scholarly journals Genetic regulation of the immune response to hepatitis B surface antigen (HBsAg). IV. Distinct H-2-linked Ir genes control antibody responses to different HBsAg determinants on the same molecule and map to the I-A and I-C subregions.

1984 ◽  
Vol 159 (1) ◽  
pp. 41-56 ◽  
Author(s):  
D R Milich ◽  
G G Leroux-Roels ◽  
R E Louie ◽  
F V Chisari
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Hepatitis B ◽  
Immune Responses ◽  
Surface Antigen ◽  
Antibody Production ◽  
Hepatitis B Surface Antigen ◽  
Antigenic Determinants ◽  
Ir Genes

We have previously demonstrated that the murine humoral immune responses to the group-specific a and subtype-specific d/y determinants of hepatitis B surface antigen (HBsAg) are controlled by H-2-linked immune response (Ir) genes. High responder (H-2d,q), intermediate responder (H-2a greater than b greater than k) and nonresponder (H-2f,s) haplotypes have been identified (8, 9). The kinetics and specificity of in vivo antibody production after HBsAg immunization in congeneic, H-2-recombinant strains was analyzed to further define relevant Ir genes and their influence on the immune response to distinct antigenic determinants. These studies indicate that the humoral anti-HBs response is regulated by at least two Ir genes, one in the I-A subregion (Ir-HBs-1) and one in the I-C subregion (Ir-HBs-2) of the murine H-2 complex. Ir-HBs-1 regulates the primary responses to all HBsAg determinants, whereas the influence of Ir-HBs-2 is determinant specific, affecting the responses to the d or y determinants. The anti-a response is regulated exclusively by Ir-HBs-1. Strains possessing only the Ir-HBs-2 gene [B10.S(9R) and B10.HTT] produce no anti-a response and a subtype-specific antibody response is detected only after secondary or tertiary immunization. In contrast, the influence of Ir-HBs-2 in the presence of Ir-HBs-1 is detected upon primary immunization and is additive rather than exclusive. There is also suggestive evidence that the presence of the Ek molecule, at least in the context of I-Ak, may have a suppressive influence on the anti-HBs response. Additionally, HBsAg-specific, T cell proliferative responses were H-2 restricted and the kinetics and specificity of T cell proliferative responses paralleled in vivo antibody production. These data indicate that, although the I-A subregion exerts a dominant influence, distinct Ir-HBs genes, mapping in separate I subregions, control immune responses to alternate HBsAg determinants on the same protein molecule.

scholarly journals Mimicry of the a determinant of hepatitis B surface antigen by an antiidiotypic antibody. I. Evaluation in hepatitis B surface antigen responder and nonresponder strains.

1993 ◽  
Vol 177 (1) ◽  
pp. 127-134 ◽  
Author(s):  
M W Pride ◽  
A Thakur ◽  
Y Thanavala
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Lymph Node ◽  
T Cell ◽  
Hepatitis B ◽  
Surface Antigen ◽  
Hepatitis B Surface Antigen ◽  
T Cell Response

B and T cell responses of several strains of mice, immunized with a monoclonal antiidiotype (anti-Id) that mimics the a determinant of hepatitis B surface antigen (HBsAg), were studied to determine if the immune response to the anti-Id was regulated by H-2-linked immune response genes as has been previously observed for HBsAg. We report that immunization with anti-Id could elicit HBsAg-specific antibodies in mice of the H-2d,q, or f haplotype and in an outbred wild mouse strain (Mus spretus), thus circumventing the H-2 haplotype restriction pattern observed when immunizing with HBsAg in H-2f mice. Purified lymph node T cells from mice of the H-2d or q haplotype and M. spretus that were primed in vivo with HBsAg or anti-Id could be stimulated in vitro with either HBsAg or anti-Id but not with an irrelevant antibody of the same subclass as the anti-Id. However, purified lymph node T cells from H-2f mice that were primed in vivo with the anti-Id could only be stimulated in vitro with anti-Id. No in vitro stimulation whatsoever was observed in H-2f mice immunized with HBsAg. The effect of processing and presentation of the anti-Id by antigen-presenting cells (APC) was studied in mice of the H-2d haplotype. Stimulation of purified lymph node T cells by HBsAg and anti-Id was shown to be strictly dependent on APC and restricted by major histocompatibility complex class II antigens at the I-A locus. Treatment of APC with paraformaldehyde or chloroquine abrogated the T cell response to all antigens except for a nine-amino acid synthetic peptide representing a partial analogue of the group a determinant of HBsAg S(139-147). The significance of these results is discussed in the context of understanding the mechanism of mimicry elicited by the anti-Id.

scholarly journals Enhancement of the immune response to hepatitis B surface antigen. In vivo administration of antiidiotype induces anti-HBs that expresses a similar idiotype.

