Humoral and cellular immune responses to hepatitis B vaccination in hepatitis B surface antigen-carrier children who cleared serum- hepatitis B surface antigen

Abstract

Chronic hepatitis B surface antigen (HBsAg) / cells enhanced the whereas it persisted in others, is unclear. In addition, HBsAg blastogenic response in group 3 but did not rewhether the carrier children who cleared the HBsAg without verse the unresponsiveness in group 1 and group 2 subdetectable anti-HBs may benefit from hepatitis B immunizajects. The addition of interleukin (IL)-2 in culture retion is also unknown. versed unresponsiveness in all cases except one case inTo study the immune unresponsiveness to HBsAg at the group 1. Compared with before vaccination, PBMC from genetic and cellular levels in carrier children who cleared group 2 subjects produced significantly less interferon serum HBsAg but failed to develop anti-HBs, we vaccinated gamma (IFN-g) and more IL-4 in response to HBsAg after those subjects with recombinant hepatitis B vaccine and vaccination, a cytokine response not observed in group aimed to determine (1) whether anti-HBs production could 1 subjects. HLA typing indicated that 3 of 10 patients in be elicited or enhanced, (2) whether HBsAg-specific T cells group 1 (30%) and 1 of 5 patients in group 2 (20%) had could be activated in vivo, and (3) whether suppression or HLA-DRw14-DRw52, a marker previously linked to low defect of antigen presentation is involved in the unresponanti-HBs response to hepatitis B vaccine in Taiwan. We siveness. Because analysis of cytokine produced by peripheral conclude that the underlying causes of poor anti-HBs blood mononuclear cells (PBMC) in response to HBsAg may response in group 1 subjects are multifactorial, includaid in the understanding of the mechanisms underlying the ing specific failure of antigen presentation or T-cell actiimmune response to HBsAg, we examined the cytokine provation, or the lack of T helper (Th)2 cell-like response duction of the immune response to HBsAg in our subjects to HBsAg. HLA-DRw14-DRw52 does not confer absolute to determine whether the cytokine pattern is related to the nonresponsiveness to HBsAg. These patients are not unresponsiveness. By HLA typing, we attempted to show benefited by hepatitis B immunization. (HEPATOLOGY whether HLA phenotype can predict a poor anti-HBs re-1996;24:1355-1360.) sponse in carriers who cleared serum HBsAg. PATIENTS AND METHODS Patients.A total of 415 HBV carrier children from the Department of Pediatrics, National Taiwan University Hospital, were checked for serum HBV markers and had conventional liver profiles every 6 we studied their immune response to HBsAg. There were 10 boys feron gamma; S/N, sample cpm per negative control mean cpm; Th, T helper cell. From the

Hepatitis B Surface Antigen Could Contribute to the Immunopathogenesis of Hepatitis B Virus Infection

“…In the resolution of HBV infection, efficient recognition of the intracellular HBV antigens by the host immune cells is essential [32, 33, 44, 45]. It has been shown that the cellular immune system, including CTL, Th1, and Tregs, plays a central role in the control of virus infection.…”

Immunogenic Effects of Woodchuck Hepatitis Virus Surface Antigen Vaccine in Combination with Antiviral Therapy: Breaking of Humoral and Cellular Immune Tolerance in Chronic Woodchuck Hepatitis Virus Infection

“…About 90% of HBV-naïve vaccine recipients develop strong anti-HBs antibody and T cell responses to HBsAg [20][21][22][23][24]. Vaccination of chronic HBV carriers with HBsAg vaccines, however, elicits only weak and transient anti-HBs antibodies and HBsAg-specific T cell responses in a low proportion of such patients [21,25,26]. Sustained reductions in viremia in chronic HBV carriers receiving HBsAg vaccine have been observed in some cases as well [26,27].…”

Comparative analysis of HLA restriction and cytokine production in hepatitis B surface antigen-specific T cells from low- and high-antibody responders in vaccinated humans

“…The mechanisms of low responsiveness remain unclear, although several studies have revealed evidence relevant to the mechanisms. The absence of dominant immune response genes (Alper et al 1989) or the presence of dominant immune suppression genes located in the MHC region (Watanabe et al 1988;Hatae et al 1992); defect of T-cell-APC interaction (Milich et al 1984); selective killing of HBsAg-specific B cells by MHC-restricted cytotoxic T-lymphocytes (CTL) (Barnaba et al 1990); imbalanced Th1/Th2 response to HBsAg (Vingerhoests et al 1994;Hsu et al 1996;Honorati et al 1997;Bocher et al 1999); and the elimination of HBsAgspecific T cells during thymic or postthymic repertoire maturation (Wismans et al 1988) are mechanisms that have been proposed. Because the human population is largely outbred and carries varied HLA antigens, reflecting the marked polymorphism of the immune system, and because the population is exposed to diverse antigens, it is not easy to simply uncover the mechanisms of non/low responsiveness.…”