IMMUNOGENETIC MECHANISMS OF VACCINE RESPONSE

描述：我们广泛的、长期的目标是确定 影响免疫反应的机制(抗体水平和 对病毒疫苗的淋巴增殖反应)。我们建议研究 人类白细胞抗原I、II类基因对慢性非典型肺炎免疫应答的影响 活病毒疫苗-风疹-作为模型。我们还将确定这些 这些发现是风疹所特有的，或者可以推广到同时使用。 活病毒(麻疹和腮腺炎)疫苗。我们的中心假设是基因 人类白细胞抗原系统的多态显著影响人类免疫应答 活病毒疫苗。为了测试我们的特定假设，我们提出了以下研究 具体目标如下：1)评估特定目标之间的关联 人类白细胞抗原I类基因(A、B和C)的等位基因与随后的免疫反应 风疹疫苗在人体内的免疫，2)评估风疹疫苗与风疹疫苗之间的关系 人类白细胞抗原II类基因的特定等位基因(DRB、DQA、DQB、DPA和DPB)，以及 风疹疫苗免疫后的免疫反应，3)评估风疹疫苗的效果 I类人群的遗传变异(纯合性和多基因交互作用) 风疹后的和/或人类白细胞抗原II类基因与免疫应答 免疫，以及4)确定疫苗诱导免疫的特异性 反应关联(抗体和淋巴增殖反应)如下 风疹疫苗免疫与其他活病毒模型的比较 疫苗(麻疹和腮腺炎)。本研究方案的研究目的是扩展 我们关于麻疹疫苗免疫遗传学的NO1和RU 1数据通过检查 I类(A、B、C)和II类(DRB、DQA、DQB、DPA、DPB)人类白细胞抗原基因的影响 根据免疫反应的变化(定义为抗体水平和 风疹疫苗接种后的淋巴增殖反应)。我们的发现可能 允许关于免疫应答的一般性免疫遗传学结论 病毒疫苗。我们的研究还可能指导新疫苗的开发(艾滋病毒， HPV、丙型肝炎和其他)，并将有助于识别实际 与遗传异种的免疫反应变异有关的表位 异质种群。

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.