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Abstract
Grant Number: 5R01AI048793-04 Project Title: IMMUNOGENETIC MECHANISMS OF VACCINE RESPONSE
PI Information: Name Title POLAND, GREGORY A. poland.gregory@mayo.edu DIRECTOR, MAYO VACCINE RESEARCH GROUP Abstract: 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.
Public Health Relevance:
This Public Health Relevance is not available.Thesaurus Terms:
Rubivirus, active immunization, human therapy evaluation, immunogenetics, viral vaccine
antiviral antibody, genetic polymorphism, histocompatibility gene, live vaccine, measles vaccine, measles virus, microorganism immunology, mumps virus
adolescence (12-20), clinical research, human subject, middle childhood (6-11), preschool child (1-5)
Institution: MAYO CLINIC COLL OF MEDICINE, ROCHESTER 200 1ST ST SW ROCHESTER, MN 55905 Fiscal Year: 2004 Department: Project Start: 01-FEB-2001 Project End: 31-JAN-2006 ICD: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES IRG: EDC