Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019163 (hepatitis B)
 38,309 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The widely used hepatitis B virus (HBV) vaccines consist of the small hepatitis B surface (SHBs) protein produced in transfected yeast cells. The frequency of non-responders, especially among immunocompromised patients, has increased the demand for a more immunogenic vaccine. We evaluated the immunogenicity of recombinant HBs 20 nm particles secreted by transfected Chinese hamster ovary (CHO) cells, Bio-Hep-B (BioTechnology General Ltd, Israel), and compared it with yeast-derived vaccines. The CHO-derived vaccine contains the small hepatitis B surface antigen (SHBs protein) as the major component, as well as the middle HBs (MHBs, pre-S2) and the large HBs (LHBs, pre-S1) antigens. Nine groups of ten female Balb/c mice, 4-6 weeks old, were injected once intraperitoneally (i.p.) with 0.09, 0.27 or 0.81 micrograms of each of three vaccines: Bio-Hep-B or two conventional yeast-derived recombinant vaccines, Engerix-B (SmithKline Beecham, Belgium) and H-B-Vax II (Merck, Sharp & Dohme, USA) containing only non-glycosylated SHBs antigen. After 30 days, 40% of the mice injected with 0.09 microgram Bio-Hep-B had seroconverted, but none of the mice receiving the same dose of the other vaccines. The immunogenic dose in 50% of the mice at day 14 after injection was 0.13 microgram for Bio-Hep-B, but over 0.81 microgram for the other two vaccines. Mice of the strain B10/M (which are unresponsive to SHBs and MHBs antigens at the T-cell level) developed 100-fold higher anti-HBs titres after immunization with 1 microgram of Bio-Hep-B i.p., as compared with mice receiving the same amount of yeast-derived HBsAg vaccines.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Improved immunogenicity in mice of a mammalian cell-derived recombinant hepatitis B vaccine containing pre-S1 and pre-S2 antigens as compared with conventional yeast-derived vaccines. 753 67

Regulatory T-helper (Th) cells have been categorized into two functional subsets, Th1 and Th2 cells, which produce distinct lymphokines. In general, Th1 cells mediate cellular immune responses and Th2 cells mediate humoral immunity. Recent serological studies suggest that the Th1-Th2 balance may be relevant in acute and chronic hepatitis B virus (HBV) infections. The purpose of this study was to determine the potential of the nucleocapsid antigens (Ags) (hepatitis B core and e Ags [HBc/eAg]) of HBV to preferentially elicit either a Th1 or a Th2 dominant response. For this purpose, H-2 congenic B10.S and B10 mice were immunized with HBc/eAg, and Ag-specific T-cell proliferative responses, T-cell helper function, and T-cell cytokine production were analyzed. The results indicated that B10.S mice preferentially develop a Th1-like response whereas B10 mice preferentially develop a Th2-like response after immunization with HBc/eAg. Furthermore, the preferential Th1 and Th2 response patterns were reproduced when 12-residue peptides representing the dominant HBc/eAg-specific T-cell sites for B10.S (peptide 120-131) and B10 (peptide 129-140) mice were used as immunogens. Therefore, the combination of the T-cell site recognized and the major histocompatibility complex restricting element can in large part determine the Th phenotype of the HBc/eAg-specific T-cell response. Other factors that influenced Th phenotype were the presence of exogenous cytokines, Ag structure, and tissue distribution.
 ...
PMID:Preferential recognition of hepatitis B nucleocapsid antigens by Th1 or Th2 cells is epitope and major histocompatibility complex dependent. 753 65

