Vaccine-Induced Immunity against Influenza in Frailty

虚弱者疫苗诱导的流感免疫力

• 批准号: 7918111
• 负责人: Sean Xiao Leng
• 金额: $ 15.92万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7918111
• 关键词: Address; Age; Aging; Antibodies; Antigens; Autoimmune Diseases; Award; Biological; CD28 gene; CD8B1 gene; Cell Count; Cellular Immunity; Cessation of life; Characteristics; Clinical; Clinical Research; Clinical effectiveness; Communities; Coupled; Cytotoxic T-Lymphocytes; Data; Development; Doctor of Philosophy; Elderly; Environment; Epidemiologist; Faculty; Fellowship; Frail Elderly; Frail Older Adults; Funding Mechanisms; Future; Geriatrics; Gerontology; Goals; Health; Hospitalization; Humoral Immunities; Immune; Immune system; Immunologics; Immunologist; Immunology; Impairment; Infection; Inflammation; Influenza; Influenza vaccination; Interferons; Interleukin-2; Interleukin-6; Internal Medicine; Investigation; Knowledge; Lead; Life; Lymphocyte Function; Measures; Medicine; Memory; Mentorship; Molecular; Molecular Virology; Older Population; Outcome; Peripheral Blood Mononuclear Cell; Phenotype; Physicians; Physiological; Pneumonia; Predisposition; Prevention strategy; Production; Recruitment Activity; Research; Research Personnel; Research Project Grants; Resources; Risk; Rosa; Scientist; Seasons; Syndrome; System; T-Lymphocyte; Technology; Testing; Training; Translating; Vaccinated; Vaccination; Vaccines; Viral; Virus Diseases; adverse outcome; base; career; career development; cytokine; design; disability; experience; frailty; high risk; immune function; improved; in vivo; insight; instructor; interest; mortality; novel; prevent; professor; programs; senescence; stressor; tool; vaccine-induced immunity

DESCRIPTION (provided by applicant): Sean Leng, MD PhD, has demonstrated great promise, and unsurpassed determination, to become a leader in clinical / translational aging research. He has had advanced training in Immunology and Molecular Virology, Cytokine Research, and Internal Medicine. After a clinical and research fellowship in Geriatric Medicine and Gerontology at Johns Hopkins, he was recruited to its faculty as an Instructor in 2002 and was promoted to Assistant Professor of Medicine in 2003. He is a recipient of a short-term R21 from NIA and an internal research award at Johns Hopkins. Dr. Leng has strong mentorship from geriatrician and epidemiologist Dr. Linda Fried, Professor and Director of the Division of Geriatric Medicine and Gerontology and Center on Aging and Health, and from immunologist Dr. Noel Rose, Professor and Director of Center for Autoimmune Disease Research. They will provide him with extensive resources and a stimulating interdisciplinary environment to launch his independent academic career in translational aging research. Dr. Leng's research interest is in frailty, a common geriatric syndrome characterized by dysregulations in multiple physiologic systems and increased vulnerability to stressors, including infections, that result in severe adverse health outcomes in older adults. Based on the preliminary findings from Dr. Leng's current research, this project proposes a pilot influenza immunization study in community-dwelling frail and age-matched non-frail older adults. With this clinically well-established in vivo immune challenge, we will characterize immune dysregulation of frail older adults and translate its implications in the context of clinical import under the following specific aims: 1) Determine whether frail older adults have impaired humoral immunity measured by viral-specific antibody tilers; 2) Determine whether frail older adults have impairment in vaccine-induced cell-mediated immunity (CMI) measured by number of antigen-specific CD4+ and CD8+ T cells, intracellular production of IFN-y and IL-2, and cytotoxic T lymphocyte (CTL) function. Dr. Leng will also evaluate the relationship of pre-vaccination number of specific T cell phenotype, CD8+CD28-T cells, with vaccine-induced CMI; 3) To delineate whether vaccinated frail older adults have increased rate of influenza infection and its complications (pneumonia, hospitalization, and death), compared to non-frail controls, during the post-vaccination season. As our initial translational effort, this project will improve our ability to evaluate and strengthen immune function, and ultimately prevent related adverse health outcomes, including influenza infection and its devastative complications, for frail older adults. Dr. Leng's dual training in clinical geriatric medicine and basic immunology/molecular virology and cytokine research, strong mentorship, carefully designed career development program, supportive environment, and novel research plan will give him the experience and tools that he needs to develop into a highly successful, independent physician/geriatrician-scientist.

