免疫力在第三剂疫苗时恢复，但大量血液恶性肿瘤患者除外，对他们来说，癌症类型和治疗方案与无应答相关。因此，尽管大多数骨髓增生异常综合征患者的反应明显良好，但一些在接种后2周内接受癌症治疗的其他血液系统恶性肿瘤患者尽管接种了3次疫苗，仍未出现血清转化。此外，研究过程中的SARS-CoV-2暴露既不能防止免疫力减弱，即使在健康对照组中也不能保证疫苗的反应性。这些数据提供了真实世界的人类免疫学见解，可以为癌症患者的健康政策提供信息。全球卫生政策依赖于SARS-CoV-2疫苗的有效性，这是基于我们对连续接种疫苗所提供的保护的持久性和加强接种的有效性的理解，特别是在可能构成病毒储存库的免疫功能低下的患者人群中。在这里，我们有：（i）阐明癌症患者中抗体减弱的程度、针对亲本病毒和关注变体的血清中和滴度以及T细胞应答;（ii）评估癌症患者对第三剂COVID-19疫苗的免疫应答;以及（iii）提供癌症患者接种第三剂BNT 162 b2 COVID-19疫苗后的安全性数据。
This study offers longitudinal insight into the impact of three SARS-CoV-2 vaccinations on humoral and cellular immunity in patients with solid cancers, patients with hematologic malignancies, and persons without cancer. For all cohorts, virus-neutralizing immunity was significantly depleted over a period of up to 9 months following the second vaccine dose, the one striking exception being IL2 production by SARS-CoV-2 antigen-specific T cells. Immunity was restored by the third vaccine dose, except in a substantial number of patients with hematologic malignancy, for whom both cancer type and treatment schedule were associated with nonresponse. Thus, whereas most patients with myelodysplastic syndrome were conspicuously good responders, some patients with other hematologic malignancies receiving cancer therapies within 2 weeks of vaccination showed no seroconversion despite three vaccine doses. Moreover, SARS-CoV-2 exposure during the course of the study neither prevented immunity waning, even in healthy controls, nor guaranteed vaccine responsiveness. These data offer real-world human immunologic insights that can inform health policy for patients with cancer. Global health policy reliant on SARS-CoV-2 vaccine effectiveness is underpinned by our understanding of the durability of protection offered by sequential vaccinations and the efficacy of boosting, especially in immunocompromised patient populations who might constitute virus reservoirs. Here, we have: (i) clarified in patients with cancer the degree of waning of antibodies, serum neutralization titres against parental virus and variants of concern, and T-cell responses; (ii) evaluated the immune response among patients with cancer to a third dose of COVID-19 vaccine; and (iii) provided safety data following the third dose of the BNT162b2 COVID-19 vaccine in patients with cancer.