Previous studies of hepatitis B e antigen (HBeAg)-expressing transgenic (Tg31e) mice have indicated that the degree of T cell tolerance was epitope specific. For example, T cells specific for residues 120-131 of HBeAg are profoundly tolerant, whereas a proportion of T cells specific for residues 129-140 escape tolerance induction in B10. S x B10-Tg31e mice. To understand the basis for differential tolerance towards two T cell sites on the same self antigen, we characterized T cell recognition of HBeAg by primary T cells and T cell hybridomas derived from HBeAg-Tg and non-Tg mice. The self-reactive T cells surviving in B10-Tg31e mice exhibited a unique fine specificity, albeit still focussed on HBeAg residues 129-140, which could be distinguished from the HBeAg-specific T cell repertoire in non-Tg B10 mice. Further, self-reactive T cells were comprised predominantly of Th2-type cells that preferentially evaded tolerance induction as compared to their Th1 counterparts. Because HBeAg may act as a tolerogen during the vertical transmission of chronic hepatitis B virus (HBV) infection, these results suggest that a predominance of HBeAg-specific Th2 cells expressing a limited repertoire may influence the initiation or the maintenance of the HBV chronic carrier state.
 ...
PMID:Characterization of self-reactive T cells that evade tolerance in hepatitis B e antigen transgenic mice. 754 99

We previously developed a transgenic (Tg) murine lineage (B10.S-Tg31e), which secretes the hepatitis B e Ag (HBeAg) into the serum at a concentration of 10 ng/ml. This serum concentration was sufficient to render B10.S-Tg31e mice functionally tolerant at the T cell but not B cell level. To determine the tolerogenic potential of an intracellular form of this Ag, namely the hepatitis B core Ag (HBcAg), expressed outside the thymus, the B10.S-Tg10c lineage was developed. In B10.S-Tg10c mice the HBcAg is expressed as an intracellular "self"-Ag predominantly in the liver, and cannot be detected in the serum, the thymus or in nonthymic lymphoid tissue. Despite the liver-specific and intracellular location of this transgenic self-protein, B10-STg10c mice demonstrate a significant degree of HBcAg-specific T cell tolerance at the level of T cell proliferation. Similarly, in vivo anti-HBc antibody production after HBcAg immunization is significantly reduced as compared with non-Tg littermate controls. No spontaneous anti-HBc antibody is produced in B10.S-Tg10c mice, however, adoptive transfer of HBcAg-specific T cells from non-Tg B10.S mice elicits anti-HBc specific "autoantibody" production. Interestingly, antibodies with specificity for the HBeAg as well as the HBcAg are produced. Antibody production in B10.S-Tg10c mice adoptively transferred with T cells indicates that sufficient native HBcAg can gain access to the extracellular compartment to engage HBcAg-specific B cells that are clearly not tolerant in this model. No liver injury was observed as a consequence of HBcAg expression, even in B10.S-Tg10c mice adoptively transferred with HBcAg-specific T cells. Unless HBcAg is unique in this regard, these results suggest that organ-specific, intracellular self-Ag may be released during normal cell turnover in sufficient concentrations to elicit systemic T cell tolerance. B10.S-Tg10c mice also serve as an immunologic model system for chronic infection with the HBeAg-negative mutant of the hepatitis B virus.
 ...
PMID:Extrathymic expression of the intracellular hepatitis B core antigen results in T cell tolerance in transgenic mice. 828 30

Infants born to hepatitis B e antigen (HBeAg)-positive hepatitis B virus (HBV) carrier mothers invariably become persistently infected. To investigate the role of immunologic tolerance mechanisms in chronic infection of the newborn, we have generated HBeAg-expressing transgenic mice (B10.S-Tg31e). These mice were tolerant to both HBeAg and the nonsecreted HBcAg at the T-cell level. Furthermore, nontransgenic littermates born to HBeAg-expressing mothers showed lowered T-cell responses to HBc/HBe antigens, suggesting that tolerogenic HBeAg may cross the placenta. Tg mice did not produce antibody to HBeAg but did produce immunoglobulin M (IgM) antibodies to HBcAg via a T cell-independent pathway. The coexistence of tolerance to HBc/HBe T-cell determinants and production of antibody to HBcAg in vivo parallels the immunologic status of neonates born to carrier mothers. These observations suggest that expression of HBeAg may represent a viral strategy to guarantee persistence after perinatal infection. Further studies in F1 hybrid Tg mice (B10 x B10.S-Tg31e) illustrated that "self" tolerance to HBeAg is variable, depending on the major histocompatibility complex (MHC) genotype. A proportion of T cells recognizing e129-140 in the context of I-Ab evade induction of tolerance, persist in the periphery, and can be activated in vivo by a single injection of the 12 residue T-cell self-peptide. Furthermore, the self-reactive T cells can cooperate with self-reactive, HBeAg-specific B cells to mediate in vivo production of autoantibody sufficient to neutralize detection of the autoantigen in serum.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Role of T-cell tolerance in the persistence of hepatitis B virus infection. 829 4

