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.

项目摘要 流感病毒是实体器官移植（SOT）受者（包括肺移植）的重要病原体 受惠人士此外，与其他SOT相比，肺移植受者有更严重的流感疾病。 然而，由于必需的免疫抑制，这些个体对标准剂量（SD）的反应很差。 灭活流感疫苗（IIV）。最近的研究调查了两种策略，以克服免疫不良 SOT接受者的反应：（1）与SD-IIV相比，给予高剂量（HD）-IIV，和（2）两个剂量的 SD-IIV与同一流感季节的一剂SD-IIV相比。第一项研究在成人SOT中进行， 接受者报告HD-IIV是安全的，免疫原性更强;然而，移植后的中位时间 是38个月。第二项研究是另一项在成人SOT受者中进行的II期试验， 18个月期间，报告称间隔一个月给予两剂SD-IIV的免疫原性更强 比一剂SD-IIV更有效虽然这些研究很有希望，但缺乏移植后早期的评估， SOT患者最容易感染流感。此外，这些研究对肺的纳入有限。 移植受者是流感相关合并症风险最高的人群，包括呼吸道疾病。 衰竭、急性细胞排斥和慢性肺同种异体移植物功能障碍。最后，给药两剂 HD-IIV在同一流感季节的发病率以前没有在SOT接受者中进行过评估。因此， 肺移植受者在移植后早期的免疫策略仍然未知。在 此外，流感疫苗免疫原性在肺移植物中的免疫学预测因子和相关性 没有明确界定接受者。我们建议的中心假设是， 移植后1-35个月并接受两剂HD四价疫苗的受者 灭活流感疫苗（QIV）对流感病毒的HAI几何平均滴度（GMT）更高 与接受两剂SD-QIV的患者相比，为了验证这一假设， 鉴于上文概述的关键知识差距，我们建议进行第二阶段、多中心、随机对照 比较两种剂量HD-QIV与两种剂量SD-QIV给药一个月的免疫原性和安全性试验 除肺移植受者≥16岁和移植后1-35个月外。本研究将 在五个肺移植中心-范德比尔特大学医学中心，杜克大学， 西北大学、伯明翰的亚拉巴马大学和华盛顿大学。的结果 这项研究将阐明成人肺移植受者的免疫反应， 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的 其他免疫抑制人群的疫苗策略。