Clear and independent associations of several HLA-DRB1 alleles with differential antibody responses to hepatitis B vaccination in youth

Abstract

To conWrm and reWne associations of human leukocyte antigen (HLA) genotypes with variable antibody (Ab) responses to hepatitis B vaccination, we have analyzed 255 HIV-1 seropositive (HIV + ) youth and 80 HIV-1 seronegatives (HIV ¡ ) enrolled into prospective studies. In univariate analyses that focused on HLA-DRB1, -DQA1, and -DQB1 alleles and haplotypes, the DRB1*03 allele group and DRB1*0701 were negatively associated with the responder phenotype (serum Ab concentration¸10 mIU/mL) (P = 0.026 and 0.043, respectively). Collectively, DRB1*03 and DRB1*0701 were found in 42 (53.8%) out of 78 non-responders (serum Ab <10 mIU/mL), 65 (40.6%) out of 160 medium responders (serum Ab 10-1,000 mIU/ mL), and 27 (27.8%) out of 97 high responders (serum Ab >1,000 mIU/mL) (P < 0.001 for trend). Meanwhile, DRB1*08 was positively associated with the responder phenotype (P = 0.010), mostly due to DRB1*0804 (P = 0.008). These immunogenetic relationships were all independent of nongenetic factors, including HIV-1 infection status and immunodeWciency. Alternative analyses conWned to HIV + youth or Hispanic youth led to similar Wndings. In contrast, analyses of more than 80 non-coding, single nucleotide polymorphisms within and beyond the three HLA class II genes revealed no clear associations. Overall, several HLA-DRB1 alleles were major predictors of diVerential Ab responses to hepatitis B vaccination in youth, suggesting that T-helper cell-dependent pathways mediated through HLA class II antigen presentation are critical to eVective immune response to recombinant vaccines.

HLA alleles associated with the adaptive immune response to smallpox vaccine: a replication study

“…Interestingly, the HLA-DRB1*08 allele has been associated with differential antibody responses to other vaccines, including measles vaccine (Ovsyannikova et al 2004). Consistent with the above finding, the HLA-DRB1*08 (DRB1*08:04) allele was reported to be associated with hepatitis B vaccine responder phenotype in young Hispanics (Li et al 2009). The difference in effect of these DRB1*04:03 and DRB1*08:01 alleles on vaccine immune response outcome may be due to differences in vaccine antigens (such as vaccinia, measles, hepatitis B) and, hence, viral-specific antigen processing and presentation.…”

Duration of Protection After Infant Hepatitis B Vaccination Series

“…Recent advances in examining the association of immune response between "high" and "low" responders to vaccines with genotype differences have emphasized the role of genetic make-up in vaccine response. [22][23][24][25] Race may serve as a proxy for these genetic differences. The clinical significance of this finding is unclear, however, because race was not significantly associated with the more clinically relevant outcome of seroprotection.…”

Humoral responses to independent vaccinations are correlated in healthy boosted adults

“…Second, vaccination responses may be influenced by genetic variations that influence overall immunity. As opposed to HLA alleles, which have been associated with skewed presentation of antigens and therefore responsiveness to individual vaccinations [17, 18, 43–45], genes that are virus- or inflammation-specific could theoretically affect more than one vaccine response. Associations between non-HLA genes and vaccine responses have only just begun to be explored [19, 46], but confirmation of non-HLA genetic associations may allow for improved individualization of vaccinations.…”