IMMUNOGENETIC MECHANISMS OF VACCINE RESPONSE

描述：我们广泛的，长期的目标是确定遗传 影响免疫反应的机制（抗体水平和 淋巴组织增生反应）。我们建议研究 HLA I类和II类基因对免疫应答的影响 活病毒疫苗-风疹-作为模型。我们还将确定这些 结果是风疹特有的或可推广到伴随给药 活病毒（麻疹和腮腺炎）疫苗。我们的核心假设是， HLA系统的多态性显著地影响免疫应答， 活病毒疫苗为了验证我们的具体假设，我们提出了以下研究： 以下具体目的：1）估计特定 HLA I类等位基因（A、B和C）的等位基因，以及 风疹疫苗接种在人类受试者，2）估计之间的关联 HLA II类等位基因的特异性等位基因（DRB、DQA、DQB、DPA和DPB），和 风疹免疫后的免疫应答，3）评估 I类中的遗传变异（纯合性和多基因相互作用） 和/或II类HLA等位基因与风疹后的免疫应答 4）确定疫苗诱导免疫的特异性 反应相关性（抗体和淋巴增生反应） 风疹疫苗免疫与其他活病毒模型比较 麻疹和腮腺炎疫苗。本研究建议的研究目的， 我们的NO 1和RU 1麻疹疫苗免疫遗传学数据，通过检查 I类（A、B、C）和II类（DR B、DQA、DQ B、DPA、DPB）HLA基因的影响 在免疫应答（定义为抗体水平和 淋巴组织增生反应）。我们的研究结果可能 允许关于免疫应答的可推广的免疫遗传学结论， 病毒疫苗我们的研究也可能指导新疫苗的开发（艾滋病毒， HPV，丙型肝炎和其他），并将有助于确定实际的 表位参与免疫反应变异在遗传远交 异质群体

DESCRIPTION: Our broad, long term objective is to determine the genetic mechanisms that influence the immune response (antibody level and lymphoproliferative responses) to viral vaccines. We propose to study the influence of HLA class I and II genes on the immune response to an established live viral vaccine - rubella - as a model. We will also determine whether these findings are specific to rubella or generalizable to concomitantly administered live viral (measles and mumps) vaccines. Our central hypothesis is that genetic polymorphisms of the HLA system significantly influence the immune responses to live viral vaccines. To test our specific hypotheses, we propose studies with the following Specific Aims: 1) To estimate the association between specific alleles of HLA class I alleles (A, B, and C), and immune responses following rubella immunization in human subjects, 2) To estimate the association between specific alleles of HLA class II alleles (DRB, DQA, DQB, DPA, and DPB), and immune responses following rubella immunization, 3) To estimate the effects of genetic variation (homozygosity and multigenic interactions) across the class I and/or class II HLA alleles and immune responses following rubella immunization, and 4) To determine the specificity of vaccine-induced immune response associations (antibody and lymphoproliferative responses) following immunization with rubella vaccine compared to models of other live viral vaccines (measles and mumps). The study aims of this research proposal extend our NO 1 and RU 1 data on measles vaccine immunogenetics by examining the influence of the class I (A, B, C) and II (DRB, DQA, DQB, DPA, DPB) HLA genes upon variations in immune response (defined as antibody levels and lymphoproliferative responses) following rubella immunization. Our findings may allow generalizable immunogenetic conclusions regarding the immune response to viral vaccines. Our study may also guide the development of new vaccines (HIV, HPV, Hepatitis C, and others) and would facilitate identification of the actual epitopes involved in immune response variation in a genetically outbred heterogeneous population.