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接受一剂、两剂或三剂抗SARS-CoV-2腺病毒载体疫苗后肝移植和肠移植患者的血清转化。阿根廷的单中心经验。

Seroconversion in liver and intestine transplant patients after one, two or three doses of adenoviral vector vaccines against SARS-CoV-2. Single center experience in Argentina.

作者信息

Silvina Yantorno, Renata Curciarello, Gastón Rizzo, Compagnucci Malena Ferreyra, Lorena Tau, Laura Delaplace, Valeria Descalzi, Gabriel Gondolesi, Guillermo Docena, Martin Rumbo, Virginia Gentilini María

机构信息

Unidad de Hepatología, Cirugía Hepatobiliar Y Trasplante Hepático, Hospital Universitario Fundación Favaloro, Buenos Aires, Argentina.

Instituto de Estudios Inmunológicos y Fisiopatológicos (IIFP), CONICET, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, La Plata, Argentina.

出版信息

Hum Immunol. 2024 Nov;85(6):111091. doi: 10.1016/j.humimm.2024.111091. Epub 2024 Sep 11.

Abstract

BACKGROUND

The capacity of different anti-SARS-CoV-2 vaccines to elicit immune response is not equivalent in the healthy population compared to chronically immunosuppressed patients. Most of the reports available to assess the effects of anti-SARS-CoV-2 vaccines on solid organ transplant recipients (SOTR) were performed using mRNA-based vaccines.

OBJECTIVE

This study aims to assess the seroconversion rate in a cohort of liver and liver- intestinal transplant patients after vaccination with the non-replicative vector-based vaccines after transplantation used in our country, Argentina (rAd26-rAd5 (Sputnik V) and ChAdOx11 nCoV-19 (AZD1222) (Astra Zeneca-Oxford).

METHODS

One hundred and three (103) liver and liver-intestinal transplant recipients were enrolled. Patients with previous PCR-confirmed COVID19 were excluded, therefore 77 were finally included for analysis; 75 were liver transplant recipients, 1 was a combined liver-intestine and 1 a multivisceral transplant. All received their first vaccine dose between March and June 2021; 66,2% males, and the mean age was 56,3 years. All patients have a post-transplant follow up longer than 1 year (mean 6.6 years, median 5 years, range 1-23 years). Immune response after first, second and third doses were determined using three different spike (S)-S commercial ELISA kits and an in-house made anti nucleocapsid-protein (N) ELISA.

RESULTS

Following the three doses, 57.1 % (44/77) of the patients seroconverted, while 33/77 (42.9 %) did not present anti-SARS-CoV-2 antibodies. The seroconversion rate was different for each dose. We found that 5/27 (18.5 %) of transplant patients seroconverted after a single dose; 18/29 pts (62.0 %) had anti-SARS-Cov-2 antibodies after the second doses; and 18/21 pts (85.7 %) reached the seroconversion after the third doses. The proportion of seroconversion was significantly increased in the second doses regardless the response observed after the first doses (p = 0.012, Fisher's exact test), particularly when two doses of ChAdOx11 vaccine was administrated (p = 0.040, Chi-square). However, the comparisons of seroconversion rate between Sputnik V and ChAdOx11 vaccines showed no differences after the different vaccination doses. No significant statistical difference in patient́s gender, age, comorbidities, type of vaccine, post-transplant, or maintenance immunosuppressive therapy was found between responders and non-responders.

CONCLUSION

Despite having a lower seroconversion rate compared to the general population, viral-vector vaccines benefit SOTR patients increasing the seroconversion rate using at least two doses of vaccine. These results support the concept of developing tailor-made vaccination guidelines for this specific population. This analysis provides further support to safety and efficacy of viral-vector vaccines in liver and liver-intestine transplant patients.

摘要

背景

与慢性免疫抑制患者相比,不同的抗SARS-CoV-2疫苗在健康人群中引发免疫反应的能力并不相同。大多数评估抗SARS-CoV-2疫苗对实体器官移植受者(SOTR)影响的报告是使用基于mRNA的疫苗进行的。

目的

本研究旨在评估在我国阿根廷使用的非复制型载体疫苗(rAd26-rAd5(卫星五号)和ChAdOx11 nCoV-19(AZD1222)(阿斯利康-牛津))对一组肝移植和肝肠移植患者进行疫苗接种后的血清转化率。

方法

招募了103名肝移植和肝肠移植受者。排除先前PCR确诊为COVID-19的患者,因此最终纳入77例进行分析;75例为肝移植受者,1例为肝肠联合移植,1例为多脏器移植。所有患者均在2021年3月至6月期间接种了第一剂疫苗;男性占66.2%,平均年龄为56.3岁。所有患者移植后的随访时间均超过1年(平均6.6年,中位数5年,范围1 - 23年)。使用三种不同的刺突(S)-S商业ELISA试剂盒和自制的抗核衣壳蛋白(N)ELISA法测定第一剂、第二剂和第三剂疫苗后的免疫反应。

结果

接种三剂疫苗后,57.1%(44/77)的患者发生血清转化,而33/77(42.9%)的患者未出现抗SARS-CoV-2抗体。每剂疫苗后的血清转化率不同。我们发现,5/27(18.5%)的移植患者在单剂接种后发生血清转化;18/29例患者(62.0%)在第二剂接种后产生了抗SARS-CoV-2抗体;18/21例患者(85.7%)在第三剂接种后达到血清转化。无论第一剂接种后的反应如何,第二剂接种后的血清转化率均显著提高(p = 0.012,Fisher精确检验),尤其是在接种两剂ChAdOx11疫苗时(p = 0.040,卡方检验)。然而,在不同接种剂量后,卫星五号疫苗和ChAdOx11疫苗之间的血清转化率比较未显示出差异。在有反应者和无反应者之间,患者的性别、年龄、合并症、疫苗类型、移植后或维持免疫抑制治疗方面未发现显著统计学差异。

结论

尽管与普通人群相比血清转化率较低,但病毒载体疫苗使SOTR患者受益,使用至少两剂疫苗可提高血清转化率。这些结果支持为这一特定人群制定量身定制的疫苗接种指南的概念。该分析进一步支持了病毒载体疫苗在肝移植和肝肠移植患者中的安全性和有效性。

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