Vitamin D and Immunosenescence in Older Long-Term Care Residents

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急诊医学助理教授。他以前接受过公共卫生硕士和研究奖学金培训，早期的研究生涯侧重于维生素D和急性呼吸道感染(ARI)的观察性研究。他寻求从他的机构KL2奖过渡到本届比森职业发展奖，以关注维生素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：主要导师罗伯特·施瓦茨，医学博士，老年医学部主任和UCD老龄中心主任。免疫学的共同导师，医学博士Myron Levin是UCD的医学和儿科教授，他的研究重点是表征和改善对流感和带状疱疹疫苗的反应。两人都是资金雄厚的NIH临床研究员，并指导了许多初级教员在老龄化和免疫学研究方面成功地独立工作。培训：拟议的Beeson职业发展计划建立在奖学金和早期职业发展奖的先前经验基础上，专注于需要额外培训的三个主要主题领域：1)翻译和介入研究设计；2)老龄化/疗养院研究；以及3)临床免疫学。金德博士建议进行密集的专题指导、重点课程/研讨会和有指导的研究。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。疫苗提高了宿主对病原体的抵抗力，降低了常见感染的发生率、严重性和持续时间。然而，随着年龄的增长，对感染性病原体的免疫反应和疫苗的效力都会下降。补充维生素D改善老年人对病原体和疫苗的反应的能力之前还没有在临床试验中进行过研究。在一项在老年(60岁)长期护理居民中每月口服大剂量维生素D3补充剂与标准剂量维生素D3补充剂的临床试验的背景下，我们提出了以下具体目标：1)在200名老年(60岁)长期护理居民中，衡量每月高剂量口服高剂量维生素D3补充剂(相当于3,000-4,000 IU/天)与标准剂量维生素D3补充剂(400-1,000 IU/天)在预防ARIS方面的有效性；2)通过补充维生素D3剂量和接种前血清25-羟基维生素D水平来确定对季节性流感灭活疫苗的特异性体液免疫应答的差异；3)通过补充维生素D3剂量和接种前的25-羟基维生素D水平来确定对减毒活带状疱疹疫苗的特异性细胞免疫应答的差异。摘要：这一创新的研究计划；老年病学、传染病、免疫学和疫苗专家的强大指导；以及拟议的职业发展经验，将帮助金德博士成为改善免疫衰老和减轻老年人感染负担的干预措施的领先调查者。

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.