Vaccine-Induced Immunity against Influenza in Frailty

虚弱者疫苗诱导的流感免疫力

• 批准号: 7152114
• 负责人: Sean Xiao Leng
• 金额: $ 14.06万
• 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/7152114
• 关键词: active immunization; antibody titering; cellular immunity; clinical research; cytotoxic T lymphocyte; frail elderly; helper T lymphocyte; human old age (65+); human subject; humoral immunity; immune response; immunopharmacology; immunosenescence; influenza; influenza vaccines; interferon gamma; interleukin 2; patient oriented research; phenotype

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 Sean Leng 表现出了成为临床/转化衰老研究领导者的巨大潜力和无与伦比的决心。他接受过免疫学和分子病毒学、细胞因子研究和内科方面的高级培训。在约翰·霍普金斯大学获得老年医学和老年学临床和研究奖学金后，他于 2002 年被聘为该院讲师，并于 2003 年晋升为医学助理教授。他是 NIA 和 NIA 短期 R21 项目的获得者。约翰霍普金斯大学的内部研究奖。 Leng 博士得到了老年病学家和流行病学家 Linda Fried 博士（老年医学和老年学部及老龄与健康中心教授兼主任）以及免疫学家 Noel Rose 博士（自身免疫性疾病研究中心教授兼主任）的大力指导。 。他们将为他提供广泛的资源和令人兴奋的跨学科环境，以开启他在转化衰老研究方面的独立学术生涯。 Leng 博士的研究兴趣是衰弱，这是一种常见的老年综合症，其特征是多个生理系统失调，并且更容易受到包括感染在内的压力源的影响，从而导致老年人出现严重的不良健康后果。根据冷博士当前研究的初步结果，该项目提议对社区居住的体弱和年龄匹配的非体弱老年人进行流感免疫试点研究。通过这种临床上成熟的体内免疫挑战，我们将描述体弱老年人的免疫失调特征，并根据以下具体目标转化其在临床导入背景下的影响：1）确定体弱老年人是否具有通过病毒测量的体液免疫受损-特异性抗体瓦片； 2) 通过抗原特异性 CD4+ 和 CD8+ T 细胞的数量、细胞内 IFN-γ 和 IL-2 的产生以及细胞毒性 T 淋巴细胞 (CTL) 的数量来确定体弱的老年人是否存在疫苗诱导的细胞介导免疫 (CMI) 受损） 功能。冷博士还将评估疫苗接种前特定T细胞表型CD8+CD28-T细胞的数量与疫苗诱导的CMI的关系； 3) 描述在疫苗接种后季节，与非体弱对照者相比，接种疫苗的体弱老年人的流感感染率及其并发症（肺炎、住院和死亡）是否增加。作为我们最初的转化工作，该项目将提高我们评估和增强免疫功能的能力，并最终预防体弱老年人的相关不良健康后果，包括流感感染及其破坏性并发症。 冷博士在临床老年医学和基础免疫学/分子病毒学和细胞因子研究方面的双重培训、强有力的指导、精心设计的职业发展计划、支持性环境和新颖的研究计划将为他提供发展成为高度专业人士所需的经验和工具。成功的独立医生/老年病学家科学家。