Comparison of High vs. Standard Dose Influenza Vaccine in Pediatric Solid Organ Transplant Recipients

项目总结 流感病毒是儿童实体器官移植(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。一项研究比较了成年SOT受者的HD-IIV和SD-IIV，并指出HD-IIV是 安全性和更强的免疫原性；然而，移植后的中位数为38个月。一期儿科 比较单剂HD-IIV和SD-IIV的研究是安全的，具有更高的免疫原性，但这项研究 受样本量小和移植后接种疫苗的中位数为26个月的限制。在另一个国家 成人SOT受者的II期试验，两剂SD-IIV相隔一个月与一剂SD-IIV比较 在移植后18个月的中位数给药时，显示免疫原性略有增加。因此， 这些研究既缺乏对移植后早期的评估，也缺乏对大量儿科人群的评估。 此外，在同一流感季节注射两剂HD-IIV还没有在#年进行评估。 儿童SOT接受者。因此，24岁以下儿童SOT受者的最佳免疫策略 移植后几个月的情况还不得而知。此外，流感疫苗的免疫学预测因素和相关因素 儿童SOT受者的免疫原性尚未得到很好的定义。我们的核心假设是 建议移植后1-23个月的儿童SOT受者接受两剂HD- 四价灭活流感疫苗(QIV)将具有类似的安全性，但HAI几何平均值更高 流感抗原效价(GMT)与接受两剂SD-SOT的儿童SOT受者的比较 QIV.为了验证这一假设并解决上述关键知识差距，我们建议进行一项 II期多中心随机对照免疫原性和安全性试验 两种剂量的SD-QIV在接受SOT的儿童肾、心脏和/或肝脏移植后1-23个月。这个 这项研究的结果将解决关于流感疫苗策略和 儿童SOT受者的免疫反应，并将指导早期疫苗推荐 移植时期。

PROJECT SUMMARY Influenza virus is a significant pathogen in pediatric 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. One study compared HD-IIV vs. SD-IIV in adult SOT recipients and noted that HD-IIV was safe and more immunogenic; however, the median post-transplant period was 38 months. A phase I pediatric study comparing a single dose of HD-IIV vs. SD-IIV was safe with higher immunogenicity, but the study was limited by small sample size and median post-transplant vaccine administration was 26 months. In another phase II trial of adult SOT recipients, two doses of SD-IIV one month apart compared to one-dose of SD-IIV revealed modestly increased immunogenicity when given at a median of 18 months post-transplant. Therefore, these studies lack both evaluation in the early post-transplant period and substantive pediatric populations. Additionally, the administration of two-doses of HD-IIV in the same influenza season has not been evaluated in pediatric SOT recipients. Thus, the optimal immunization strategy for pediatric SOT recipients less than 24 months post-transplant is unknown. In addition, immunologic predictors and correlates of influenza vaccine immunogenicity in pediatric SOT recipients have not been well-defined. The central hypothesis of our proposal is that pediatric SOT recipients 1-23 months post-transplant who receive two doses of HD- quadrivalent inactivated influenza vaccine (QIV) will have similar safety but higher HAI geometric mean titers (GMTs) to influenza antigens compared to pediatric SOT recipients receiving two doses of SD- QIV. 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 two doses of HD-QIV to two doses of SD-QIV in pediatric kidney, heart, and/or liver SOT recipients 1-23 months post-transplant. The results of this study will address significant knowledge gaps regarding influenza vaccine strategies and immune responses in pediatric SOT recipients and will guide vaccine recommendations in the early post- transplant period.