1984 ◽  
Vol 159 (3) ◽  
pp. 655-665 ◽  
Author(s):  
R C Kennedy ◽  
G R Dreesman
Keyword(s):  
Immune Response ◽  
Hepatitis B ◽  
Surface Antigen ◽  
Hepatitis B Surface Antigen ◽  
Soluble Form ◽  
Viral Agent ◽  
Data Support ◽  
In Vivo Administration ◽  
Specific Determinant

BALB/c mice receiving antiidiotype antibodies before the injection of hepatitis B surface antigen (HBsAg) generated an enhanced anti-HBs response. Mice given antiidiotype antibodies in a soluble form induced predominantly IgM anti-HBs, whereas alum-precipitated antiidiotype produced primarily IgG anti-HBs. Injection of antiidiotype antibodies alone induced anti-HBs that inhibited a common interspecies anti-HBs idiotype-antiidiotype reaction and recognized the group-specific determinant of HBsAg. These data support the view that antiidiotype antibodies may modulate the immune response to an infectious viral agent.

scholarly journals Evaluation of Solid Lipid Nanoparticles as Carriers for Delivery of Hepatitis B Surface Antigen for Vaccination Using Subcutaneous Route

2010 ◽  
Vol 13 (4) ◽  
pp. 495 ◽  
Author(s):  
Dinesh Mishra ◽  
Himanshu Mishra ◽  
Pradyumna K. Mishra ◽  
Manoj Nahar ◽  
Vaibhav Dubey ◽  
...  
Keyword(s):  
Immune Response ◽  
Hepatitis B ◽  
Cellular Uptake ◽  
Surface Antigen ◽  
Solid Lipid Nanoparticles ◽  
Hepatitis B Surface Antigen ◽  
Lipid Nanoparticles ◽  
Subcutaneous Route

Purpose: Solid lipid nanoparticles (SLN) have emerged as carriers for therapeutic peptides, proteins, antigens and bioactive molecules. We have explored the potential of SLN as carrier for Hepatitis B surface antigen (HBsAg) by surface modifications to enhance their loading efficiency and the cellular uptake, using subcutaneous route. Methods: Four different formulations of SLN were prepared by solvent injection method and characterized for various physical properties: particle size, surface morphology, shape, zeta potential, polydispersity, X-ray diffraction analysis, release profile and entrapment efficiency. HBsAg loaded SLN were studied for their functional characteristics, in vitro cellular uptake and internalization studies by human dendritic cells, macrophages and fibroblasts, T cell proliferation and TH1/TH2 response. Humoral immune response elicited by subcutaneously administered HBsAg containing SLN formulations were studied in vivo in mice. Results: Compared to soluble HBsAg; SLN, particularly the mannosylated formulation, showed better cellular uptake, lesser cytotoxicity and induction of greater TH1 type of immune response. They also showed better immunological potential by producing sustained antibody titer. Conclusion: Mannosylated SLN appears to be promising as carrier for vaccine delivery against hepatitis B as ascertained by in vitro and in vivo studies, however further investigations on humans are required to establish their potential as vaccines against hepatitis B infection.

scholarly journals Targeting Murine Immune Responses to Selected T Cell- or Antibody-Defined Determinants of the Hepatitis B Surface Antigen by Plasmid DNA Vaccines Encoding Chimeric Antigen

2001 ◽  
Vol 166 (2) ◽  
pp. 1405-1413 ◽  
Author(s):  
Reinhold Schirmbeck ◽  
Xin Zheng ◽  
Michael Roggendorf ◽  
Michael Geissler ◽  
Francis V. Chisari ◽  
...  
Keyword(s):  
T Cell ◽  
Hepatitis B ◽  
Immune Responses ◽  
Surface Antigen ◽  
Plasmid Dna ◽  
Dna Vaccines ◽  
Hepatitis B Surface Antigen

How Far we are towards Eradication of HBV Infection

2015 ◽  
Vol 24 (4) ◽  
pp. 473-479 ◽  
Author(s):  
Mihai Voiculescu
Keyword(s):  
Immune Response ◽  
Hepatitis B Virus ◽  
T Cell ◽  
Hepatitis B ◽  
T Cell Receptors ◽  
Hepatitis B Surface Antigen ◽  
Hbv Infection ◽  
Major Health Problem ◽  
Cell Receptors ◽  
B Virus

