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实体器官移植受者接种ChAdOx1 nCoV-19疫苗后针对严重急性呼吸综合征冠状病毒2(SARS-CoV-2)的抗体、B细胞和T细胞免疫反应

SARS-CoV-2-Specific Antibodies, B Cell and T Cell Immune Responses after ChAdOx1 nCoV-19 Vaccination in Solid Organ Transplant Recipients.

作者信息

Phornkittikorn Pattaraphorn, Kantachuvesiri Surasak, Sobhonslidsuk Abhasnee, Yingchoncharoen Teerapat, Kiertiburanakul Sasisopin, Bruminhent Jackrapong

机构信息

Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand.

Ramathibodi Excellence Center for Organ Transplantation, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand.

出版信息

Vaccines (Basel). 2024 May 15;12(5):541. doi: 10.3390/vaccines12050541.

DOI:10.3390/vaccines12050541
PMID:38793792
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11125913/
Abstract

BACKGROUND

Immunization against SARS-CoV-2 is essential for vulnerable solid organ transplant (SOT) recipients who are at risk of infection. However, there are concerns about suboptimal immunogenicity, especially in humoral immunity (HMI), and limited exploration of cell-mediated immune (CMI) responses. The primary objective of this study was to assess the immunogenicity of ChAdOx1 nCoV-19 vaccination in SOT recipients. The secondary endpoint was to evaluate factors that affect immunogenicity and adverse events (AEs) following immunization in SOT recipients.

METHODS

All adult SOT recipients who received the two-dose ChAdOx1 nCoV-19 vaccine at a 12-week interval underwent measurements of HMI by evaluating anti-receptor-binding domain (RBD) IgG levels and CMI by investigating SARS-CoV-2-specific T cell and B cell responses before and after complete vaccination, around 2-4 weeks post-vaccination, and compared to controls. AEs were monitored in all participants.

RESULTS

The study included 63 SOT recipients: 44 kidney recipients, 16 liver recipients, and 3 heart transplant recipients, along with 11 immunocompetent controls. Among SOT recipients, 36% were female, and the median (IQR) age was 52 (42-61). The median (IQR) time since transplant was 55 (28-123) months. After the second dose, the median (IQR) anti-RBD antibody levels were significantly lower in SOT recipients compared to those in the control group (8.3 [0.4-46.0] vs. 272.2 [178.1-551.6] BAU/mL, < 0.01). This resulted in a seroconversion rate (anti-RBD antibody > 7.1 BAU/mL) of 51% among SOT recipients and 100% among controls ( = 0.008). Receiving the vaccine beyond one year post-transplant significantly affected seroconversion (OR 9.04, 95% CI 1.04-78.56, = 0.046), and low-dose mycophenolic acid marginally affected seroconversion (OR 2.67, 95% CI 0.89-7.96, = 0.079). RBD-specific B cell responses were also significantly lower compared to those in the control group (0 [0-4] vs. 10 [6-22] SFUs/10 PBMCs, = 0.001). Similarly, S1- and SNMO-specific T cell responses were significantly lower compared to those in the control group (48 [16-128] vs. 216 [132-356] SFUs/10 PBMCs, = 0.004 and 20 [4-48] vs. 92 [72-320] SFUs/10 PBMCs, = 0.004). AEs were generally mild and spontaneously resolved.

CONCLUSIONS

SOT recipients who received the full two-dose ChAdOx1 nCoV-19 vaccine demonstrated significantly diminished HMI and CMI responses compared to immunocompetent individuals. Consideration should be given to administering additional vaccine doses or optimizing immunosuppressant regimens during vaccination (Thai Clinical Trial Registry: TCTR20210523002).

摘要

背景

对于有感染风险的实体器官移植(SOT)受者,接种新型冠状病毒2(SARS-CoV-2)疫苗至关重要。然而,人们担心免疫原性欠佳,尤其是体液免疫(HMI)方面,并且对细胞介导免疫(CMI)反应的探索有限。本研究的主要目的是评估ChAdOx1 nCoV-19疫苗在SOT受者中的免疫原性。次要终点是评估影响SOT受者免疫接种后免疫原性和不良事件(AE)的因素。

方法

所有间隔12周接受两剂ChAdOx1 nCoV-19疫苗的成年SOT受者,在全程接种前、接种后约2-4周以及接种后完成全程接种后,通过评估抗受体结合域(RBD)IgG水平来测量HMI,并通过研究SARS-CoV-2特异性T细胞和B细胞反应来测量CMI,并与对照组进行比较。对所有参与者监测AE。

结果

该研究纳入了63名SOT受者:44名肾移植受者、16名肝移植受者和3名心脏移植受者,以及11名免疫功能正常的对照者。在SOT受者中,36%为女性,年龄中位数(四分位间距)为52岁(42-61岁)。移植后的中位(四分位间距)时间为55个月(28-123个月)。与对照组相比,SOT受者在第二剂疫苗接种后,抗RBD抗体水平中位数(四分位间距)显著较低(8.3[0.4-46.0] vs. 272.2[178.1-551.6] BAU/mL,P<0.01)。这导致SOT受者的血清转化率(抗RBD抗体>7.1 BAU/mL)为51%,对照组为100%(P=0.008)。移植后超过一年接种疫苗显著影响血清转化(比值比9.04,95%置信区间1.04-78.56,P=0.046),低剂量霉酚酸对血清转化有轻微影响(比值比2.67,95%置信区间0.89-7.96,P=0.079)。与对照组相比,RBD特异性B细胞反应也显著较低(0[0-4] vs. 10[6-22] SFUs/10个外周血单核细胞,P=0.001)。同样,与对照组相比,S1和SNMO特异性T细胞反应显著较低(48[16-128] vs. 216[132-356] SFUs/10个外周血单核细胞,P=0.004和20[4-48] vs. 92[72-320] SFUs/10个外周血单核细胞,P=0.004)。AE一般较轻且可自行缓解。

结论

与免疫功能正常的个体相比

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8eab/11125913/d66ea91eca49/vaccines-12-00541-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8eab/11125913/1fe91dd42528/vaccines-12-00541-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8eab/11125913/8a008d0dd587/vaccines-12-00541-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8eab/11125913/fb387128c586/vaccines-12-00541-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8eab/11125913/7767ad69dc32/vaccines-12-00541-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8eab/11125913/d66ea91eca49/vaccines-12-00541-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8eab/11125913/1fe91dd42528/vaccines-12-00541-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8eab/11125913/8a008d0dd587/vaccines-12-00541-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8eab/11125913/fb387128c586/vaccines-12-00541-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8eab/11125913/7767ad69dc32/vaccines-12-00541-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8eab/11125913/d66ea91eca49/vaccines-12-00541-g005.jpg

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Vaccines (Basel). 2022 Oct 10;10(10):1690. doi: 10.3390/vaccines10101690.
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Benefits of Inactivated Vaccine and Viral Vector Vaccine Immunization on COVID-19 Infection in Kidney Transplant Recipients.灭活疫苗和病毒载体疫苗免疫对肾移植受者新型冠状病毒肺炎感染的益处
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