Protecting Patients with Glomerular Disease from Vaccine-Preventable Infections

保护肾小球疾病患者免受疫苗可预防的感染

• 批准号: 10571899
• 负责人: Dorey Glenn
• 金额: $ 20.14万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-02-15 至 2027-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10571899
• 关键词: Acceleration; Address; Adult; Advisory Committees; Age; Antibiotics; Antibodies; Antibody titer measurement; Attenuated; Biological Assay; Biopsy; Cause of Death; Cell physiology; Characteristics; Child; Clinical; Communicable Diseases; Complement; Data; Data Analyses; Databases; Development; Disease; Effectiveness; Epidemiology; Exposure to; Foundations; Frequencies; Goals; Guidelines; Healthcare; IgG Deficiency; Immune; Immune response; Immunity; Immunoglobulins; Immunosuppression; Impairment; Incidence; Individual; Infection; Infection prevention; Influenza; Kidney Diseases; Lead; Lower Respiratory Tract Infection; Measurement; Measures; Mediating; Mentorship; Methods; Monitor; Morbidity - disease rate; National Institute of Diabetes and Digestive and Kidney Diseases; Nephrotic Syndrome; Participant; Patients; Pharmaceutical Preparations; Pneumococcal Infections; Pneumococcal vaccine; Population; Preparation; Prevention Measures; Prevention strategy; Preventive measure; Prospective, cohort study; Proteinuria; Rare Diseases; Recommendation; Regimen; Renal function; Renal glomerular disease; Research; Research Design; Resources; Risk Factors; Sample Size; Scientist; Statistical Methods; Streptococcus pneumoniae; Testing; Time; Training; Vaccinated; Vaccination; Vaccines; Work; career; career development; clinical practice; cohort; cost effective; epidemiology study; experience; health care service utilization; high risk; high risk population; hospital care; immunogenicity; in vivo; influenza infection; influenza virus vaccine; longitudinal analysis; longitudinal dataset; mortality; patient population; pragmatic trial; prophylactic; prospective; seroconversion; urinary; vaccination strategy; vaccine effectiveness; vaccine immunogenicity; vaccine response

ABSTRACT Influenza and pneumococcal infections occurring in individuals with glomerular disease are preventable contributors to excess healthcare utilization, morbidity, and mortality, and occur at a rate approximately 30 times higher among individuals with glomerular diseases compared to the general US population. Vaccination is a powerful and cost-effective method to reduce infectious burden, however, vaccine immunogenicity and effectiveness have not been adequately studied in this high-risk patient population. Vaccination may not yield protective or sustained immune responses in individuals with glomerular disease as a result of exposure to immunosuppressive medications, altered immune cell function, and urinary loss of immunoglobulin and complement factors. As a result, there remain pressing questions regarding whether these antibodies confer in- vivo protection from influenza and pneumococcal infection. Evidence gaps that need to be addressed in preparation for pragmatic trials focused on infection-prevention measures in this population include frequency of administration of recommended vaccines, pervasiveness of infectious complications, and rates of influenza and pneumococcal vaccine seroconversion and seroprotection. Prior studies have been limited by small sample size, insufficiently characterized cohorts, and the use of assays that measure non-opsonic, and thus potentially non- functional, antibodies. The objective of this proposal is to describe the association of influenza and pneumococcal vaccination with influenza and pneumococcal infections and describe functional vaccine immunogenicity in patients with glomerular disease. Three projects have been proposed to achieve this objective: an analysis of influenza and pneumococcal vaccine use and effectiveness in a nationwide healthcare claims database (MarketScan®), a study examining vaccine immunogenicity in the multicenter NIDDK-sponsored Cure Glomerulonephropathy (CureGN) study, and creation of a multicenter cohort to examine 23-valent pneumococcal vaccine immunogenicity in children with nephrotic syndrome. The primary hypothesis is that, independent of kidney function, rates of influenza and pneumococcal infection and suboptimal vaccine response will be higher in individuals with active glomerular disease, greater immunosuppression exposure, greater proteinuria, and younger age. Dr. Glenn’s career development goals include gaining advanced training in statistical methods and epidemiologic study design, with a focus on the analysis of longitudinal datasets, healthcare claims data, and multicenter vaccine immunogenicity studies. Dr. Glenn will receive mentorship from Dr. Amy Mottl and Dr. Ronald Falk, both experts in the field of glomerular kidney disease. Additionally, Dr. Glenn will have a scientific advisory committee comprised of experts in vaccine immunogenicity, infectious disease, healthcare claims data analysis, and epidemiology. This work will inform the development of an R01 application in which Dr. Glenn leads a pragmatic trial investigating pneumococcal vaccination strategies among children with nephrotic syndrome.

抽象的 肾小球疾病患者发生的流感和肺炎球菌感染是可以预防的 造成医疗保健过度利用、发病率和死亡率的因素，发生率约为 30 倍 与美国普通人群相比，肾小球疾病患者的患病率更高。疫苗接种是一个 减少感染负担的有效且具有成本效益的方法，但是疫苗的免疫原性和 尚未在这一高危患者群体中充分研究其有效性。疫苗接种可能无效 由于暴露于肾小球疾病而导致的个体的保护性或持续性免疫反应 免疫抑制药物、免疫细胞功能改变以及尿液中免疫球蛋白和免疫球蛋白的丢失 补充因素。因此，关于这些抗体是否具有以下作用仍然存在紧迫的问题： 体内保护免受流感和肺炎球菌感染。需要解决的证据差距 准备针对该人群的感染预防措施的务实试验，包括频率 推荐疫苗的接种、感染并发症的普遍性以及流感和流感的发生率 肺炎球菌疫苗血清转化和血清保护。先前的研究受到样本量较小的限制， 没有充分表征的队列，以及使用测量非调理性的测定法，因此可能是非 功能性, 抗体. 该提案的目的是描述流感和肺炎球菌疫苗接种与 流感和肺炎球菌感染并描述了患者的功能性疫苗免疫原性 肾小球疾病。已提出三个项目来实现这一目标：对流感和流感病毒的分析 全国医疗保健索赔数据库 (MarketScan®) 中的肺炎球菌疫苗使用情况和有效性 NIDDK 资助的多中心治愈肾小球肾病疫苗免疫原性研究 (CureGN) 研究，并创建多中心队列来检查 23 价肺炎球菌疫苗 肾病综合征儿童的免疫原性。主要假设是，独立于肾脏 功能、流感和肺炎球菌感染率以及疫苗反应欠佳的情况会更高 患有活动性肾小球疾病、更多的免疫抑制暴露、更多的蛋白尿和 年龄较小。格伦博士的职业发展目标包括获得统计方法和 流行病学研究设计，重点是纵向数据集、医疗保健索赔数据和 多中心疫苗免疫原性研究。格伦博士将接受艾米·莫特尔博士和罗纳德博士的指导 法尔克是肾小球肾病领域的专家。此外，格伦博士还将提供科学咨询 委员会由疫苗免疫原性、传染病、医疗保健索赔数据分析专家组成， 和流行病学。这项工作将为格伦博士领导的 R01 应用程序的开发提供信息 调查肾病综合征儿童肺炎球菌疫苗接种策略的实用试验。