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: 10017602
• 负责人: NATASHA Bassam HALASA
• 金额: $ 86.28万
• 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/10017602
• 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; Immunization; Immunocompromised Host; Immunologics; Immunosuppression; Impairment; Individual; Induration; Influenza; Influenza A Virus, H1N1 Subtype; Influenza A virus; Injections; Kidney; Knowledge; Lead; 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; pathogen; phase II trial; post-transplant; primary endpoint; response; secondary endpoint; senescence; seroconversion; standard measure; trial comparing; vaccination strategy; vaccine response

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.

项目摘要 流感病毒是成年实体器官移植受者的重要病原体。但这些 个体对标准剂量（SD）灭活流感疫苗（IIV）的应答较差。最近的研究 研究了两种策略来克服SOT接受者中的不良免疫应答：（1）施用高浓度的 剂量（HD）-IIV与SD-IIV相比，以及（2）两个剂量的SD-IIV与一个剂量的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，并报告了更高的免疫原性;然而，移植后的中位时间为38个月。在 另一项针对成年SOT接受者的II期试验，与一剂SD-1相比，一个月间隔两剂SD-1 IV。 IIV显示免疫原性增加，移植后中位时间为18个月。因此这些 研究缺乏对这一脆弱人群移植后早期的评估。另夕h 在相同的流感季节中施用两剂HD-IIV尚未在SOT接受者中进行评估。 因此，移植后不到12个月的SOT受体的最佳免疫策略是未知的。在 此外，SOT接种者中流感疫苗免疫原性的免疫学预测因子和相关因素 还没有很好的定义。我们建议的中心假设是，成年SOT接受者是 1-11从移植开始几个月，并接受两剂HD-IIV将有更高的 与成人相比，甲型流感抗原的血凝抑制几何平均滴度（GMT） 在一个流感季节接受两剂SD-IIV的SOT接受者。为了验证这一假设， 解决上述关键知识差距，我们建议进行第二阶段，多中心， 随机对照免疫原性和安全性试验，比较单剂HD-IIV、两剂SD- 移植后1-11个月，在成人肾脏、心脏和/或肝脏SOT接受者中接受两剂HD-IIV或两剂HD-IIV。的 这项研究的结果将解决有关流感疫苗战略的重大知识差距， 成人SOT接受者的免疫反应，并将指导疫苗的建议，在早期后， 移植期