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

项目总结 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 个人对标准剂量(SD)灭活流感疫苗(IIV)的反应很差。最近的研究表明 研究了克服SOT受者免疫反应不良的两种策略：(1)给予高剂量的 剂量(HD)-IIV与SD-IIV的比较和(2)两剂SD-IIV与相同剂量的SD-IIV的比较 流感季节。第一项研究比较了成年SOT受者的HD-IIV和SD-IIV，并指出HD-IIV 是安全的，据报道有较高的免疫原性；然而，移植后的中位数为38个月。在……里面 另一项针对成年SOT接受者的II期试验，每月间隔两剂SD-IIV，而不是一剂SD-IIV。 IVV显示免疫原性增强，移植后中位数为18个月。因此，这些 在这一弱势群体中，研究缺乏对移植后早期阶段的评估。此外， 在同一流感季节注射两剂HD-IIV尚未在接受SOT治疗的患者中进行评估。 因此，移植后不到12个月的SOT受者的最佳免疫策略是未知的。在……里面 此外，SOT受者流感疫苗免疫原性的免疫学预测因素和相关因素 还没有得到明确的定义。我们建议的中心假设是，成年SOT接受者 移植后1-11个月接受两剂HD-IIV的患者将有更高的 甲型流感抗原血凝抑制几何平均滴度(GMT)与成人的比较 在一个流感季节接受两剂SD-IIV的SOT接受者。为了检验这一假说， 为了解决上述关键知识差距，我们提议进行第二阶段、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，成人肾、心脏和/或肝脏SOT受者接受静脉注射或两剂HD-IIV。这个 这项研究的结果将解决关于流感疫苗策略和 成人SOT受者的免疫反应，并将指导早期的疫苗推荐 移植时期。

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.