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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要流感病毒是免疫功能低下者的严重病原体，尤其是造血干细胞然而，这些人对三价灭活流感反应不佳。疫苗 (TIV)。高剂量 (HD)-TIV 对 65 岁以上的成年人具有增强的免疫原性和功效。目前尚不清楚 HD-TIV 对于严重免疫功能低下的人是否安全且具有免疫原性。 TIV 免疫原性的标准衡量标准是血凝抑制 (HAI) 滴度。我们的建议是，与标准剂量的四价灭活疫苗相比，HD-TIV 更具免疫原性成人 HSCT 接受者接种流感疫苗 (QIV)，HAI 抗体对甲型流感的反应较高即可证明这一点拟议的研究是一项多中心、II 期免疫原性和安全性试验，比较两种剂量。成人 HSCT 接受者中 HD-TIV 与标准剂量 QIV 的比较共有 138 名患者（≥18 岁）。接受同种异体 HSCT 且移植后 3-23 个月的患者将在以下临床中心入组：范德比尔特大学医学中心（主导站点）；西北大学范伯格医学院，弗雷德哈钦森癌症研究中心；阿拉巴马大学伯明翰医学院。目标如下：具体目标 1) 确定-TIV 与标准剂量 QIV 相比是否会增加 HAI 滴度提高 ≥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) 特定目标 2) 确定引起的局部注射部位不良事件的频率和严重程度并引起与成人 HSCT 中标准剂量全身 QIV 相比，HD-TIV 相关的不良事件受者；具体目标 3) 定义 HAI 滴度、体内 T 和 B 细胞表型之间的关系，以及接受 HD-TIV 的成人 HSCT 受者的体外流感特异性 T 和 B 细胞反应受试者将以 1:1 的方式随机接受 2017-2018 年的 2 剂疫苗。 HD-TIV（每种流感抗原 60 µg）或 2 剂标准剂量 QIV（每种流感抗原 15 µg）。 HAI 和流感病毒抗原的微中和滴度、表型 B 和 T 细胞反应、B 和 T 细胞特定流感反应、全血细胞计数、CD4+/CD8+/CD19+ 水平和定量将在第一剂和第二剂疫苗接种前 28-42 天测量血清 IgG 和 IgM 浓度在第二次疫苗接种后，以及在第二次疫苗接种后大约 7 个月，将出现不良事件。由受试者在接种疫苗后 7 天进行记录，并由研究人员通过电话/电子邮件进行跟进。这项研究的结果将填补 HSCT 受者流感疫苗反应的知识空白并将指导针对这一弱势群体的疫苗建议。