Genetic Prediction of Nonresponse to Hepatitis B Vaccine

Abstract

In previous studies of the antibody response to hepatitis B vaccine in 598 subjects who received a full course of vaccination, we observed a bimodal response, with about 14 percent producing less than approximately 1000 radioimmunoassay (RIA) units. An analysis of the major histocompatibility complex (MHC) HLA and complement types of 20 of the subjects with the lowest responses indicated a greater-than-expected number of homozygotes for the extended or fixed MHC haplotype [HLA-B8, SC01, DR3]. This finding suggested that the lack of a normal response was a recessive MHC-linked trait. In this study, we prospectively vaccinated five homozygotes and nine heterozygotes for this haplotype in the expectation that the homozygotes would produce much lower levels of antibody than the heterozygotes. When the antibody response was assessed two months after the third injection, four of the five homozygotes had produced very low levels (approximately 1000 units or less) of antibody (mean, 467 RIA units; range, less than 8 to 1266), whereas all nine heterozygotes produced more than 2500 RIA units (mean, 15,608; range, 2655 to 28,900) (P less than 0.01). We conclude that the usual response to hepatitis B surface antigen is due to the presence of a dominant immune-response gene in the MHC and that a low response is due to the absence of such a gene and the presence on both chromosomes of MHC haplotypes (such as [HLA-B8, SC01, DR3]) that indicate such a response.

T cell responses to hepatitis B surface antigen are detectable in non-vaccinated individuals

“…Individuals responding to vaccination with the induction of a high anti-HBsAg titer showed a strong T cell response non-responsiveness (HBsAg titer < 10 kU/L) to vaccination are associated with certain human leukocyte antigen (HLA)-class Ⅱ alleles. DRB1*0301, DRB1*0701, and DQB1*0201 [5,8,9] were shown to have a higher prevalence in non-responders, whereas other antigens (DRB1*0101, *1301, *1501, and DPB1*0401) seem to mediate strong immune responses [9][10][11][12] . Higher age, obesity, male gender, smoking, and chronic dialysis are risk factors for a non-/ low-responsiveness [8,9,[13][14][15] .…”

Association between hepatitis B virus infection and HLA-DR type in Korea

“…There have been other reports of decreased immune response to HBsAg in persons with HLA-DR3. [12][13][14] Although the mechanism of susceptibility to chronic persistent HBV infection is not well clarified, it is known to be influenced by host immunogenetic factors. 8,15 A strong virusspecific CD4 ϩ and CD8 ϩ T-lymphocyte response to HBV has been associated with viral clearance, but comparatively little is known about the factors, which determine the individual' s ability to mount such a T-cell response.…”

New genetic associations detected in a host response study to hepatitis B vaccine

“…3 The reasons for these individual failures are multiple, including physical factors such as age, gender, obesity, immunosuppression and smoking 4,5 as well as variation in genes of the immune system. [6][7][8][9] Several polymorphisms of the human leukocyte antigen (HLA) loci have been linked to variations in the immune response both to vaccination as well as natural hepatitis B infections. In particular, HLA-DR3 and DR7, which are in linkage disequilibrium with HLA-DQ2, have been shown to be associated with nonresponsiveness, 10,11 whereas DRB1* alleles 1, 11 and 15 have been shown to be associated with a good response to HBV vaccination.…”