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免疫抑制个体和健康个体接种单价奥密克戎JN.1适应性mRNA新冠疫苗后的中和抗体及T细胞针对刺突蛋白的反应

Neutralizing Antibody and T-Cell Spike Targeted Responses Following Receipt of a Monovalent Omicron JN.1-Adapted mRNA COVID-19 Vaccine in Immunosuppressed and Healthy Individuals.

作者信息

Sánchez-Simarro Ángela, Carretero Diego, Grau Brayan, Martínez-Pérez Mireya, Albert Eliseo, Giménez Estela, Colomer Ester, Panizo Nayara, Hernani Rafael, Espert Aida Hernández, Solano Carlos, Piñana José Luis, Górriz José Luis, Geller Ron, Navarro David

机构信息

Microbiology Service, Hospital Clínico Universitario de Valencia, INCLIVA Health Research Institute, Valencia, Spain.

Institute for Integrative Systems Biology (I2SysBio), Universitat de Valencia-CSIC, Valencia, Spain.

出版信息

J Med Virol. 2025 Jun;97(6):e70463. doi: 10.1002/jmv.70463.

Abstract

We evaluated homologous neutralizing antibody (NtAb) and T-cell responses after receipt of a JN.1-adapted mRNA vaccine in a mixed population comprising healthy controls (HC) (n = 15), end-stage chronic kidney disease (CKD) patients (n = 17), and allogeneic hematopoietic stem cell transplant recipients (allo-HCT) (n = 13). Most participants (42/45) were SARS-CoV-2-experienced at the time of immunological testing. JN.1-spike-binding NtAbs were measured with a vesicular stomatitis virus pseudotype-based neutralization assay, whereas interferon (IFN)-γ-producing spike-directed CD4 or CD8 T-cell frequencies were enumerated using flow cytometry for intracellular staining. All participants had detectable JN.1 NtAbs at baseline; overall, JN.1-NtAb levels increased in HC (median, ∼1 log; p < 0.001) and CKD patients (median, 0.8 log; p = 0.06) but not in allo-HCT (p = 0.10). JN.1-NtAb titers measured after vaccination were significantly higher in HC than in CKD and allo-HCT (p = 0.01). The number of participants exhibiting detectable JN.1 T-cell responses did not significantly increase following booster vaccination in any of the study groups. Likewise, receipt of the Omicron JN.1 vaccine failed to significantly boost SARS-CoV-2 JN.1 CD8 and CD4 T-cell frequencies in any study groups. Nevertheless, trends in JN.1 T-cell frequencies following the JN-1 booster varied widely on an individual basis. JN.1 T-cell frequencies following JN.1 vaccination were comparable across study groups. Our results could have implications for the development of vaccines for future SARS-CoV-2 variants and the optimization of booster vaccination policies in allogeneic hematopoietic transplant recipients and patients with end-stage chronic kidney diseases.

摘要

我们在一个混合人群中评估了接种JN.1适配mRNA疫苗后的同源中和抗体(NtAb)和T细胞反应,该混合人群包括健康对照者(HC)(n = 15)、终末期慢性肾病(CKD)患者(n = 17)和异基因造血干细胞移植受者(allo-HCT)(n = 13)。大多数参与者(42/45)在进行免疫检测时曾感染过SARS-CoV-2。使用基于水疱性口炎病毒假型的中和试验测量JN.1刺突结合NtAb,而使用流式细胞术进行细胞内染色来计数产生干扰素(IFN)-γ的刺突定向CD4或CD8 T细胞频率。所有参与者在基线时均可检测到JN.1 NtAb;总体而言,HC组(中位数,约1 log;p < 0.001)和CKD患者组(中位数,0.8 log;p = 0.06)的JN.1-NtAb水平升高,但allo-HCT组未升高(p = 0.10)。接种疫苗后测量的JN.1-NtAb滴度在HC组显著高于CKD组和allo-HCT组(p = 0.01)。在任何研究组中,加强接种后出现可检测到的JN.1 T细胞反应的参与者数量均未显著增加。同样,在任何研究组中,接种奥密克戎JN.1疫苗均未能显著提高SARS-CoV-2 JN.1 CD8和CD4 T细胞频率。然而,JN.1加强接种后JN.1 T细胞频率的趋势在个体间差异很大。JN.1接种后各研究组的JN.1 T细胞频率相当。我们的结果可能对未来SARS-CoV-2变异株疫苗的开发以及异基因造血移植受者和终末期慢性肾病患者加强接种策略的优化具有启示意义。

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