Measles kills one million persons each year and is slated for worldwide eradication. Our broad objective is to determine the genetic mechanisms that influence the immune response (humoral and cell-mediated) to viral vaccines. In this continuation, we focus on the influence of class I and II HLA genes on measures of the cellular immune response to established live viral vaccine measles as a model with which to explore the influence of immunogenetics on the variability of vaccine response. Our central hypothesis is that polymorphisms of the HLA genes influence the cellular immune responses to live viral vaccines. To test this hypothesis, we propose studies with the following Specific Aims: (1) to estimate associations between specific HLA class I alleles (A, B, and C) and cellular immune responses following measles vaccine; (2) to estimate associations between specific HLA class II alleles (DRB, DQA, DQB, DPA, and DPB) and cellular immune responses following measles vaccine; (3) to estimate the effects of genetic variation (homozygosity and multigenic effects) across the class I and II HLA alleles and cellular immune responses following vaccine; and (4) to estimate associations between cellular and humoral immune responses to measles vaccine within individuals, and to explore the effect of genetic factors on these associations.
The aims of this research application extend our data on measles vaccine immuno-genetics and humoral immunity by examining the influence of class I and II HLA genes upon variations in cellular immune responses following measles immunization. The application is innovative conceptually as it examines the effect of immunogenetics on variability of vaccine response. The significance of this information is that it will provide a framework for estimating the contribution of HLA variability on variability in cellular immune responses as well as provide knowledge important to the development of new viral vaccines (HIV, HPV, Hepatitis C, and others) in a genetically heterogeneous population.
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