Abstract
Human antibody response to measles vaccine is highly variable in the population. Host genes contribute to inter-individual antibody response variation. The killer cell immunoglobulin-like receptors (KIR) are recognized to interact with HLA molecules and possibly influence humoral immune response to viral antigens. To expand on and improve our previous work with HLA genes, and to explore the genetic contribution of KIR genes to the inter-individual variability in measles vaccine-induced antibody responses, we performed a large population-based study in 2,506 healthy immunized subjects (ages 11 to 41 years) to identify HLA and KIR associations with measles vaccine-induced neutralizing antibodies. After correcting for the large number of statistical tests of allele effects on measles-specific neutralizing antibody titers, no statistically significant associations were found for either HLA or KIR loci. However, suggestive associations worthy of follow-up in other cohorts include B*57:01, DQB1*06:02, and DRB1*15:05 alleles. Specifically, the B*57:01 allele (1,040 mIU/mL; p = 0.0002) was suggestive of an association with lower measles antibody titer. In contrast, the DQB1*06:02 (1,349 mIU/mL; p = 0.0004) and DRB1*15:05 (2,547 mIU/mL; p = 0.0004) alleles were suggestive of an association with higher measles antibodies. Notably, the associations with KIR genotypes were strongly nonsignificant, suggesting that KIR loci in terms of copy number and haplotypes are not likely to play a major role in antibody response to measles vaccination. These findings refine our knowledge of the role of HLA and KIR alleles in measles vaccine-induced immunity.
Highlights
Host genetic factors are believed to be responsible for up to 90% of measles vaccine-induced inter-individual antibody response variations [1]
Because there is strong linkage disequilibrium among the alleles from the Human Leukocyte Antigen (HLA)-B and HLA-C loci, we evaluated the joint effects of B alleles and C alleles, adjusted for each other
We demonstrated suggestive associations between several allelic variants of the HLA-B, -DQB1, and -DRB1 loci and neutralizing antibody titers
Summary
Host genetic factors are believed to be responsible for up to 90% of measles vaccine-induced inter-individual antibody response variations [1]. Among these genetic factors, the Human Leukocyte Antigen (HLA) genes (on chromosome 6p21) have been a focus of interest since these highly polymorphic HLA genes play an important role in the regulation of immune response, including immunity to measles virus [2]. The main role of HLA class I and class II. HLA and KIR associations with measles vaccine-induced antibodies
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