Vitamin D and Immunosenescence in Older Long-Term Care Residents

简介（由申请人提供）：候选人：Adit Ginde，医学博士，公共卫生硕士，科罗拉多大学丹佛分校（UCD）急诊医学助理教授。他之前有公共卫生硕士学位和研究奖学金培训，他的早期研究生涯主要集中在维生素D和急性呼吸道感染（ARI）的观察性研究。他寻求从机构KL2奖过渡到比森职业发展奖，专注于维生素D在与年龄相关的免疫功能下降中的作用，特别是老年人对感染和疫苗的反应。导师/环境：主要的导师，罗伯特·施瓦茨，医学博士，是老年医学的部门负责人和UCD老龄中心主任。免疫学的共同导师，医学博士Myron Levin是UCD的医学和儿科学教授，他的研究重点是描述和改善对流感和带状疱疹疫苗的反应。两人都是资金充足的NIH临床研究员，并指导了许多年轻教师在衰老和免疫学研究方面取得成功的独立事业。培训：建议的比森职业发展计划建立在之前的奖学金和早期职业发展奖项的经验基础上，重点关注需要额外培训的三个主要主题领域：1)转化和介入研究设计；2)老龄/养老院研究；3)临床免疫学。Ginde博士提出了密集的专题指导，重点课程/研讨会和指导研究。研究：感染在老年人中很常见，导致医疗保健利用率和发病率增加。疫苗提高宿主对病原体的防御能力，减少常见感染的发生率、严重程度和持续时间。然而，对传染性病原体的免疫反应和疫苗的有效性随着年龄的增长而下降。维生素D补充剂改善老年人对病原体和疫苗反应的能力此前尚未在临床试验中进行过研究。在老年人（年龄50 ~ 60岁）长期护理居民中每月口服高剂量维生素D3与标准剂量维生素D3补充的临床试验背景下，我们提出以下具体目标：1)衡量每月口服高剂量维生素D3补充（相当于3,000-4,000 IU/天）与标准剂量维生素D3补充（400-1,000 IU/天）在预防200名老年人(年龄？？60岁)长期护理居民；2)通过补充维生素D3剂量和接种前血清25-羟基维生素D水平，确定对灭活季节性流感疫苗特异性体液免疫应答的差异；3)通过补充维生素D3剂量和接种前25-羟基维生素D水平确定对减毒带状疱疹活疫苗特异性细胞介导免疫应答的差异。摘要：本创新研究计划；来自老年病、传染病、免疫学和疫苗专家的强大指导；和拟议的职业发展经验将帮助Ginde博士成为干预措施的主要研究者，以改善免疫衰老和减少老年人的感染负担。

DESCRIPTION (provided by applicant): Candidate: Adit Ginde, MD, MPH is an Assistant Professor of Emergency Medicine at University of Colorado Denver (UCD). He has prior MPH and research fellowship training, and his early research career has focused on observational studies in vitamin D and acute respiratory infection (ARI). He seeks to transition from his institutional KL2 Award to this Beeson Career Development Award to focus on the role of vitamin D in the age related decline in immune function and specifically, response to infection and vaccine in older adults. Mentors/Environment: The primary mentor, Robert Schwartz, MD, is the Division Head of Geriatric Medicine and Director of the UCD Center on Aging. The co-mentor for immunology, Myron Levin, MD, is Professor of Medicine and Pediatrics at UCD, whose research has focused on characterizing and improving response to influenza and herpes zoster vaccines. Both are well-funded NIH clinical investigator and have mentored numerous junior faculty to successful independent careers in aging and immunology research. Training: The proposed Beeson career development plan builds on prior experience from fellowship and early career development awards to focus on three primary topical areas that require additional training: 1) Translational and Interventional Study Design; 2) Aging/Nursing Home Research; and 3) Clinical Immunology. Dr. Ginde proposes intensive topical mentorship, focused coursework/seminars, and mentored research. Research: Infections are common in older adults resulting in increased healthcare utilization and morbidity. Vaccines improve host defense against pathogens and reduce the incidence, severity, and duration of common infections. However, the immune response to infectious pathogens and effectiveness of vaccines decline with advancing age. The ability of vitamin D supplementation to improve response to pathogens and vaccines in older adults has not been previously investigated in a clinical trial. In the context of a clinical trial of monthly oral high-dose vitamin D3 supplementation vs. standard dose vitamin D3 supplementation in older (age > 60 years) long-term care residents, we propose the following specific aims: 1) Measure the efficacy of high dose monthly oral high-dose vitamin D3 supplementation (equivalent to 3,000-4,000 IU/day) compared to standard dose vitamin D3 supplementation (400-1,000 IU/day) in prevention of ARIs in 200 older (age ?? 60 years) long-term care residents; 2) Determine the difference in specific humoral immune response to the inactive seasonal influenza vaccine by vitamin D3 supplementation dose and pre-vaccination serum 25- hydroxyvitamin D levels; 3) Determine the difference in specific cell-mediated immune response to the live, attenuated zoster vaccine by vitamin D3 supplementation dose and pre-vaccination 25-hydroxyvitamin D levels. Summary: This innovative research plan; strong mentorship from geriatrics, infectious disease, immunology, and vaccine experts; and proposed career development experience will help Dr. Ginde become a leading investigator of interventions to improve immunosenescence and reduce the burden of infection in older adults. PUBLIC HEALTH RELEVANCE: As life expectancy increases, the increased incidence and severity of infection associated with aging has become a critical public health issue. Infection impacts the function, independence, and survival of older adults, and is a major contributor to healthcare utilization and costs. Through the proposed study, we will learn about the role of clinical interventions, particularly vitamin D, to improve the immune response to infection and vaccines, and ultimately reduce the incidence and severity of infection in older adults.