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

Size of the polymeric particulate antigen delivery system and its interactions with antigen-presenting cells (APCs) influence the immune response both qualitatively and quantitatively. In this paper, we report that antigen-loaded polymeric microparticles elicit antibody titers without being phagocytosed by macrophages; and size of the antigen-loaded particles modulates immune response from single-point immunization. Antibody titers varied significantly from single-point immunization with different sized polylactide (PLA) particles entrapping hepatitis B surface antigen. Nanoparticles (200-600 nm) were efficiently taken up by macrophages and elicited lower antibody titers in comparison to microparticles (2-8 microm). PLA microparticles that elicited highest and long-lasting antibody titers from single-point immunization were not taken up by the macrophages and found attached to the surface of the macrophages. Immunization with nanoparticles (200-600 nm) was associated with higher levels of IFN-gamma production, upregulation of MHC class I molecules along with antibody isotypes favoring Th1-type immune response. Immunization with microparticles (2-8 microm size) promoted IL-4 secretion, upregulated MHC class II molecules and favored Th2-type immune response. Western blot analysis showed that release of HBsAg from surface-attached microparticles into macrophages increased with time, but was more or less constant in case of nanoparticles. Our results suggest that continuous release of high concentration of antigen from cell surface-attached PLA microparticles into APCs results in improved antibody response from single-point immunization. It also offers an exciting possibility of designing size-based polymer particle delivery system to modulate immune response.
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PMID:Interactions of antigen-loaded polylactide particles with macrophages and their correlation with the immune response. 1782 5

Immunopathogenesis of chronic viral hepatitides was studied by modern immunological, molecular, genetic methods. We revealed an imbalance in the production of immunoregulatory cytokines by mononuclear leukocytes (primarily of the Th2 type). The risk of progression and chronic course of viral hepatitides in Caucasian population was associated with alleles of promoter regions -330G and -592A in the IL-2 and IL-10 genes, respectively, as well as with the T/T genotype of the polymorphic region C590T in the IL-4 gene. The C/C genotype of the IL-10 gene promoter region C592A was shown to be a factor determining resistance to long-term persistence of hepatitis B and C viruses.
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PMID:Role of genetically determined production of immunoregulatory cytokines in immunopathogenesis of chronic viral hepatitides. 1823 7

An emerging paradigm in vaccinology is that multiple adjuvant combinations may be more effective than individual adjuvants in enhancing immune responses to vaccine antigens. We investigated whether the polyphosphazenes used in combination with CpG oligodeoxynucleotides (ODN) were potent adjuvant formulations. BALB/c mice were immunized subcutaneously with Hepatitis B surface antigen (HBsAg) alone, or in various combinations with poly[di(sodium carboxylatophenoxy)phosphazene] (PCPP), poly[di(sodium carboxylatoethylphenoxy)phosphazene] (PCEP) or CpG ODN. All three adjuvants enhanced HBsAg-specific IgG1 antibody responses with PCEP inducing the highest responses. PCEP and CpG ODN significantly enhanced the Th1-associated antibody isotype IgG2a. As expected CpG ODN induced predominantly Th1-type immune responses while PCEP was associated with mixed Th1/Th2 immune responses. Interestingly, PCEP and PCPP synergized with CpG ODN to further enhance antibody responses. Since the mechanisms which mediate the adjuvant activity of polyphosphazenes are not fully understood, we investigated whether PCEP and PCPP could stimulate innate immune responses. Incubation of mouse splenocytes with PCEP or PCPP (in the absence of antigen) stimulated production of IL-4 and IL-12, but only PCEP induced significant IFNgamma production. Additionally, IL-12 was not required for PCEP induced IFNgamma response. We conclude that the polyphosphazene-CpG ODN combination is a potent adjuvant formulation that is more effective in enhancing immune responses than either of the individual adjuvants. In addition, we provide evidence that PCEP and PCPP can stimulate innate cytokine production, suggesting a potential mechanism by which polyphosphazenes achieve their potent adjuvant effects.
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PMID:Co-administration of polyphosphazenes with CpG oligodeoxynucleotides strongly enhances immune responses in mice immunized with Hepatitis B virus surface antigen. 1843 Apr 93

Cimetidine (CIM), a histamine 2-receptor antagonist, is postulated to enhance immune responses owing to its inhibitory effects on suppressor T cells. In this report, we evaluated effects of cimetidine on the potency of antigen-specific immunity generated by DNA vaccine encoding hepatitis B surface antigen (HBsAg, pcD-S2). Our data demonstrate that CIM as adjuvant significantly increased HBsAg-specific cell-mediated and humoral immunities that were characterized by higher Ig2a/IgG1 ratio. In addition, CIM significantly promotes an elevated level of IL-4 and IFN-gamma in antigen-specific CD4(+) T cells and a robust antigen-specific cytotoxic response in the animals immunized with pcD-S2 plus CIM. Further, CIM induces pro-inflammatory cytokine expression such as the IL-12 and down-regulates anti-inflammatory cytokine expression such as IL-10 and TGF-beta, which may lead to an impairment of CD4(+)CD25(+) Treg cell-mediated suppression. Collectively these findings suggest that CIM enhances the immune responses of HBV DNA vaccine through the stimulation of pro-inflammatory and inhibition of anti-inflammatory cytokine expression patterns.
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PMID:Cimetidine enhances immune response of HBV DNA vaccination via impairment of the regulatory function of regulatory T cells. 1850 98

