Abstract

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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI048793-04
Application #
6697431
Study Section
Epidemiology and Disease Control Subcommittee 2 (EDC)
Program Officer
Cassetti, Cristina
Project Start
2001-02-01
Project End
2006-01-31
Budget Start
2004-02-01
Budget End
2005-01-31
Support Year
4
Fiscal Year
2004
Total Cost
$352,750
Indirect Cost

  Institution

Name
Mayo Clinic, Rochester
Department
Type
DUNS #
006471700
City
Rochester
State
MN
Country
United States
Zip Code
55905

  Publications

Voigt, Emily A; Haralambieva, Iana H; Larrabee, Beth L et al. (2018) Polymorphisms in the Wilms Tumor Gene Are Associated With Interindividual Variations in Rubella Virus-Specific Cellular Immunity After Measles-Mumps-Rubella II Vaccination. J Infect Dis 217:560-566
Haralambieva, Iana H; Gibson, Michael J; Kennedy, Richard B et al. (2017) Characterization of rubella-specific humoral immunity following two doses of MMR vaccine using proteome microarray technology. PLoS One 12:e0188149
Haralambieva, Iana H; Ovsyannikova, Inna G; Kennedy, Richard B et al. (2017) Genome-wide associations of CD46 and IFI44L genetic variants with neutralizing antibody response to measles vaccine. Hum Genet 136:421-435
Ovsyannikova, Inna G; Larrabee, Beth R; Schaid, Daniel J et al. (2017) Immunoglobulin GM and KM genes and measles vaccine-induced humoral immunity. Vaccine 35:5444-5447
Ovsyannikova, Inna G; Schaid, Daniel J; Larrabee, Beth R et al. (2017) A large population-based association study between HLA and KIR genotypes and measles vaccine antibody responses. PLoS One 12:e0171261
Schaid, Daniel J; Haralambieva, Iana H; Larrabee, Beth R et al. (2017) Heritability of vaccine-induced measles neutralizing antibody titers. Vaccine 35:1390-1394
Voigt, Emily A; Ovsyannikova, Inna G; Haralambieva, Iana H et al. (2016) Genetically defined race, but not sex, is associated with higher humoral and cellular immune responses to measles vaccination. Vaccine 34:4913-4919
Lambert, Nathaniel D; Haralambieva, Iana H; Kennedy, Richard B et al. (2015) Polymorphisms in HLA-DPB1 are associated with differences in rubella virus-specific humoral immunity after vaccination. J Infect Dis 211:898-905
Lambert, Nathaniel; Strebel, Peter; Orenstein, Walter et al. (2015) Rubella. Lancet 385:2297-307
Haralambieva, Iana H; Kennedy, Richard B; Ovsyannikova, Inna G et al. (2015) Variability in Humoral Immunity to Measles Vaccine: New Developments. Trends Mol Med 21:789-801

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