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

高剂量与标准剂量流感疫苗在儿科实体器官移植受者中的比较

• 批准号: 10621099
• 负责人: Lara A DANZIGER-ISAKOV
• 金额: $ 181.55万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-09 至 2028-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10621099
• 关键词: Ache; Acute; Address; Adult; Adverse event; Antibodies; Antibody titer measurement; Antigens; B-Lymphocyte Subsets; B-Lymphocytes; Biological Assay; Biopsy; CD4 Positive T Lymphocytes; Cellular Assay; Child; Childhood; Clinical; Cytometry; Data; Development; Dose; Double-Blind Method; Enrollment; Evaluation; Fatigue; Fever; Frequencies; HLA Antigens; Headache; Heart; Hemagglutination; Hospitalization; Immune; Immune response; Immunologics; Immunophenotyping; Impairment; Individual; Induration; Influenza; Influenza A virus; Influenza B Virus; Influenza vaccination; Injections; Kidney; Knowledge; Liver; Malaise; Measures; Myalgia; Nausea; Organ Transplantation; Pain; Phase; Phenotype; Population; Prevention strategy; Primary Prevention; Randomized; Reaction; Recommendation; Recording of previous events; Redness; Regimen; Safety; Sample Size; Seasons; Serum; Severities; Site; Solid; Swelling; T-Cell Activation; T-Lymphocyte; Testing; Vaccination; Vaccine Antigen; Vaccines; Vomiting; design; exhaustion; high risk; immune activation; immunogenic; immunogenicity; influenza infection; influenza virus vaccine; influenzavirus; organ transplant recipient; pathogen; phase 1 study; phase II trial; post-transplant; primary endpoint; response; seasonal influenza; senescence; standard measure; trial comparing; vaccination strategy; vaccine immunogenicity; vaccine strategy; vaccine trial

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.

项目摘要 流感病毒是小儿实体器官移植（SOT）受者的重要病原体。但这些 个体对标准剂量（SD）灭活流感疫苗（IIV）的应答较差。最近的研究 研究了两种策略来克服SOT接受者中的不良免疫应答：（1）施用高浓度的 剂量（HD）-IIV与SD-IIV相比，以及（2）两个剂量的SD-IIV与一个剂量的SD-IIV相比， 流感季节一项研究在成人SOT接受者中比较了HD-IIV与SD-IIV，并指出HD-IIV 安全且更具免疫原性;然而，移植后中位时间为38个月。一期儿科 比较HD-IIV与SD-IIV单次给药的研究是安全的，免疫原性更高，但该研究 受样本量小的限制，移植后疫苗接种的中位数为26个月。在另一 成人SOT接受者的II期试验，间隔一个月的两剂SD-IIV与一剂SD-IIV相比 显示在移植后18个月的中位数时给予适度增加的免疫原性。因此，我们认为， 这些研究既缺乏移植后早期的评估，也缺乏实质性的儿科人群。 此外，在同一流感季节给予两剂HD-IIV尚未进行评估， 儿科SOT接受者。因此，儿童SOT接受者的最佳免疫策略小于24 移植后的几个月是未知的。此外，流感疫苗的免疫学预测因子和相关因子 儿童SOT接受者的免疫原性尚未明确。我们的核心假设是 建议是，在移植后1-23个月接受两剂HD的儿科SOT接受者， 四价灭活流感疫苗（QIV）的安全性相似，但HAI几何平均值较高 与接受两剂SD的儿科SOT接受者相比， QIV.为了检验这一假设并解决上述关键知识差距，我们建议进行一次 一项比较两种剂量HD-QIV的II期、多中心、随机对照免疫原性和安全性试验 在移植后1-23个月，儿科肾脏、心脏和/或肝脏SOT接受者接受两次剂量的SD-QIV。的 这项研究的结果将解决有关流感疫苗战略的重大知识差距， 儿童SOT接受者的免疫反应，并将指导疫苗的建议，在早期后， 移植期