High prevalence of hepatitis B virus (HBV) infection in China offers a unique setting to examine HBV's influence on the presentation of dengue fever. In 398 patients admitted for suspected dengue fever, 89% (353/398) were positive for dengue IgM antibodies. Among dengue-infected patients, 8% (29/353) had chronic HBV co-infection. Only dengue virus serotype 1 was identified by virus isolation and reverse transcriptase-polymerase chain reaction assays. No case of dengue hemorrhagic fever/dengue shock syndrome was diagnosed. In addition to routine clinical tests, interleukin 2 (IL-2), IL-4, IL-6, IL-10, interferon gamma (IFNgamma), and tumor necrosis factor alpha (TNFalpha) levels were measured in the sera of 95% (334/353) of dengue-infected subjects as well as controls. Surprisingly, HBV/dengue co-infected patients made less IL-6 (P < 0.05) and TNFalpha (P < 0.05) than patients with only dengue infection. Similar levels of IL-4, IL-10, and IFNgamma were found in both groups. Thus, HBV co-infection seems to alter the cytokine production pattern when patients contract dengue infection.
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PMID:Unique impacts of HBV co-infection on clinical and laboratory findings in a recent dengue outbreak in China. 1868 15

We recently described a delivery system that is composed of a chitosan core to which the hepatitis B surface antigen (HBsAg) was adsorbed and subsequently coated with sodium alginate. In this present work, alginate coated chitosan nanoparticles were evaluated as a subcutaneous adjuvant for HBsAg. HBsAg loaded, alginate coated or uncoated chitosan nanoparticles, associated or not with CpGODN were subcutaneously administered to mice and several immunological parameters were evaluated. A high anti-HBsAg IgG titer (2271+/-120 mIU/ml), with the majority of antibodies being of Th2 type, was observed within group I, vaccinated with HBsAg loaded onto coated nanoparticles. However, regarding cellular immune response, no significant differences were observed for antigen-specific splenocyte proliferation or for the secretion of IFN-gamma and IL-4, when compared to the control group. The co-delivery of antigen-loaded nanoparticles in the presence of the immunopotentiator, CpG ODN 1826, resulted in an increase of anti-HBsAg IgG titers that was not statistically different from the first group; however, an increase of the IgG2a/IgG1 ratio from 0.1 to 1.0 and an increase (p<0.01) of the IFN-gamma production by the splenocytes stimulated with the HBV antigen was observed. The enhancement of the immune response observed with the antigen-loaded nanoparticles demonstrated that chitosan is a promising platform for parenteral HBsAg delivery and, when co-administered with the CpG ODN, resulted in a mixed Th1/Th2 type immune response.
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PMID:Alginate coated chitosan nanoparticles are an effective subcutaneous adjuvant for hepatitis B surface antigen. 1880 62

Currently, there is a clinical need for more effective vaccine for hepatitis B that induces robust cell-mediated immune response capable of viral clearance in chronic hepatitis B infection. In the present study, hepatitis B vaccines formulations were designed by loading the hepatitis B surface antigen into liposomes adjuvanted with rough lipopolysaccharide (Re-LPS) and lpxL1 LPS using conventional rotatory evaporation method and were characterized for various parameters, such as vesicle shape and surface morphology, size and size distribution, entrapment efficiency, turbidity, and in vitro release pattern. The immunoreactivity in mice was evaluated by measuring anti-HBs IgG titer and compared with alum-adsorbed HBsAg solution, plain HBsAg, and liposomal HBsAg formulations. The formulations were also evaluated for cell-mediated immune response by HBsAg specific proliferation of spleenocytes after secondary immunization and re-stimulation in vitro with the same antigen. Simultaneous estimation of cytokines (IL-4, IFN-gamma) was also carried out. Ex vivo cellular uptake study was performed by fluorescence microscopy. Results indicate that the serum IgG titer obtained after i.m administration of Re-LPS- and lpxL1 LPS-adjuvanted liposomal HBsAg formulation was equivalent to alum-adsorbed HBsAg formulation but was more responsive, sustained, and significantly higher than the corresponding liposomal HBsAg and plain HBsAg formulations. Incorporation of lpxL1 LPS into the liposomal HBsAg increased the stimulation index (SI) 6-10 times as compared with plain HBsAg. Re-LPS- and lpxL1 LPS-adjuvanted liposomal HBsAg formulations induced stronger cellular immune response with a predominant Interferon-gamma (IFN-gamma) level than those induced by free HBsAg alone, alum-adsorbed HBsAg, and non-adjuvanted liposomal HBsAg. Probably, the possible mechanism for the enhancement of cellular immunity in addition to humoral immunity by LPS-adjuvanted liposomal HBsAg formulation is due to marked enhancement of immunological presentation and recruitment of antigen via macrophage and antigen-presenting cells (APCs).
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PMID:Enhancement of T-helper type I immune responses against hepatitis B surface antigen by LPS derivatives adjuvanted liposomes delivery system. 1898 19

