Comparison of High Dose vs. Standard Dose Influenza Vaccines in Lung Allograft Recipients

项目总结 流感病毒是实体器官移植(SOT)受者的重要病原体，包括肺移植 收件人。此外，与其他SOT相比，肺移植受者患有更严重的流感疾病。 然而，由于必需的免疫抑制，这些人对标准剂量(SD)的反应很差。 流感灭活疫苗(IIV)。最近的研究调查了两种克服免疫力低下的策略。 SOT受者的反应：(1)大剂量(HD)-IIV与SD-IIV的比较；(2)两剂 SD-IIV与同一流感季节的一剂SD-IIV进行比较。第一项研究是在成人SOT中进行的 受者报告说，HD-IIV是安全的，更具免疫原性；然而，移植后中位数 是38个月。第二项研究是另一项针对成年SOT受者的II期试验，移植后中位数为 一项为期18个月的研究报告称，间隔一个月注射两剂SD-IIV更具免疫力 而不是一剂SD-IIV。虽然这些研究很有希望，但缺乏对移植后早期的评估， 当SOT患者最容易感染流感的时候。此外，这些研究对肺的包含性有限。 移植受者，这一人群患流感相关共病的风险最高，包括呼吸道疾病 衰竭、急性细胞排斥反应和慢性同种异体肺移植功能障碍。最后，给药两剂 同一流感季节的HD-IIV感染情况以前从未在接受SOT治疗的患者中进行过评估。因此，最优的 同种异体肺移植受者移植后早期的免疫策略尚不清楚。在……里面 此外，流感疫苗在肺移植中免疫原性的免疫学预测因子和相关因素 收件人尚未得到很好的定义。我们建议的中心假设是同种异体肺移植 移植后1-35个月并接受两剂HD-四价注射的受者 流感灭活疫苗(QIV)对流感的HAI几何平均滴度(GMT)将更高 将这些抗原与接受两剂SD-QIV的人进行比较。要检验这一假设并解决 对于上述关键知识缺口，我们建议进行第二阶段、多中心、随机对照 两剂HD-QIV与两剂SD-QIV一个月免疫原性及安全性比较 在肺移植受者中除外，他们在移植后16年1-35个月≥。这项研究将是 在五个肺移植中心进行-范德比尔特大学医学中心，杜克大学， 西北大学、伯明翰阿拉巴马大学和华盛顿大学。结果是 这项研究将阐明成人肺移植受者的免疫反应，并有助于指导疫苗接种。 移植后早期的建议。此外，我们的发现可能有助于指导最优 其他免疫抑制人群的疫苗策略。

PROJECT SUMMARY Influenza virus is a significant pathogen in solid organ transplant (SOT) recipients, including lung allograft recipients. Moreover, compared to other SOT, lung allograft recipients have more severe influenza disease. However, due to requisite immunosuppression, 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, conducted in adult SOT recipients, reported that HD-IIV was safe and more immunogenic; however, the median post-transplant period was 38 months. The second study, another phase II trial in adult SOT recipients with a median post-transplant period of 18 months, reported that two doses of SD-IIV administered one month apart was more immunogenic than one-dose of SD-IIV. While promising, these studies lack evaluation in the early post-transplant period, when SOT patients are most vulnerable to influenza. Moreover, these studies had limited inclusion of lung transplant recipients, a population that is most at risk for influenza-related comorbidities, including respiratory failure, acute cellular rejection, and chronic lung allograft dysfunction. Finally, the administration of two doses of HD-IIV in the same influenza season has not previously been evaluated in SOT recipients. Thus, the optimal immunization strategy for lung allograft recipients in the early post-transplant period remains unknown. In addition, the immunologic predictors and correlates of influenza vaccine immunogenicity in lung allograft recipients have not been well-defined. The central hypothesis of our proposal is that lung allograft recipients who are 1-35 months post-transplant and receiving two doses of HD-quadrivalent inactivated influenza vaccine (QIV) will have higher HAI geometric mean titers (GMTs) to influenza antigens compared to those 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 HD-QIV to two doses SD-QIV administered one month apart in lung allograft recipients who are ≥16 years and 1-35 months post-transplant. This study will be conducted at five lung transplant centers—Vanderbilt University Medical Center, Duke University, Northwestern University, University of Alabama in Birmingham, and University of Washington. The results of this study will illuminate immune responses in adult lung allograft recipients and help guide vaccine recommendations during the early post-transplant period. Moreover, our findings may help guide optimal vaccine strategies in other immunosuppressed populations.