Engineering the Skin Immune System to Induce Systemic Immune Responses

改造皮肤免疫系统以诱导全身免疫反应

基本信息

批准号：
10363729
负责人：
Louis D Falo
金额：
$ 65.17万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-03-04 至 2026-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10363729
关键词：
2019-nCoV Address Adjuvant Age Antibodies Antibody Response Antigen-Presenting Cells Antigens Biological Markers Biology Bronchoalveolar Lavage CD8-Positive T-Lymphocytes COVID-19 COVID-19 vaccine Cell physiology Cellular Immunity Clinical Clinical Trials Combined Vaccines Cutaneous Data Dermatology Development Disease Dose Elderly Engineered skin Engineering Funding Generations Goals Health Human Immune Immune response Immune system Immunity Immunization Immunobiology Immunologics Immunomodulators In Situ Injections Innate Immune Response Longevity Lung Lymphoid Tissue Methods Mus Natural Immunity Needles Organ Phase I/II Clinical Trial Predisposition Prevention Protein Subunits Publishing Regulation SARS-CoV-2 antigen SARS-CoV-2 immunity Safety Skin Skin Aging Skin Cancer Spleen Subunit Vaccines T-Lymphocyte Technology Translations United States National Institutes of Health Vaccination Vaccines adaptive immune response aged base clinical application clinical translation design draining lymph node experience immune function immunoengineering immunogenicity immunoregulation immunosenescence improved innate immune mechanisms neutralizing antibody next generation novel pathogen peripheral blood rational design targeted delivery translational study vaccination strategy vaccine delivery vaccine development vaccine efficacy vaccine response

项目摘要

PROJECT SUMMARY / ABSTRACT: The skin functions as a potent immune organ, rendering the readily accessible cutaneous microenvironment an attractive target that can be locally engineered to induce and regulate systemic immune responses. Increasing age is associated with changes in immune function (immunosenescence) that result in increased susceptibility to diseases and poor vaccine responses in older adults. This proposal is designed to bring together very recent and significant advances in dermatology and skin biology to address critical problems in human health. Here, we specifically focus on the skin microenvironment and strategies for cutaneous immunomodulation. The overall approach is to utilize a clinically applicable dissolvable microneedle array delivery platform we have developed to locally engineer the highly adaptive and immunoresponsive skin microenvironment. Specifically, we propose to modulate local immune regulatory circuits in the skin to enable the induction and regulation of systemic immune responses. The studies we propose will investigate the effect of locally delivered immune modulators on the mechanisms underlying cutaneous immune regulation in young and aged skin. Importantly, our studies include translational studies using living human skin to enable the rapid advancement of novel cutaneous immunomodulation strategies into clinical trials. The proposed studies will result in a better understanding of skin immunobiology specifically relevant to the development of safe and predictable skin immunoengineering strategies to regulate systemic immune responses across the lifespan.

项目摘要/摘要：皮肤作为一个强大的免疫器官，使皮肤易于接触微环境是一个有吸引力的目标，可以通过局部工程来诱导和调节全身免疫反应。年龄的增长与免疫功能的变化有关（免疫衰老）导致疾病易感性增加和疫苗质量较差老年人的反应。该提案旨在汇集最近且重要的皮肤病学和皮肤生物学的进步，以解决人类健康的关键问题。在这里，我们特别关注皮肤微环境和皮肤免疫调节策略。总体方法是利用临床适用的可溶性微针阵列递送我们开发的平台用于本地设计高度适应性和免疫反应性的皮肤微环境。具体来说，我们建议调节局部免疫调节回路皮肤能够诱导和调节全身免疫反应。我们的研究提议将研究局部递送的免疫调节剂对该机制的影响年轻和老年皮肤的潜在皮肤免疫调节。重要的是，我们的研究包括使用活人皮肤进行转化研究，以实现新型皮肤的快速发展免疫调节策略进入临床试验。拟议的研究将带来更好的结果了解皮肤免疫生物学，特别是与安全和开发相关的皮肤免疫生物学可预测的皮肤免疫工程策略来调节全身免疫反应寿命。