IMMUNOGENETIC MECHANISMS OF VACCINE RESPONSE

疫苗反应的免疫遗传学机制

• 批准号: 6497390
• 负责人: Gregory A. Poland
• 金额: $ 35.28万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-02-01 至 2006-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6497390
• 关键词: Rubivirus; active immunization; adolescence (12-20); antiviral antibody; clinical research; genetic polymorphism; histocompatibility gene; human subject; human therapy evaluation; immunogenetics; live vaccine; measles vaccine; measles virus; microorganism immunology; middle childhood (6-11); mumps virus; preschool child (1-5); viral vaccines

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.

描述：我们广泛的，长期的目标是确定遗传