High vs. Standard Dose Flu Vaccine in Adult Stem Cell Transplant Recipients

成人干细胞移植受者的高剂量流感疫苗与标准剂量流感疫苗

• 批准号: 9352550
• 负责人: NATASHA Bassam HALASA
• 金额: $ 83.27万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-05 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9352550
• 关键词: 18 year old; Academic Medical Centers; Ache; Adult; Adverse event; Age-Years; Alabama; Allogenic; Antibody Response; Antigens; B-Lymphocytes; Biological Assay; CD19 gene; CD8B1 gene; Cell Count; Cells; Complete Blood Count; Cytometry; Data; Dose; Electronic Mail; Enrollment; Event; Fatigue; Fever; Flow Cytometry; Follow-Up Studies; Formulation; Fred Hutchinson Cancer Research Center; Frequencies; Headache; Hemagglutination; Hematopoietic Stem Cell Transplantation; Immune response; Immunocompromised Host; Immunoglobulin G; Immunoglobulin M; In Vitro; Individual; Induration; Influenza; Influenza A virus; Influenza B Virus; Influenza vaccination; Injection of therapeutic agent; Knowledge; Lead; Licensure; Malaise; Measures; Methods; Myalgia; Nausea; Pain; Patients; Persons; Phase; Phenotype; Plasmablast; Population; Probability; Randomized; Recommendation; Redness; Safety; Serum; Severities; Site; Swelling; T cell response; T-Lymphocyte; Technology; Telephone; Time; Transplant Recipients; Transplantation; Universities; Vaccination; Vaccine Antigen; Vaccines; Viral Antigens; Vomiting; Vulnerable Populations; adult stem cell; clinical research site; cohort; immunogenic; immunogenicity; in vivo; influenza virus vaccine; influenzavirus; medical schools; next generation; pathogen; patient population; response; safety study; standard measure; trial comparing; vaccine response

PROJECT SUMMARY Influenza virus is a serious pathogen in immunocompromised persons, especially hematopoietic stem cell transplant (HSCT) recipients. However, these individuals respond poorly to trivalent inactivated influenza vaccine (TIV). High dose (HD)-TIV has increased immunogenicity and efficacy in adults >65 years of age. It is not known whether a HD-TIV will be safe and immunogenic in severely immunocompromised persons. The standard measure of immunogenicity for TIV is hemagglutination inhibition (HAI) titers. The central hypothesis of our proposal is that HD-TIV will be more immunogenic compared to standard dose quadrivalent inactivated influenza vaccine (QIV) in adult HSCT recipients as evident by higher HAI antibody responses to influenza A antigens. The proposed study is a multi-center, phase II immunogenicity and safety trial comparing two doses of HD-TIV to standard dose QIV in adult HSCT recipients. A total of 138 patients (≥18 years of age) who received an allogeneic HSCT and are 3-23 months post-transplant will be enrolled at the following clinical sites: Vanderbilt University Medical Center (lead site); Northwestern University Feinberg School of Medicine, Fred Hutchinson Cancer Research Center; University of Alabama at Birmingham School of Medicine. The specific aims are as follow: Specific Aim 1) to determine whether HD-TIV compared with standard dose QIV will increase the probability of achieving either a ≥4-fold rise in HAI titer, a HAI titer ≥1:40, or a higher geometric mean titer (GMT) to influenza A antigens in adult HSCT recipients; Specific Aim 2) to determine the frequency and severity of solicited local injection site adverse events and solicited systemic adverse events associated with HD-TIV compared with standard dose QIV in adult HSCT recipients; Specific Aim 3) to define the relationship between HAI titers, in vivo T and B cell phenotype, and in vitro influenza-specific T and B cell responses in adult HSCT recipients receiving either HD-TIV or standard dose QIV. Subjects will be randomized in a 1:1 fashion to receive either 2 doses of 2017-2018 HD-TIV (60µg of each influenza antigen) or 2 doses of standard dose QIV (15µg of each influenza antigen). HAI and microneutralization titers to influenza virus antigens, phenotypic B and T cell responses, B and T cell specific influenza responses, complete blood count, quantitative CD4+/CD8+/CD19+ levels, and quantitative serum IgG and IgM concentrations will be measured prior to the first and second vaccine dose, 28-42 days after the second vaccine dose, and approximately 7 months after second vaccine. Solicited adverse events will be recorded by the subject seven days following vaccination and a telephone/email follow-up by study staff. The results of this study will fill a gap in knowledge regarding influenza vaccine responses in HSCT recipients and will guide vaccine recommendations in this vulnerable population.

项目摘要 流感病毒是免疫功能低下者，尤其是造血干细胞缺乏者的重要病原体 移植（HSCT）受者。然而，这些个体对三价灭活流感的反应较差 TIV疫苗。高剂量（HD）-TIV在>65岁的成人中具有增加的免疫原性和功效。是 尚不清楚HD-TIV在严重免疫功能低下的人群中是否安全和具有免疫原性。的 TIV免疫原性标准量度是血凝抑制（HAI）滴度。核心假设 我们的建议是，与标准剂量四价灭活相比，HD-TIV的免疫原性更强 流感疫苗（QIV）在成人HSCT接受者中的作用，如对甲型流感的较高HAI抗体应答所证实 抗原拟议的研究是一项比较两种剂量的多中心、II期免疫原性和安全性试验 HD-TIV与标准剂量QIV相比的差异。共138例患者（≥18岁）， 接受同种异体HSCT且移植后3-23个月的受试者将在以下临床研究中心入组： 范德比尔特大学医学中心（牵头单位）;西北大学范伯格医学院，弗雷德 哈钦森癌症研究中心;亚拉巴马大学伯明翰医学院。具体 目的如下：具体目的1）确定HD-TIV与标准剂量QIV相比是否 增加实现HAI滴度升高≥4倍、HAI滴度≥1：40或更高的可能性 成人HSCT受者中甲型流感抗原的几何平均滴度（GMT）;特异性目标2） 确定征集性局部注射部位不良事件的频率和严重程度， 成人HSCT中HD-TIV与标准剂量QIV相比相关的全身不良事件 受体;具体目的3）确定HAI滴度、体内T和B细胞表型之间的关系， 以及接受HD-TIV或HD-TIV的成人HSCT受者的体外流感特异性T和B细胞应答 或标准剂量QIV。受试者将以1：1的比例随机接受2剂2017-2018 HD-TIV（每种流感抗原60微克）或2剂标准剂量QIV（每种流感抗原15微克）。 HAI和对流感病毒抗原的微量中和滴度、表型B和T细胞应答、B和T细胞 特异性流感反应、全血细胞计数、定量CD 4 +/CD 8 +/CD 19+水平和定量 将在第一次和第二次疫苗接种前28-42天测量血清IgG和IgM浓度 第二次接种疫苗后，以及第二次接种疫苗后约7个月。征集性不良事件将 由受试者在疫苗接种后7天记录，并由研究工作人员进行电话/电子邮件随访。 这项研究的结果将填补有关HSCT受者流感疫苗应答的知识空白 并将指导这一脆弱人群的疫苗推荐。