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

基本信息

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
项目类别：
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

项目摘要

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固体器官移植（SOT）受体中的重要病原体，包括肺同种异体移植物收件人。此外，与其他SOT相比，同种异体移植受体患有更严重的影响力。但是，由于必要的免疫抑制，这些人对标准剂量（SD）的反应不佳灭活的影响力疫苗（IIV）。最近的研究调查了克服不良免疫的两种策略 SOT接受者的响应：（1）与SD-IIV相比，高剂量（HD）-IIV给药，（2）两剂在同一影响力季节中，SD-IIV与一剂SD-IIV相比。第一项研究，在成人SOT中进行接受者报告说，HD-IIV是安全，更容易发生的。但是，移植后的中位数是38个月。第二项研究是成人SOT接受者的另一阶段试验，中位移植后中位数据报道，据报道，两次相隔一个月的SD-IIV剂量更为免疫原性比一剂SD-IIV。在承诺的同时，这些研究在移植后早期缺乏评估，当SOT患者最容易受到影响时。此外，这些研究的包括肺移植接受者，人口最有影响力相关的合并症的风险，包括呼吸系统衰竭，急性细胞排斥和慢性同种异体移植功能障碍。最后，给药两剂在SOT受体中，在同一影响力季节中的HD-IIV尚未评估。那，最佳在移植后早期，肺同种异体移植受体的免疫策略仍然未知。此外，肺合金中影响Za疫苗免疫原性的免疫学预测因子和相关性接收者没有明确定义。我们提案的中心假设是肺部分配移植后1-35个月的接受者接受两次HD Quadivalent 灭活的影响力疫苗（QIV）将具有较高的HAI几何均值（GMT）与接受两剂SD-QIV的抗原相比。检验这一假设并解决上面概述的批判知识差距，我们建议进行II期，多中心，随机控制免疫原性和安全试验将两剂HD-QIV与两剂SD-QIV进行比较一个月移植后≥16岁且1-35个月的肺同种异体接受者中。这项研究将是在五个肺移植中心举行西北大学，阿拉巴马大学伯明翰大学和华盛顿大学。结果这项研究将阐明成年肺同种异体接受者的免疫调查，并有助于引导疫苗在移植后期初期的建议。此外，我们的发现可能有助于指导最佳其他免疫抑制人群中的疫苗策略。