Comparison of High vs. Standard Dose Influenza Vaccines in Adult Solid Organ Transplant Recipients

成人实体器官移植受者中高剂量与标准剂量流感疫苗的比较

• 批准号: 10661582
• 负责人: NATASHA Bassam HALASA
• 金额: $ 81.43万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10661582
• 关键词: Ache; Address; Adult; Adverse event; Alabama; Antigens; B-Lymphocyte Subsets; B-Lymphocytes; CD4 Positive T Lymphocytes; Cellular Assay; Cytometry; Disease; Dose; Enrollment; Evaluation; Event; Fatigue; Fever; Frequencies; Headache; Heart; Hemagglutination; Immune; Immune response; Immunocompromised Host; Immunologics; Immunophenotyping; Immunosuppression; Impairment; Individual; Induration; Influenza; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H3N2 Subtype; Influenza A virus; Injections; Kidney; Knowledge; Lead; Licensing; Liver; Malaise; Measures; Medical center; Myalgia; Nausea; Organ Transplantation; Pain; Phase; Phenotype; Placebos; Population; Prevention strategy; Randomized; Recommendation; Redness; Reporting; Safety; Seasons; Severities; Site; Solid; Swelling; T-Lymphocyte; Testing; Time; Transplant Recipients; Transplantation; Universities; Vaccination; Vaccines; Vomiting; Vulnerable Populations; Washington; exhaustion; high risk; immune activation; immunogenicity; influenza virus vaccine; influenzavirus; medical schools; organ transplant recipient; pathogen; phase II trial; post-transplant; primary endpoint; response; seasonal influenza; secondary endpoint; senescence; seroconversion; standard measure; trial comparing; vaccination strategy; vaccine immunogenicity; vaccine response; vaccine strategy

PROJECT SUMMARY Influenza virus is a significant pathogen in adult solid organ transplant (SOT) recipients. However, these individuals respond poorly to standard-dose (SD) inactivated influenza vaccine (IIV). Recent studies have investigated two strategies to overcome poor immune responses in SOT recipients: (1) administration of high- dose (HD)-IIV compared to SD-IIV and (2) two doses of SD-IIV compared to one dose of SD-IIV in the same influenza season. The first study compared HD-IIV vs.SD-IIV in adult SOT recipients and noted that HD-IIV was safe and reported higher immunogenicity; however, the median post-transplant period was 38 months. In another phase II trial of adult SOT recipients, two doses of SD-IIV a month apart compared to one-dose of SD- IIV revealed increased immunogenicity, with a median post-transplant period of 18 months. Therefore, these studies lack evaluation in the early post-transplant period in this vulnerable population. Additionally, the administration of two-doses of HD-IIV in the same influenza season has not been evaluated in SOT recipients. Thus, the optimal immunization strategy for SOT recipients less than 12 months post-transplant is unknown. In addition, the immunologic predictors and correlates of influenza vaccine immunogenicity in SOT recipients have not been well-defined. The central hypothesis of our proposal is that adult SOT recipients that are 1-11 months out from transplant and are receiving two doses of HD-IIV will have higher hemagglutination inhibition geometric mean titers (GMT) to influenza A antigens compared to adult SOT recipients receiving two doses of SD-IIV over one influenza season. To test this hypothesis and address the critical knowledge gaps outlined above, we propose to conduct a phase II, multi-center, randomized-controlled immunogenicity and safety trial comparing either one dose of HD-IIV, two doses of SD- IIV, or two doses of HD-IIV in adult kidney, heart, and/or liver SOT recipients 1-11 months post-transplant. The results of this study will address significant knowledge gaps regarding influenza vaccine strategies and immune responses in adult SOT recipients and will guide vaccine recommendations in the early post- transplant period.

项目概要 流感病毒是成人实体器官移植（SOT）受者的重要病原体。然而，这些 个体对标准剂量 (SD) 灭活流感疫苗 (IIV) 的反应较差。最近的研究有 研究了两种克服 SOT 接受者免疫反应不良的策略：(1) 给予高剂量 剂量 (HD)-IIV 与 SD-IIV 相比，以及 (2) 两剂 SD-IIV 与同一剂量中的一剂 SD-IIV 相比 流感季节。第一项研究在成人 SOT 接受者中比较了 HD-IIV 与 SD-IIV，并指出 HD-IIV 是安全的，并报告有更高的免疫原性；然而，移植后的中位时间为 38 个月。在 另一项对成人 SOT 接受者进行的 II 期试验，每月两次注射 SD-IIV 与注射一次 SD- IIV 显示免疫原性增加，移植后中位时间为 18 个月。因此，这些 研究缺乏对这一弱势群体移植后早期的评估。此外， 尚未在 SOT 接受者中评估在同一流感季节给予两剂 HD-IIV 的情况。 因此，移植后 12 个月内 SOT 受者的最佳免疫策略尚不清楚。在 此外，SOT 接受者中流感疫苗免疫原性的免疫预测因子和相关性 尚未被明确定义。我们提案的中心假设是，成年 SOT 接受者 移植后 1-11 个月并接受两剂 HD-IIV 的患者的死亡率会更高 与成人相比，甲型流感抗原的血凝抑制几何平均滴度 (GMT) SOT 接受者在一个流感季节接受两剂 SD-IIV。为了检验这个假设并 为了解决上述关键知识差距，我们建议开展第二阶段、多中心、 随机对照免疫原性和安全性试验，比较一剂 HD-IIV、两剂 SD- 移植后 1-11 个月，成人肾脏、心脏和/或肝脏 SOT 接受者接受 IIV 或两剂 HD-IIV。这 这项研究的结果将解决有关流感疫苗策略和疫苗接种方面的重大知识差距 成人 SOT 接受者的免疫反应，并将指导后期早期的疫苗建议 移植期。