Immunoengineering

免疫工程

基本信息

批准号：
10702979
负责人：
Kaitlyn Sadtler
金额：
$ 64.14万
依托单位：
NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10702979
关键词：
2019-nCoV Adipocytes Admission activity Africa Age Antibodies Antibody Formation Award Biocompatible Materials Biological Markers Biomaterials Research Biomedical Engineering C57BL/6 Mouse COVID-19 vaccination Calendar Cells Cicatrix Clinical Color Communities Data Databases Dendritic Cells Drug usage Ear Evaluation Fatty acid glycerol esters Fibrosis Flow Cytometry Foreign Bodies General Population Genetic Growth High Prevalence Histologic Hospitalization Human Immune Immune response Immunity Immunocompromised Host Immunologics In Vitro Individual Injury MRL/MpJ Mouse Manuscripts Modeling Muscle National Institute of Biomedical Imaging and Bioengineering Natural regeneration Organ Patients Population Prevalence Publications Publishing Rare Diseases Rattus Research Personnel Resource Sharing Role Scientist Seroprevalences Services Southeastern Asia T-Cell Activation Testing Time Tissues Trauma United States United States National Institutes of Health Up-Regulation Vaccination Work breakthrough infection healing immune function immune self tolerance immunoengineering implantable device implantation interest lipid biosynthesis mouse model physical science programs recruit regenerative response seropositive tissue regeneration transcriptome sequencing

项目摘要

Analysis of SARS-CoV-2 Seroprevalence in the US Population and Rare Disease Patients Previously we established a range of antibody tests to evaluate SARS-CoV-2 seroprevalence (JoCI, 2021, Nat Comms 2021, JID 2021) in the US population (STM 2021, medRxiv) and abroad including Africa and Southeast Asia (CID 2022, JID 2021, EID 2022). We are continuing to study US seroprevalence over the course of a year from 2020 to 2021 and are finalizing the analysis of that study, which includes data on undiagnosed reinfections and undiagnosed vaccination breakthrough infections. We are also looking at seroprevalence in a population of rare disease patients during the same timeframe. We expect both of these studies to be submitted for publication by the end of this calendar year. Antibody production from SARS-CoV-2 vaccination in immunodeficient patients We have adapted our SARS-CoV-2 seroassays for evaluation of immune response to vaccination in immunocompromised/immunodeficient patients. Through this we have also transitioned our seroassays to the Bioengineering and Physical Sciences shared resource (BEPS) wherein any NIH scientist can request these to be completed in a for-service manner. We expect the first publication of this study to be submitted by the end of the calendar year. SARS-CoV-2 in trauma admits and correlation with drug use As our lab is interested in the immunologic responses to trauma and downstream effects on tissue growth and regeneration, we evaluated the intersection with SARS-CoV-2 through a seroprevalence evaluation. In this study we were able to show that trauma admits had a higher prevalence of SARS-CoV-2 in comparison to the general population. We also saw a correlation with drug usage, wherein individuals on depressants were less likely to be seropositive for SARS-CoV-2. We have preprinted this study and expect to submit this for publication by the end of 2022. Immunologic self-tolerance in trauma and biomaterial implantation As we finalize our work on SARS-CoV-2 we began our biomaterials research in earnest, and have preprinted our first biomaterials work wherein we describe a dendritic cell subset that appears to be critical in regulating the immune response to trauma. We showed both a putative mechanism of their recruitment, as well as the role of these cells in controlling T cell activation and minimizing further tissue damage after the initial trauma. Interactions between white fat and immunity after injury in a super healing mouse model The MRL/MpJ mouse is famous for being able to fully heal an ear punch in comparison to the C57BL/6 mouse which scars. We wanted to investigate the difference in immune responses to pro-regenerative versus pro-fibrotic materials in the MRL versus B6 models. We found a strong upregulation of adipogenesis in the MRL model with large, disperse numbers of white fat cells noted histologically, and white fat genetic programs upregulated as determined by RNAseq. We are currently evaluating the immunologic differences and hope to have this manuscript submitted by November 2022. Immune responses to trauma in a rat model In order to expand our findings to different species, we developed a flow cytometry panel to evaluate immune responses to muscle trauma in a rat model. We developed the largest flow cytometry panel currently published and used it to characterize immune cells in a muscle injury model in a rat. This manuscript was published in Cells, Tissues, and Organs in the Young Investigators Award issue. Adusei et al. CTO. Systemic responses to trauma in human patients at hospital admission As we expanded our analyses of immune responses to trauma in different species, we continued to develop our evaluation of human immune response to trauma. We evaluated systemic immune profile of trauma admits at the time of admission and we found several correlations with age, and are currently assembling a full database of biomarker data alongside clinical information of 1500 patients which we will be analyzing in the coming weeks.