Live vaccines based on BRD509, an attenuated S. typhimurium (aroA, aroD) strain, were constructed that directed the expression of hepatitis B core antigen particles (HBcAg) (BRD969) or HBcAg harbouring human papillomavirus type 16 E7 protein sequences (BRD974), under the control of the in vivo inducible nirB promoter. These strains were used to orally or intravenously immunise different inbred mouse strains and humoral, secretory and cellular anti-E7 and anti-HBcAg responses were monitored. Both BRD969 and BRD974 induced anti-HBcAg humoral IgG responses following oral or intravenous immunisation of B10 mice, although responses were higher in BRD969 immunised animals. IgG subclass analysis revealed a predominantly IgG2a response in these animals. BRD974, but not BRD969, induced anti-E7 humoral IgG responses. Anti-HBcAg (BRD969 and BRD974) and anti-E7 (BRD974) IgA responses were detected in the intestines of orally immunised mice. Anti-Salmonella but not anti-HBcAg or anti-E7 T helper cell responses were detected in mice immunised with BRD509, BRD969 and BRD974. Thus Salmonella vaccine strains can be used to efficiently deliver HBcAg and E7 epitopes to the mucosal and systemic immune systems.
 ...
PMID:Immunisation of mice using Salmonella typhimurium expressing human papillomavirus type 16 E7 epitopes inserted into hepatitis B virus core antigen. 878 54

Th1 and Th2 immune responses against antigens can be modulated by the use of adjuvants. Since antibody isotypes (IgG1 and IgG2a) and cytokines induced may reflect the Th differentiation taking place during the immune response, the humoral and cellular immune responses induced in mice against hepatitis B virus surface antigen (HBsAg) were examined when the antigen was either adsorbed to aluminum hydroxyde or administered with a new adjuvant the cationic lipid 3beta-[N-(N',N'-dimethylaminoethane)carbamoyl]cholesterol (DC-Chol). The use of DC-Chol increased antibody responses in responding BALB/c mice, induced more consistent IgG1 and IgG2a antibody responses in OF1 mice and overcame the nonresponse to HBsAg in B10.M mice. Furthermore, DC-Chol was able to induce cellular immune responses to HBsAg. The DC-Chol induced a balanced Th1/Th2 response, which enabled mice to overcome the inherited unresponsiveness to HBsAg encountered with aluminum-adjuvanted vaccine. Thus, the DC-Chol provides a signal to switch on both Th1 and Th2 responses, which may have important implications for vaccination against hepatitis B virus, as well as for enhancing weak immunogenicity of other recombinant purified antigens in a nonresponder population.
 ...
PMID:Cationic lipid DC-Chol induces an improved and balanced immunity able to overcome the unresponsiveness to the hepatitis B vaccine. 1036 54

