Abstract

Measles remains a significant public health concern, and the NIH has committed itself to the development of a better vaccine against measles and the exploration of the immunogenetics of vaccine responsiveness.
The Specific Aims of this research application extend previous data of the investigators by examining the influence of two antigen-processing genes (TAP: Transporter associated with Antigen Processing and HLA-DM) upon variations in antibody levels following measles vaccination.
Specific Aim 1) By drawing upon the original cohort of Rochester school children, this study will provide estimates of the association between antibody level following measles vaccine and specific alleles of TAP and DM alleles in human subjects.
Specific Aim 2) This study will also estimate the association between antibody level following measles vaccine and homozygosity of specific TAP and DM alleles in human subjects.
Specific Aim 3) Using class I and II HLA results from the investigators current study, they will estimate the association between the antibody level following measles vaccination and extended haplotypes of HLA including class I and II as well as TAP and DM. Hypotheses under study examine children with both extremes of measles antibody levels following vaccination: low and high antibody levels.
Specific Aim 4) Studying the parents and siblings of the children with both extremes of antibody levels will permit examination of the genetic linkage between antibody levels following measles vaccination and TAP and DM loci within pedigrees. By focusing upon genes within the Major Histocompatibility Complex (MHC) responsible for antigen transport, processing, and presentation, these four aims will provide data that will help define genetic influences on measles antibody levels following vaccination. The public health relevance of this work may be significant since such information is likely to generalize to other live virus vaccines such as rubella, mumps, and varicella, and be instrumental in developing the next generation of measles vaccines.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI033144-08
Application #
6373293
Study Section
Special Emphasis Panel (ZRG4-EDC-2 (02))
Program Officer
Meegan, James M
Project Start
1993-09-30
Project End
2002-05-31
Budget Start
2001-06-01
Budget End
2002-05-31
Support Year
8
Fiscal Year
2001
Total Cost
$203,481
Indirect Cost

  Institution

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

  Publications

Poland, G A; Ovsyannikova, I G; Kennedy, R B (2018) Personalized vaccinology: A review. Vaccine 36:5350-5357
Haralambieva, Iana H; Kennedy, Richard B; Simon, Whitney L et al. (2018) Differential miRNA expression in B cells is associated with inter-individual differences in humoral immune response to measles vaccination. PLoS One 13:e0191812
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
Schaid, Daniel J; Haralambieva, Iana H; Larrabee, Beth R et al. (2017) Heritability of vaccine-induced measles neutralizing antibody titers. Vaccine 35:1390-1394
Poland, Gregory A; Whitaker, Jennifer A; Poland, Caroline M et al. (2016) Vaccinology in the third millennium: scientific and social challenges. Curr Opin Virol 17:116-125
Haralambieva, Iana H; Zimmermann, Michael T; Ovsyannikova, Inna G et al. (2016) Whole Transcriptome Profiling Identifies CD93 and Other Plasma Cell Survival Factor Genes Associated with Measles-Specific Antibody Response after Vaccination. PLoS One 11:e0160970
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

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