美国人群和罕见疾病患者中 SARS-CoV-2 血清阳性率分析此前，我们建立了一系列抗体测试来评估美国人群（STM 2021，medRxiv）以及包括非洲和东南亚在内的国外人群（CID 2022，JID）中的 SARS-CoV-2 血清阳性率（JoCI，2021，Nat Comms 2021，JID 2021） 2021 年，开斋节 2022 年）。我们将继续研究 2020 年至 2021 年一年内美国的血清流行情况，并正在完成该研究的分析，其中包括未确诊的再感染和未确诊的疫苗接种突破感染的数据。我们还在研究同一时间范围内罕见疾病患者群体的血清阳性率。我们预计这两项研究将于今年年底提交发表。免疫缺陷患者通过接种 SARS-CoV-2 疫苗产生抗体我们已经调整了 SARS-CoV-2 血清测定法，用于评估免疫功能低下/免疫缺陷患者对疫苗接种的免疫反应。通过这一点，我们还将我们的血清测定转移到生物工程和物理科学共享资源 (BEPS)，其中任何 NIH 科学家都可以请求以服务方式完成这些测定。我们预计这项研究的第一份出版物将在今年年底提交。创伤承认中的 SARS-CoV-2 及其与药物使用的相关性由于我们的实验室对创伤的免疫反应以及对组织生长和再生的下游影响感兴趣，因此我们通过血清阳性率评估来评估与 SARS-CoV-2 的交叉。在这项研究中，我们能够证明，与普通人群相比，创伤患者的 SARS-CoV-2 患病率更高。我们还发现了与药物使用的相关性，其中服用抑制剂的个体出现 SARS-CoV-2 血清阳性的可能性较小。我们已经预印了这项研究，并预计在 2022 年底之前提交出版。创伤和生物材料植入中的免疫自我耐受当我们完成 SARS-CoV-2 的工作时，我们开始认真地进行生物材料研究，并预印了我们的第一份生物材料工作，其中我们描述了一个树突状细胞亚群，该亚群似乎对调节对创伤的免疫反应至关重要。我们展示了它们募集的假定机制，以及这些细胞在控制 T 细胞激活和最大限度地减少初始创伤后进一步组织损伤中的作用。超级愈合小鼠模型损伤后白色脂肪与免疫之间的相互作用与会留下疤痕的 C57BL/6 小鼠相比，MRL/MpJ 小鼠因能够完全治愈耳朵穿孔而闻名。我们想要研究 MRL 与 B6 模型中对促再生材料和促纤维化材料的免疫反应的差异。我们发现 MRL 模型中脂肪生成强烈上调，组织学上注意到大量分散的白色脂肪细胞，并且根据 RNAseq 确定白色脂肪遗传程序上调。我们目前正在评估免疫学差异，并希望在 2022 年 11 月之前提交这份手稿。大鼠模型对创伤的免疫反应为了将我们的发现扩展到不同的物种，我们开发了流式细胞术面板来评估大鼠模型对肌肉创伤的免疫反应。我们开发了目前已发表的最大的流式细胞术面板，并用它来表征大鼠肌肉损伤模型中的免疫细胞。这篇手稿发表在青年研究者奖的《细胞、组织和器官》杂志上。阿杜塞等人。首席技术官。人类患者入院时对创伤的全身反应随着我们扩大对不同物种对创伤的免疫反应的分析，我们继续发展对人类对创伤的免疫反应的评估。我们在入院时评估了创伤患者的全身免疫特征，发现了与年龄的一些相关性，目前正在收集一个完整的生物标志物数据数据库以及 1500 名患者的临床信息，我们将在未来几周内对其进行分析。