Chronic hepatitis B virus infection is characterized by persistent detectable levels of hepatitis B surface antigen (HBsAg) and HBV DNA in the serum. In contrast, HBsAg is not detectable during occult HBV infection, despite the presence of HBV DNA. An altered host immune response could play a role in the development of occult HBV infection; however, potential differences in immune responses among chronic and occult HBV-infected patients have not been evaluated in vivo. In the current study, we evaluated serum levels of regulatory, apoptotic, and fibrotic/anti-fibrotic cytokines/markers as indicators of immune responses in 25 chronic and 12 occult HBV-infected patients. More than half of the patients in both chronic and occult HBV infection groups had IL-2, IL-4, IL-13, and IFN-gamma levels below detectable limits. In contrast, most patients had detectable levels of IL-8, IL-10, IP-10, sFas, sFasL, and TGF-beta1. Of these, only sFas was significantly different between the two groups, with lower levels observed during occult compared to chronic HBV infection (p=0.01). As a surrogate marker of apoptotic inhibition, decreased sFas during occult HBV infection suggests that apoptosis occurs at different rates in occult compared to chronic HBV infection and therefore, may contribute to persistence of occult HBV infection.
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PMID:Cytokine expression during chronic versus occult hepatitis B virus infection in HIV co-infected individuals. 1962 94

Recent studies have suggested that yeast cell wall components possess adjuvant activities. In the present study, heat-killed whole recombinant Hansenula polymorpha yeast expressing hepatitis B surface antigen (yeast-HBsAg) was generated, and the immune responses elicited by yeast-HBsAg were investigated in mice. The studies showed that yeast-HBsAg as well as yeast greatly promotes the accumulation of immune cells in mouse spleen and contributes to the maturation of dendritic cells (DCs). Yeast-HBsAg not only induces significantly higher antibody responses (including IgG, IgG1 and IgG2a), but also increases the IgG2a/IgG1 ratio, while alum combined with HBsAg (HBsAg+alum) only enhances antibody responses, but not the IgG2a/IgG1 ratio compared to HBsAg alone. Analysis of HBsAg-specific cytokines revealed that yeast-HBsAg is associated with production of both IFN-gamma and IL-4, but neither IFN-gamma nor IL-4 was detected in the HBsAg+alum-immunized group. Moreover, yeast-HBsAg induces potent HBsAg-specific lymphocyte proliferation and Cytotoxic T lymphocyte (CTL) responses. In conclusion, yeast-HBsAg enhances both HBsAg-specific Th1 and Th2 immune responses, while alum only enhances Th2 immune responses, suggesting that yeast-HBsAg may be an ideal candidate for an effective vaccine for the control of chronic hepatitis B virus (HBV) infection.
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PMID:Whole recombinant Hansenula polymorpha expressing hepatitis B virus surface antigen (yeast-HBsAg) induces potent HBsAg-specific Th1 and Th2 immune responses. 1978 93

The magnitude of the immune response to vaccinations can be influenced by genetic variability. In the present study, we aimed to investigate whether cytokine or cytokine receptor gene polymorphisms were associated with variations in the immune response to childhood vaccination. The study group consisted of 141 healthy infants who had been immunized with hepatitis B vaccine (HBV), 7-valent pneumococcal conjugate (PCV7), and diphtheria, tetanus, acellular pertussis (DTaP) vaccines according to standard childhood immunization schedules. Genotype analysis was performed on genomic DNA using a 5' nuclease PCR assay. Post vaccination total, isotypic, and antigen-specific serum antibody levels were measured using multiplex immunoassays. Significant associations were observed between SNPs in the TNFalpha, IL-12B, IL-4Ralpha, and IL-10 genes and vaccine-specific immune responses (p<0.05). In addition, SNPs in the IL-1beta, TNFalpha, IL-2, IL-4, IL-10, IL-4Ralpha, and IL-12B genes were associated with variations in serum levels of immunoglobulins (IgG, IgA, IgM) and IgG isotypes (IgG1-IgG3) (p<0.05). These data suggest that genetic variations in cytokine genes can influence vaccine-induced immune responses in infants, which in turn may influence vaccine efficacy.
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PMID:Influence of cytokine gene variations on immunization to childhood vaccines. 1981 9


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