mRNA 疫苗接种 COVID-19 对有 SARS-CoV-2 既往感染的肺移植受者诱导持久的 SARS-CoV-2 特异性抗体和 T 细胞。

mRNA-based COVID-19 vaccination of lung transplant recipients with prior SARS-CoV-2 infection induces durable SARS-CoV-2-specific antibodies and T cells.

机构信息

Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, the Netherlands.

Department of Viroscience, Erasmus University Medical Center, Rotterdam, the Netherlands.

出版信息

Vaccine. 2024 Oct 24;42(24):126250. doi: 10.1016/j.vaccine.2024.126250. Epub 2024 Sep 2.

Abstract

Lung transplant recipients (LTRs) are particularly at risk of developing severe coronavirus disease-2019 (COVID-19), but are also difficult to protect by vaccination due to their immunocompromised state. Here, we investigated the immunogenicity of mRNA-based COVID-19 vaccines in LTRs who had a prior natural SARS-CoV-2 infection. At a median of 184 days after SARS-CoV-2 infection, LTRs were vaccinated twice with the mRNA-1273 COVID-19 vaccine, with a 28-day interval. Blood samples were obtained pre-vaccination, 28 days after the first dose, and 28 days and 6 months after the second dose. Spike (S-) and nucleocapsid (N-) specific antibodies were measured, as well as neutralization of the ancestral and Omicron BA.5 variant. S-specific T cell responses were evaluated using IFN-γ ELISpot,IGRA, and activation markers by flow cytometry. Phenotyping of T cells was performed by using high-resolution spectral flow cytometry. Most LTRs with prior infection had detectable S-specific antibodies and T cells at baseline. After the first vaccination, S-specific antibody levels increased significantly; an additional increase was observed after the second vaccination. N-specific antibodies decreased during the study period, indicative of the fact that no further breakthrough infections occurred. An increase in IFN-γ producing T cells was observed after the first vaccination, but no additional boost could be detected after the second vaccination. Antibody levels and virus-specific T cell responses remained significantly higher compared to pre-vaccination levels at 6 months post-vaccination, indicating an additive and durable effect of vaccination after infection in LTRs. Neutralizing antibodies were detected against the ancestral strain and retained cross-reactivity with Omicron BA.5, albeit at lower levels. Moreover, the quantity and phenotype of SARS-CoV-2 spike-specific T cells were similar in LTRs compared to controls with hybrid immunity. In conclusion, mRNA-based COVID-19 vaccines are immunogenic in LTRs with prior immunity, and antibody and T cell responses are durable up to 6 months post-vaccination.

摘要

肺移植受者(LTR)特别容易发生严重的 2019 年冠状病毒病(COVID-19),但由于其免疫功能低下,也难以通过疫苗接种进行保护。在这里,我们研究了先前感染过 SARS-CoV-2 的 LTR 中基于 mRNA 的 COVID-19 疫苗的免疫原性。在 SARS-CoV-2 感染后中位数为 184 天,LTR 用 mRNA-1273 COVID-19 疫苗进行了两次接种,间隔 28 天。在接种前、第一剂后 28 天以及第二剂后 28 天和 6 个月采集血样。测量了刺突(S)和核衣壳(N)特异性抗体,以及对原始和奥密克戎 BA.5 变体的中和作用。使用 IFN-γ ELISpot、IGRA 和流式细胞术的激活标志物评估 S 特异性 T 细胞反应。通过使用高分辨率光谱流式细胞术对 T 细胞进行表型分析。大多数有既往感染的 LTR 在基线时具有可检测的 S 特异性抗体和 T 细胞。接种第一针后,S 特异性抗体水平显著增加;接种第二针后又有增加。研究期间 N 特异性抗体下降,表明没有发生进一步的突破性感染。接种第一针后观察到 IFN-γ 产生 T 细胞增加,但接种第二针后未检测到额外增加。接种后 6 个月,抗体水平和病毒特异性 T 细胞反应仍显著高于接种前水平,表明 LTR 感染后接种具有累加和持久的效果。检测到针对原始株的中和抗体,并保留与奥密克戎 BA.5 的交叉反应性,尽管水平较低。此外,与具有混合免疫力的对照相比,LTR 中 SARS-CoV-2 刺突特异性 T 细胞的数量和表型相似。总之,先前具有免疫性的 LTR 中,基于 mRNA 的 COVID-19 疫苗具有免疫原性,抗体和 T 细胞反应在接种后 6 个月内持久。

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