The standard hepatitis B surface Ag (HBsAg) vaccine fails to induce anti-hepatitis B surface Abs in 5-10% of healthy subjects, a phenomenon known as HBsAg nonresponsiveness, which is closely related to HLA class II alleles and impaired Th cell responses to HBsAg in these subjects. We hypothesized that GM-CSF, a potent adjuvant in enhancing the Ag-presentation activity of APCs, might help to generate Th cell responses in nonresponders, subsequently providing help for B cells to produce anti-hepatitis B surface Abs. We used a thermosensitive biodegradable copolymer (hydrogel) system to codeliver HBsAg and GM-CSF to achieve maximal local cytokine activity at the injection site. In responder mouse strains, hydrogel-formulated HBsAg plus GM-CSF (Gel/HBs+GM) vaccine elicited much greater anti-hepatitis B surface Ab titers and Th cell proliferative responses than a commercial aluminum-formulated HBsAg vaccine or free HBsAg. The adjuvant effect of the Gel/HBs+GM vaccine was dependent upon the local release of GM-CSF. More importantly, the Gel/HBs+GM vaccine elicited high HBsAg-specific Ab titers and Th cell responses in B10.M mice, a mouse strain that does not respond to the current HBsAg vaccine because of its H-2 haplotype. Analysis of the draining lymph nodes of Gel/HBs+GM vaccine-treated mice revealed an elevated number of CD11c(+) dendritic cells showing enhanced expression of MHC class II and a variety of costimulatory molecules. These results demonstrate that hydrogel-formulated GM-CSF might represent a simple and effective method to generate next-generation hepatitis B virus vaccines for inducing anti-hepatitis B surface Abs in nonresponders.
 ...
PMID:Hydrogel-delivered GM-CSF overcomes nonresponsiveness to hepatitis B vaccine through the recruitment and activation of dendritic cells. 2088 41

Hepatitis B can be effectively prevented by hepatitis B vaccination. However, hyporesponse to the hepatitis B vaccine has been found in both human and inbred mice with particular MHC alleles or haplotypes, but the mechanisms underlying this poor response remains elusive. In the present study, we investigated the mechanisms underlying the hyporesponse to hepatitis B vaccination using B10.S-H2s/SgMcdJ (B10.S, H-2(s), poor responder) and C57BL/10J (B10, H-2(b), good responder) mice. We observed that the B10.S mice displayed a hyporesponse to HBsAg vaccine but a normal response to 3 other foreign antigens (influenza A (H1N1) 2009 monovalent vaccine, tetanus toxoid and ovalbumin). In B10.S mice immunized with HBsAg, the levels of serum anti-HBs IgG, the number of HBsAg-specific IgG-secreting plasma cells and HBsAg-specific Th cells were considerably lower than that in B10 mice. Further, the findings of the insufficient maturation (CD86), co-stimulation (CD40) and migration (CCR7) activities of DCs together with the inadequate activation of the HBsAg-specific Th cells by APCs were identified as part of the reason for the HBsAg hyporesponse in B10.S mice, which supports the hypothesis that measures aimed at promoting the maturation, co-stimulation or migration of APCs to enhance Th cell activation may be a useful strategy for the development of new hepatitis B vaccines.
...
PMID:Inadequate activation of the HBsAg-specific Th cells by APCs leads to hyporesponsiveness to HBsAg vaccine in B10.S mice. 2608 3

Entry inhibitors are promising novel antivirals against hepatitis B virus (HBV) infection. The existing potential entry inhibitors have targeted the cellular receptor(s). In this study, we aim to develop the first entry inhibitor that inhibits HBV infection via targeting viral particles. The preS1 segment of the large envelope glycoprotein of HBV is essential for virion attachment and infection. Previously, we obtained a preS1-binding short peptide B10 by screening a phage display peptide library using the N-terminal half of preS1 (residues 1 to 60, genotype C). We report here that by means of concatenation of B10, we identified a quadruple concatemer 4B10 that displayed a markedly increased preS1-binding activity. The main binding site of 4B10 in preS1 was mapped to the receptor binding enhancing region. 4B10 blocked HBV attachment to hepatic cells and inhibited HBV infection of primary human and tupaia hepatocytes at low nanomolar concentrations. The 4B10-mediated inhibition of HBV infection is specific as it did not inhibit the infection of vesicular stomatitis virus glycoprotein pseudotyped lentivirus or human immunodeficiency virus type 1. Moreover, 4B10 showed no binding activity to hepatic cells. In conclusion, we have identified 4B10 as a promising candidate for a novel class of HBV entry inhibitors.
 ...
PMID:Efficient Inhibition of Hepatitis B Virus Infection by a preS1-binding Peptide. 2738 14


<< Previous 1 2 3 Next >>