Human Leukocyte Antigen Haplotypes in the Genetic Control of Immune Response to Measles‐Mumps‐Rubella Vaccine

Abstract

To elucidate the contribution of human leukocyte antigen (HLA) haplotypes and their genotypic combinations to immune status after measles-mumps-rubella (MMR) vaccination) and higher rubella virus-specific lymphoproliferation ( ). Better char-P p .02 P p .002 acterization of such HLA profiles could inform and improve the design of novel epitope-rich vaccines and help to predict protective immune responses at the individual and population level.Variation in immune responses to live measles-mumpsrubella (MMR) vaccine has been associated with polymorphisms in class I and class II genes within the HLA complex [1][2][3]. Associations between individual class I and class II alleles and measures of humoral (serum antibody) and cell-mediated (lymphocyte proliferation) immune responses to MMR vaccine have confirmed the importance of genetic polymorphisms in the HLA

Human leukocyte antigen and interleukin 2, 10 and 12p40 cytokine responses to measles: Is there evidence of the HLA effect?

“…Our previous work has suggested that humoral and cellular immune responses to measles vaccine are genetically restricted by HLA genes [22][23][24]. Further, we demonstrated that the HLA genes may also play a role in measles-specific cytokine responses and demonstrated significant associations with measles-induced IFN-γ and IL-4 secretion and HLA alleles [25,26].…”

“…A study of twins demonstrated that variations in antibody levels to measles vaccine showed a high degree of heritability (88.5%) [30]. Prior population-based studies found associations with both class I and class II alleles and measles vaccine immune response [22][23][24]. Subsequent studies suggest the significance of HLA genes in measles virus-specific IFN-γ and IL-4 cytokine immune responses [25,26].…”

Vaccinomics: Current Findings, Challenges and Novel Approaches for Vaccine Development

“…For example, HLA class I, in particular the B*8 (p=0.001), B*13 (p=0.004), and B*44 (p=0.03) alleles are associated with IgG seronegativity after a single dose of measles vaccine (14). We demonstrated that the A*29-C*16-B*44 haplotype is associated with low levels of IgG antibody to measles virus (p=0.08) after two doses of measles vaccine ( Table I) (15). Furthermore, the A*26-C*12-B*38 haplotype is associated with high lymphoproliferative responses to measles vaccine (p=0.02).…”

“…In a cohort of 346 healthy children, DQB1*0201 (p=0.04), DQB1*0402 (p=0.02), DQA1*0401 (p=0.003), DRB1*0301 (p=0.02), DRB1*0801 (p=0.02), DRB1*1201 (p=0.04), and DRB1*1302 (p=0.01) alleles were significantly associated with low lymphoproliferative responses to mumps vaccine (18). Interestingly, subjects who carried the DRB1*03-DQB1*02-DPB1*04 haplotype had high lymphoproliferative responses to both measles (p=0.01) and mumps viruses (p=0.006) (15). A strong association was found between many alleles of the HLA-DQA1 (*0103, *0301, *0303) (global p value=0.02) and HLA-DQB1 (*0202, *0302, *0603) (global p value= 0.007) loci and inter-individual variations in rubella virus-induced IL-2 secretion (19).…”

“…SNPs (rs3740996 and rs10838525) in the innate TRIM5 gene coding regions were associated with rubella-specific TNF-α and IL-2/GM-CSF, respectively. These two SNPs have been previously demonstrated to have func- (15) tional roles in regard to antiviral activity (30,31,34,35). Furthermore, we found 23 associations (p<0.05) between genetic variants within the 2′-5′-oligoadenylate synthetase (OAS) gene, and rubella-induced IL-2, IL-10, IL-6 secretion and antibody levels (36).…”