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mRNA-1273 新型冠状病毒疫苗在近期异基因造血细胞移植受者中的应用:细胞和体液免疫应答的动态变化及加强效应。

mRNA-1273 SARS-CoV-2 vaccine in recently transplanted allogeneic hematopoietic cell transplant recipients: Dynamics of cellular and humoral immune responses and booster effect.

机构信息

Hematology Department, Hospital de la Santa Creu i Sant Pau, Carrer del Mas Casanovas 90, 08041 Barcelona, Spain; Josep Carreras Leukaemia Research Institute, Carrer de Sant Quintí 77-79, 08041 Barcelona, Spain; Institut d'Investigació Biomèdica (IIB) Sant Pau, Carrer de Sant Quintí 77-79, 08041 Barcelona, Spain; Autonomous University of Barcelona, Carrer de Sant Antoni Maria Claret 167, 08025 Barcelona, Spain; Catalan Institute of Oncology (ICO), Hospital Universitari Doctor Josep Trueta, 17007 Girona, Spain.

Institut d'Investigació Biomèdica (IIB) Sant Pau, Carrer de Sant Quintí 77-79, 08041 Barcelona, Spain; Autonomous University of Barcelona, Carrer de Sant Antoni Maria Claret 167, 08025 Barcelona, Spain; Immunology Department, Hospital de la Santa Creu i Sant Pau, Carrer del Mas Casanovas 90, 08041 Barcelona, Spain.

出版信息

Leuk Res. 2023 Sep;132:107347. doi: 10.1016/j.leukres.2023.107347. Epub 2023 Jun 22.

Abstract

Allogeneic hematopoietic stem cell transplant (HCT) recipients are at high risk of severe COVID-19 despite vaccination. Little is known about cellular response to SARS-CoV-2 vaccine in this population, especially in recently transplanted patients (RTP). In this single-center study we examined cellular and humoral response to the mRNA-1273 (Spikevax®) vaccine in recently transplanted patients (RTP, n = 49), and compared them to long-term transplanted patients (LTTP, n = 19) and healthy controls (n = 20) at three different timepoints: one and three months after the second dose (T1 and T2, respectively, 28 days apart), and one month after the third dose (T3). Controls did not receive a third dose. RTPs showed lower IgG anti-S1 titers than healthy controls at both T1 (mean 0.50 vs 0.94 arbitrary units -AU-, p < 0.0001) and T2 (0.37 vs 0.79 AU, p < 0.0001). They also presented lower titers than LTTPs at T1 (0.50 vs 0.66, p = 0.01), but no differences at T2 (0.37 vs 0.40 AU, p = 0.55). The rate of positive T-cell responses was lower in RTPs than in controls at both T1 and T2 (61.2 % vs 95 %, p = 0.007; 59.2 % vs 100 %, p = 0.001, respectively), but without statistically significant differences between transplanted groups. At T3 no differences were seen between RTPs and LTTPs as well, neither in IgG antibodies (p = 0.82) nor in cellular responses (p = 0.15), although a third dose increased the rate of positive cellular and humoral responses in approximately 50 % of recently transplanted patients. However, active immunosuppressive treatment severely diminished their chances to produce an adequate response.

摘要

异基因造血干细胞移植 (HCT) 受者尽管已接种疫苗,但仍有发生严重 COVID-19 的高风险。人们对该人群对 SARS-CoV-2 疫苗的细胞反应知之甚少,尤其是在最近接受移植的患者 (RTP) 中。在这项单中心研究中,我们检测了 mRNA-1273(Spikevax®)疫苗在最近接受移植的患者(RTP,n=49)中的细胞和体液反应,并将其与长期接受移植的患者(LTTP,n=19)和健康对照(n=20)在三个不同时间点进行比较:第二次剂量后一个月和三个月(分别为 T1 和 T2,间隔 28 天),以及第三次剂量后一个月(T3)。对照组未接种第三剂。在 T1(平均 0.50 与 0.94 个任意单位-AU-,p<0.0001)和 T2(0.37 与 0.79 AU,p<0.0001)时,RTP 的 IgG 抗 S1 滴度均低于健康对照组。他们在 T1 时的滴度也低于 LTTP(0.50 与 0.66,p=0.01),但在 T2 时无差异(0.37 与 0.40 AU,p=0.55)。在 T1 和 T2 时,RTP 的 T 细胞阳性反应率均低于对照组(61.2%与 95%,p=0.007;59.2%与 100%,p=0.001),但移植组之间无统计学差异。在 T3 时,RTP 与 LTTP 之间也没有差异,无论是 IgG 抗体(p=0.82)还是细胞反应(p=0.15),尽管第三剂使大约 50%的最近接受移植的患者的细胞和体液阳性反应率增加。然而,积极的免疫抑制治疗严重降低了他们产生足够反应的机会。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c90d/10284722/ebcab4121ecb/ga1_lrg.jpg

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