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的人，尤其是造血干细胞的严重病原体 移植（HSCT）受体。但是，这些人对三价灭活影响的反应较差 疫苗（TIV）。高剂量（HD）-TIV在成年人中的免疫原性和效率提高了65岁。这是 不知道在严重免疫功能低下的人中，HD-TIV是否会安全且免疫原性。这 TIV免疫原性的标准测量是血凝抑制（HAI）滴度。中心假设 我们的建议是，与标准剂量二次失活相比，HD-TIV将更具免疫原性 成年HSCT受体中的影响力疫苗（QIV）可以通过对影响力的较高的HAI抗体反应证明 抗原。拟议的研究是一项多中心的II期免疫原性和安全试验，比较了两剂 成人HSCT受体中标准剂量QIV的HD-TIV。共有138名患者（≥18岁） 收到同种异体HSCT，移植后3-23个月将在以下临床部位招收： 范德比尔特大学医学中心（领导地点）；弗雷德（Fred）西北大学费恩伯格医学院 哈钦森癌症研究中心；阿拉巴马大学伯明翰医学院。具体 目的如下：特定目的1）确定与标准剂量相比的HD-TIV是否会 增加HAI滴度上升≥4倍的可能性，HAI滴度≥1：40或更高的可能性 几何平均滴度（GMT）在成年HSCT受体中影响抗原；具体目标2） 确定固化的局部注射网站广告事件的频率和严重程度并巩固 与成人HSCT中的标准剂量QIV相比，与HD-TIV相关的系统性不良事件 接收者；特定目的3）定义HAI滴度，体内和B细胞表型之间的关系， 以及接受HSCT接受者的体外影响特异性T和B细胞反应接受HD-TIV 或标准剂量QIV。受试者将以1：1的方式随机分配，以接受2017-2018的2剂 HD-TIV（每种影响抗原的60μg）或2剂标准剂量QIV（每种影响15µg抗原）。 HAI和微中性化滴度影响为Za病毒抗原，表型B和T细胞反应，B和T细胞 特定的影响力反应，全血数，定量CD4+/CD8+/CD19+水平和定量 血清IgG和IgM浓度将在第一次和第二次疫苗剂量之前测量28-42天 第二次疫苗剂量和第二次疫苗后约7个月后。征求广告活动将 在疫苗后七天记录该主题，并由学习人员进行电话/电子邮件随访。 这项研究的结果将填补有关HSCT接受者影响力疫苗反应的知识的空白 并将指导该脆弱人群中的疫苗建议。