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: 10445593
• 负责人: Dorey Glenn
• 金额: $ 20.18万
• 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/10445593
• 关键词: Address; Adult; Advisory Committees; Age; Antibodies; Antibody titer measurement; Attenuated; Biological Assay; Biopsy; Caring; Cause of Death; Cell physiology; Characteristics; Child; Clinical; Communicable Diseases; Complement; Data; Data Analyses; Databases; Development; Disease; Epidemiology; Exposure to; Foundations; Frequencies; Goals; Guidelines; Healthcare; Hospitals; 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; Regimen; Renal function; Renal glomerular disease; Research; Research Design; Research Training; Resources; Risk Factors; Sample Size; Scientist; Statistical Methods; Streptococcus pneumoniae; Testing; Time; Training; Use Effectiveness; Vaccinated; Vaccination; Vaccines; Work; career; career development; clinical practice; cohort; cost effective; epidemiology study; experience; health care service utilization; high risk; high risk population; 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.

摘要 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 导致过度医疗利用、发病率和死亡率，发生率约为 与美国普通人群相比，肾小球疾病患者的发病率更高。接种疫苗是一种 但是，疫苗免疫原性和 在这一高风险患者人群中的有效性尚未得到充分研究。接种疫苗可能不会产生 肾小球疾病患者由于暴露于以下物质而产生的保护性或持续性免疫应答 免疫抑制药物、免疫细胞功能改变和免疫球蛋白尿丢失， 补充因素。因此，仍然存在紧迫的问题，这些抗体是否赋予- 对流感和肺炎球菌感染的体内保护。需要解决的证据差距 在这一人群中开展注重感染预防措施的实用试验的准备工作包括： 推荐疫苗的接种、感染性并发症的普遍性以及流感和 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小的限制， 不充分表征的群组，以及使用测量非调理素的测定，因此可能是非调理素的。 功能性抗体。 本提案的目的是描述流感和肺炎球菌疫苗接种与 并描述了功能性疫苗免疫原性 肾小球疾病为实现这一目标，提出了三个项目：流感分析和 肺炎球菌疫苗的使用和有效性在全国范围内的医疗索赔数据库（MarketScan®）， 在NIDDK赞助的多中心治疗肾小球肾病中检查疫苗免疫原性的研究 （CureGN）研究，并建立一个多中心队列来检查23价肺炎球菌疫苗 肾病综合征患儿免疫原性研究主要假设是，独立于肾脏 功能，流感和肺炎球菌感染率和次优疫苗反应将更高， 患有活动性肾小球疾病、免疫抑制剂暴露量更大、蛋白尿更多的个体， 更年轻。Glenn博士的职业发展目标包括获得统计方法方面的高级培训， 流行病学研究设计，重点分析纵向数据集、医疗索赔数据和 多中心疫苗免疫原性研究。Glenn博士将接受Amy Mottl博士和罗纳德博士的指导 福尔克，两位都是肾小球肾病领域的专家。另外，格伦博士将有一个科学顾问 委员会由疫苗免疫原性、传染病、医疗索赔数据分析方面的专家组成， 和流行病学。这项工作将告知R 01应用程序的开发，其中Glenn博士领导了一个 肾病综合征儿童肺炎球菌疫苗接种策略的实用性试验