Host SNPs and Altered Responses to Influenza Vaccine

宿主 SNP 和流感疫苗反应的改变

• 批准号: 6741842
• 负责人: YI-WEI TANG
• 金额: $ 7.55万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-05-01 至 2006-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6741842
• 关键词: clinical research; drug adverse effect; gene dosage; genes; genetic promoter element; human tissue; immunogenetics; influenza vaccines; influenzavirus A; interleukin 10; lectin; patient oriented research; polymerase chain reaction; single nucleotide polymorphism; tumor necrosis factor alpha

DESCRIPTION (provided by applicant): Inactivated influenza virus vaccines have been progressively improved over the past several decades to decrease reactogenicity and standardize antigenic content. Despite such progress, some otherwise healthy individuals either develop poor immune responses or experience adverse reactions to vaccination, strongly suggesting that host factors may play a role in determining responses to influenza vaccine. Various host immunogenetic polymorphisms are associated with host susceptibility and clinical manifestations of some infectious diseases, either by encoding altered gene products or by affecting transcriptional regulation. The present study will correlate polymorphisms of three host immunogenetic factors: the mannose binding lectin (MBL) gene, the tumor necrosis factor (TNF)-alpha and interleukin10 (IL-10) promoters, with host immune responses to inactivated influenza vaccines. Volunteers participating in previously conducted inactivated influenza vaccine trials who developed either decreased immune responses or increased adverse events to vaccination will be compared with those who developed brisk immune response and suffered no adverse events associated with vaccination. Subjects will be matched for age, gender and race. Genomic DNA will be extracted from frozen archived serum specimens obtained in a large previously conducted NIH-funded influenza vaccine field trial. The host polymorphisms in the MBL exon 1 genome and in the TNF-alpha and IL-10 promoter regions will be determined by PCR-based techniques. Defining host molecular determinants of influenza vaccine immunogenecity and adverse events may foster strategies to enhance vaccine effectiveness and safety in large patient populations. It is fully realized that the analysis of these three host polymorphisms may be too limited to pinpoint the genetic basis of variability in vaccine-induced responses, but the archived genomic DNA generated from the proposed studies will be used to examine additional, yet to be identified, host polymorphisms in the future.

描述(由申请人提供)：灭活流感病毒疫苗在过去几十年中已逐步改进，以降低反应性和标准化抗原含量。尽管取得了这些进展，但一些本来健康的人要么免疫反应差，要么对接种疫苗产生不良反应，强烈表明宿主因素可能在决定对流感疫苗的反应中发挥作用。宿主免疫遗传多态与宿主易感性和某些感染性疾病的临床表现有关，可通过编码改变的基因产物或通过影响转录调控来实现。本研究将探讨三种宿主免疫遗传因子甘露糖结合凝集素(MBL)基因、肿瘤坏死因子(TNF)-α和白介素10(IL-10)启动子的多态性与流感灭活疫苗免疫应答的关系。参与以前进行的灭活流感疫苗试验的志愿者对疫苗的免疫反应减弱或不良事件增加，将与那些免疫反应强烈且未遭受与疫苗接种相关的不良事件的志愿者进行比较。受试者将在年龄、性别和种族方面进行匹配。基因组DNA将从NIH资助的大规模流感疫苗现场试验中获得的冷冻存档血清样本中提取。MBL外显子1基因组以及肿瘤坏死因子-α和白介素10启动子区域的宿主多态将通过基于PCR的技术来确定。确定流感疫苗免疫原性和不良事件的宿主分子决定因素可能会促进在大量患者群体中提高疫苗有效性和安全性的策略。人们充分认识到，对这三种宿主多态的分析可能过于有限，无法准确定位疫苗诱导反应中可变性的遗传基础，但拟议研究产生的存档基因组DNA将在未来用于检查其他尚未鉴定的宿主多态。