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

同种异体肺移植受者中高剂量与标准剂量流感疫苗的比较

• 批准号: 10405753
• 负责人: NATASHA Bassam HALASA
• 金额: $ 91.34万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-02-18 至 2027-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10405753
• 关键词: 16 year old; Academic Medical Centers; Ache; Acute; Address; Adult; Adverse event; Alabama; Allografting; Antibodies; Antibody titer measurement; Antigens; B-Lymphocyte Subsets; B-Lymphocytes; Biopsy; CD4 Positive T Lymphocytes; Cellular Assay; Chronic; Clinical; Cytometry; Development; Disease; Dose; Double-Blind Method; Enrollment; Environmental Exposure; Evaluation; Fatigue; Fever; Frequencies; Functional disorder; HLA Antigens; Headache; Hemagglutination; Immune response; Immunologics; Immunosuppression; Individual; Induration; Influenza; Influenza A virus; Influenza B Virus; Influenza vaccination; Injections; Knowledge; Lung Transplantation; Malaise; Measurement; Measures; Morbidity - disease rate; Myalgia; Nausea; Organ Transplantation; Pain; Patients; Phase; Phenotype; Population; Prevention strategy; Publishing; Randomized; Reaction; Recommendation; Redness; Regimen; Reporting; Respiratory Failure; Risk; Safety; Seasons; Serious Adverse Event; Severities; Site; Solid; Swelling; T-Cell Activation; T-Lymphocyte; Testing; Transplant Recipients; Universities; Vaccination; Vaccine Antigen; Vaccines; Vomiting; Washington; comorbidity; exhaustion; high risk; immunogenic; immunogenicity; immunosuppressed; improved; influenza virus vaccine; influenzavirus; lung allograft; organ transplant recipient; pathogen; phase II trial; post-transplant; preservation; response; senescence; seroconversion; side effect; transplant centers; trial comparing; vaccination strategy; vaccine immunogenicity; vaccine strategy; vaccine trial

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.

项目概要 流感病毒是实体器官移植（SOT）受者（包括同种异体肺移植物）的重要病原体 收件人。此外，与其他SOT相比，同种异体肺移植受者患有更严重的流感疾病。 然而，由于必要的免疫抑制，这些人对标准剂量 (SD) 的反应较差 灭活流感疫苗（IIV）。最近的研究调查了两种克服免疫不良的策略 SOT 接受者的反应：(1) 与 SD-IIV 相比，给予高剂量 (HD)-IIV 和 (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 接受者报告 HD-IIV 安全且更具免疫原性；然而，移植后的中位时间 是38个月。第二项研究是针对成年 SOT 接受者的另一项 II 期试验，移植后中位数 为期 18 个月的研究报告称，间隔 1 个月施用的两剂 SD-IIV 具有更强的免疫原性 比一剂 SD-IIV 更有效。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时。此外，这些研究仅限于肺 移植受者是最容易患流感相关合并症（包括呼吸道疾病）的人群 衰竭、急性细胞排斥和慢性肺同种异体移植功能障碍。最后，分两剂服用 此前尚未在 SOT 接受者中评估同一流感季节 HD-IIV 的情况。因此，最优的 同种异体肺移植受者在移植后早期的免疫策略仍不清楚。在 此外，同种异体肺移植物中流感疫苗免疫原性的免疫预测因子和相关性 接收者尚未明确界定。我们提案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 四价的受者 灭活流感疫苗 (QIV) 将对流感具有更高的 HAI 几何平均滴度 (GMT) 与接受两剂 SD-QIV 的患者相比。为了检验这一假设并解决 鉴于上述关键知识差距，我们建议进行 II 期、多中心、随机对照研究 比较一个月内施用的两剂 HD-QIV 和两剂 SD-QIV 的免疫原性和安全性试验 移植后≥16岁零1-35个月的肺同种异体移植受者除外。这项研究将 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、阿拉巴马大学伯明翰分校和华盛顿大学。结果 这项研究将阐明成人肺同种异体移植受者的免疫反应并帮助指导疫苗接种 移植后早期的建议。此外，我们的研究结果可能有助于指导最佳 其他免疫抑制人群的疫苗策略。