描述（由申请人提供）：医学博士学位的肖恩·伦（Sean Leng）表现出了巨大的希望和无与伦比的决心，成为临床 /转化衰老研究的领导者。他已经接受了免疫学和分子病毒学，细胞因子研究和内科的高级培训。经过约翰·霍普金斯（Johns Hopkins）的老年医学和老年病学临床和研究奖学金之后，他于2002年被招募为教师，并于2003年被晋升为医学助理教授。他获得了NIA的短期R21，并获得了约翰·霍普金斯（Johns Hopkins）的内部研究奖。 Leng博士拥有老年医生和流行病学家琳达·弗里德（Linda Fried）博士，老年医学和老年医学和衰老与健康中心的教授兼主任，以及免疫学家诺埃尔·罗斯（Noel Rose）博士，自动免疫疾病研究中心主任兼主任诺埃尔·罗斯（Noel Rose）博士。他们将为他提供广泛的资源和刺激性的跨学科环境，以启动他在翻译衰老研究方面的独立学术生涯。 Leng博士的研究兴趣是脆弱的，这是一种常见的老年综合征，其特征是多种生理系统中的失调，增加了对压力源（包括感染）的脆弱性，导致老年人严重不良健康。根据Leng博士当前研究的初步发现，该项目提出了一项试验性流感的免疫研究，该研究在社区贫困和年龄匹配的非怪异老年人中进行。借助这种临床良好的体内免疫攻击，我们将表征对脆弱的老年人的免疫失调，并在以下具体目的下在临床进口的背景下转化其含义：1）确定脆弱的老年人是否受到了通过病毒特异性抗体剂量测量的体液免疫； 2）确定通过抗原特异性CD4+和CD8+ T细胞的疫苗诱导的细胞介导的免疫（CMI）的脆弱老年人是否有损害，IFN-Y-Y和IL-2以及细胞毒性T淋巴细胞（CTL）功能的细胞内产生。 Leng博士还将评估特定T细胞表型CD8+CD28-T细胞的疫苗接种次数与疫苗诱导的CMI的关系； 3）在疫苗接种后季节，与非网络对照相比，与非肉体对照相比，要描绘出接种脆弱的老年人的流感感染率及其并发症及其并发症及其并发症及其并发症的发生率是否增加。作为我们最初的翻译工作，该项目将提高我们评估和增强免疫功能的能力，并最终防止与脆弱的老年人相关的不良健康结果，包括流感感染及其破坏性并发症。 Leng博士在临床老年医学和基本免疫学/分子病毒学和细胞因子研究，强大的指导，精心设计的职业发展计划，支持环境以及新颖的研究计划方面的双重培训将为他带来一项非常成功的，独立的医生/老年人/老年人科学家所需的经验和工具。

项目成果

An international model for geriatrics program development in China: the Johns Hopkins-Peking Union Medical College experience.

中国老年医学项目发展的国际模式：约翰霍普金斯大学-北京协和医学院的经验。

• DOI: 10.1111/j.1532-5415.2010.02927.x
• 发表时间: 2010
• 期刊: Journal of the American Geriatrics Society
• 影响因子: 6.3
• 作者: Leng,SeanX;Tian,Xinping;Liu,Xiaohong;Lazarus,Gerald;Bellantoni,Michele;Greenough,William;Fried,LindaP;Shen,Ti;Durso,SamuelC
• 通讯作者: Durso,SamuelC

Frailty, inflammation, and immunity.

• 发表时间: 2011-06
• 期刊: Aging and disease
• 影响因子: 7.4
• 作者: Huifen Li;B. Manwani;S. Leng