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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：
10561663
负责人：
Louis D Falo
金额：
$ 66.25万
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/10561663
关键词：
2019-nCoV Address Adjuvant Age Antibodies Antibody Response Antigen-Presenting Cells Antigens 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 Inflammatory Injections Innate Immune Response Learning Longevity Lung Lymphoid Tissue Methods Mus Natural Immunity Needles Organ Phase I/II Clinical Trial Predisposition Prevention Protein Subunits Publishing Regulation Reproducibility SARS-CoV-2 antigen SARS-CoV-2 immunity Safety Skin Skin Aging Skin Cancer Spleen Subunit Vaccines T-Lymphocyte Translations United States National Institutes of Health Vaccination Vaccines adaptive immune response aged biomarker identification 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 technology platform 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：