HLA linked immune response to S and pre‐S2 gene products in hepatitis B vaccination

Abstract

In order to detect a possible HLA linked genetic control of human immune responses to hepatitis B virus, forty healthy adult persons of the same age typed for HLA-A, -B and -DR antigens, were vaccinated against virus hepatitis B and sequentially tested for anti-HBs and anti-pre-S2 antibodies. They received three injections of Hevac-B Pasteur vaccine, the second 1 month and the third 3 months after the first. Following the third immunization, 38 individuals (95%) had a protective level of anti-HBs antibodies and 17 (42.3%) had a positive level of anti-pre-S2 antibodies. HLA-A11 antigen was significantly more frequent (pc = 0.007) among anti-HBs high responders than low responders. In addition, anti-HBs high responders were more frequently HLA-DR1, and less frequently HLA-DR4 and DR7 positive; corrected values, however, were not significant. Anti-pre-S2 high responders showed an apparent increase of HLA-B7, B14 or DR3 antigens, when compared to low responders (pc not significant).

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.…”

Trans-activation of HLA-DR gene by hepatitis B virus X gene product.

“…Expression of both envelope (pre-S1, pre-S2, and S) and nucleocapsid (HBcAg) antigens has been reported on the membrane of HBV-infected hepatocytes in close proximity to infiltrates of mononuclear inflammatory cells containing T lymphocytes (15,16). The immune response to HBV antigens has been shown to be major histocompatibility complex (MHC)-restricted in mice (39), and the human immune response to HBV envelope antigens is also HLA-restricted (40). Both HLA class I and II expression is observed during HBV infection in areas of inflammation and necrosis (24,25).…”

“…Among HBV genes, the X gene product, now acknowledged to be a trans-activator, stimulates expression of the HLA-DR gene by directly interacting with its upstream regulatory element(s). The X protein has been shown to trans-activate promoters/enhancers of several viral and cellular genes (5,6,40). Recent studies have demonstrated that a truncated sequence derived from S ORF displays trans-activation function (41).…”

A prospective study of in vitro anti‐HBs producing B cells (spot‐ELISA) following primary and supplementary vaccination with a recombinant hepatitis B vaccine in insulin dependent diabetic patients and matched controls

“…Eventually 9/10 controls and 5/10 IDDM patients acquired anti-HBs levels above 10 IU/L. Genetic (MHC) factors are possibly involved, but only few investigators have explored the field of nonresponsiveness to hepatitis B vaccine and HLA-type [Hashi-mot0 et al, 1985;Craven et al, 1986;Marescot et al, 1989;Nepom, 1989;Alper et al, 19891. HLA-DR7 and HLA-DR3 have been implicated, but no conclusive data have been produced yet.…”