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骨化二醇通过上调促进记忆性T细胞反应的基因来提高ChAdOx1 nCoV-19疫苗的效力。

Calcifediol boosts efficacy of ChAdOx1 nCoV-19 vaccine by upregulating genes promoting memory T cell responses.

作者信息

Saroha Himanshu Singh, Bhat Swati, Das Liza, Dutta Pinaki, Holick Michael F, Sachdeva Naresh, Marwaha Raman Kumar

机构信息

Department of Endocrinology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, 160012, India.

Department of Section on Endocrinology, Diabetes, Nutrition & Weight Management, Department of Medicine, School of Medicine, Boston University, Boston, MA, USA.

出版信息

NPJ Vaccines. 2024 Jun 20;9(1):114. doi: 10.1038/s41541-024-00909-w.

DOI:10.1038/s41541-024-00909-w
PMID:38902265
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11190216/
Abstract

The ChAdOx1 nCoV-19 (COVISHIELD) vaccine has emerged as a pivotal tool in the global fight against the COVID-19 pandemic. In our previous study eligible subjects were supplemented with calcifediol, a direct precursor to the biologically active form of vitamin D, calcitriol with an objective to enhance the immunogenicity of the COVISHIELD vaccine. Herein we investigated the effects of calcifediol supplementation on gene expression profiles in individuals who received the COVISHIELD vaccine. Peripheral blood mononuclear cells were isolated from vaccinated individuals with and without calcifediol supplementation at baseline, 3rd and 6th month, and the gene expression profiles were analyzed using high-throughput sequencing. The results revealed distinct patterns of gene expression associated with calcifediol supplementation, suggesting potential molecular mechanisms underlying the beneficial effects of calcifediol in improving the efficacy of COVISHIELD vaccine via augmentation of T cell activation, proliferation and T cell memory responses. Additionally, there was upregulation of NOD like receptor, JAK/STAT and TGF beta signaling pathways. Calcifediol supplementation in vaccinated individuals also downregulated the pathways related to the Coronavirus disease. Taken together, our findings provide valuable insights into the interplay between vitamin D receptor (VDR) signaling and vaccine-induced immune responses and offer another approach in improving vaccination induced antiviral responses.

摘要

ChAdOx1 nCoV-19(COVISHIELD)疫苗已成为全球抗击新冠疫情的关键工具。在我们之前的研究中,符合条件的受试者补充了骨化二醇,它是生物活性形式的维生素D(骨化三醇)的直接前体,目的是增强COVISHIELD疫苗的免疫原性。在此,我们研究了补充骨化二醇对接种COVISHIELD疫苗个体基因表达谱的影响。在基线、第3个月和第6个月,从补充和未补充骨化二醇的接种疫苗个体中分离外周血单核细胞,并使用高通量测序分析基因表达谱。结果揭示了与补充骨化二醇相关的独特基因表达模式,提示骨化二醇通过增强T细胞活化、增殖和T细胞记忆反应来提高COVISHIELD疫苗效力的潜在分子机制。此外,NOD样受体、JAK/STAT和TGF-β信号通路存在上调。接种疫苗个体补充骨化二醇还下调了与冠状病毒病相关的通路。综上所述,我们的研究结果为维生素D受体(VDR)信号传导与疫苗诱导的免疫反应之间的相互作用提供了有价值的见解,并为改善疫苗诱导的抗病毒反应提供了另一种方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41f4/11190216/69b6e60212ec/41541_2024_909_Fig7_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41f4/11190216/69b6e60212ec/41541_2024_909_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41f4/11190216/321ab8994836/41541_2024_909_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41f4/11190216/dc101b2fbcf0/41541_2024_909_Fig2_HTML.jpg
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