Hepatitis B virus (HBV) infection is a major health problem with an important biological and a significant socio-economic impact all over the world. There is a high pressure to come up with a new and more efficient strategy against HBV infection, especially after the recent success of HCV treatment. Preventing HBV infection through vaccine is currently the most efficient way to decrease HBV-related cirrhosis and liver cancer incidence, as well as the best way to suppress the HBV reservoir. The vaccine is safe and efficient in 80-95% of cases. One of its most important roles is to reduce materno-fetal transmission, by giving the first dose of vaccine in the first 24 hours after birth. Transmission of HBV infection early in life is still frequent, especially in countries with high endemicity.Successful HBV clearance by the host is immune-mediated, with a complex combined innate and adaptive cellular and humoral immune response. Different factors, such as the quantity and the sequence of HBV epitope during processing by dendritic cells and presenting by different HLA molecules or the polymorphism of T cell receptors (TOL) are part of a complex network which influences the final response. A new potential therapeutic strategy is to restore T-cell antiviral function and to improve innate and adaptive immune response by immunotherapeutic manipulation.It appears that HBV eradication is far from being completed in the next decades, and a new strategy against HBV infection must be considered. Abbreviations: ALT: alanine aminotransferase; APC: antigen presenting cells; cccDNA: covalently closed circular DNA; HBIG: hepatitis B immunoglobulin; HbsAg: hepatitis B surface antigen; HBV: hepatitis B virus; HCC: hepatocellular carcinoma; CTL: cytotoxic T lymphocyte; IFN: interferon; NUC: nucleos(t)ide analogues; pg RNA: pre genomic RNA; TLR: toll-like receptors; TOL: T cell receptors.

Synthesis of hepatitis B surface antigen pre-S2 region fragments and studies on their immunogenicity

1988 ◽  
Vol 53 (11) ◽  
pp. 2952-2956 ◽  
Author(s):  
Bernard Lammek ◽  
Zbigniew Maćkiewicz ◽  
Izabela Derdowska ◽  
Hanna Świderska ◽  
Adam Nowosławski ◽  
...  
Keyword(s):  
Hepatitis B ◽  
Surface Antigen ◽  
Solid Phase ◽  
Hepatitis B Surface Antigen ◽  
Gel Filtration ◽  
Exchange Chromatography ◽  
Antigenic Determinants ◽  
Phase Method ◽  
Peptide Fragments ◽  
Humoral Immune

Two peptide fragments of hepatitis B surface antigen pre-S2 region were synthesized by the solid phase method. The peptides were purified by gel filtration or ion-exchange chromatography on Sephadex SP-C-25. Both peptides induced a cellular and humoral immune response in rabbits. The results showed that fragment 14-22 of pre-S2 region contains one of the antigenic determinants.

scholarly journals Optimized Adenovirus-Antibody Complexes Stimulate Strong Cellular and Humoral Immune Responses against an Encoded Antigen in Naïve Mice and Those with Preexisting Immunity

2011 ◽  
Vol 19 (1) ◽  
pp. 84-95 ◽  
Author(s):  
Jin Huk Choi ◽  
Joe Dekker ◽  
Stephen C. Schafer ◽  
Jobby John ◽  
Craig E. Whitfill ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Immune Responses ◽  
Neutralizing Antibodies ◽  
T Cell Responses ◽  
Transduction Efficiency ◽  
Virus Antibody ◽  
Cell Responses

ABSTRACTThe immune response to recombinant adenoviruses is the most significant impediment to their clinical use for immunization. We test the hypothesis that specific virus-antibody combinations dictate the type of immune response generated against the adenovirus and its transgene cassette under certain physiological conditions while minimizing vector-induced toxicity.In vitroandin vivoassays were used to characterize the transduction efficiency, the T and B cell responses to the encoded transgene, and the toxicity of 1 × 1011adenovirus particles mixed with different concentrations of neutralizing antibodies. Complexes formed at concentrations of 500 to 0.05 times the 50% neutralizing dose (ND50) elicited strong virus- and transgene-specific T cell responses. The 0.05-ND50formulation elicited measurable anti-transgene antibodies that were similar to those of virus alone (P= 0.07). This preparation also elicited very strong transgene-specific memory T cell responses (28.6 ± 5.2% proliferation versus 7.7 ± 1.4% for virus alone). Preexisting immunity significantly reduced all responses elicited by these formulations. Although lower concentrations (0.005 and 0.0005 ND50) of antibody did not improve cellular and humoral responses in naïve animals, they did promote strong cellular (0.005 ND50) and humoral (0.0005 ND50) responses in mice with preexisting immunity. Some virus-antibody complexes may improve the potency of adenovirus-based vaccines in naïve individuals, while others can sway the immune response in those with preexisting immunity. Additional studies with these and other virus-antibody ratios may be useful to predict and model the type of immune responses generated against a transgene in those with different levels of exposure to adenovirus.

scholarly journals Immune response by nasal delivery of hepatitis B surface antigen and codelivery of a CpG ODN in alginate coated chitosan nanoparticles

2008 ◽  
Vol 69 (2) ◽  
pp. 405-416 ◽  
Author(s):  
Olga Borges ◽  
Anabela Cordeiro-da-Silva ◽  
Joana Tavares ◽  
Nuno Santarém ◽  
Adriano de Sousa ◽  
...  
Keyword(s):  
Immune Response ◽  
Hepatitis B ◽  
Surface Antigen ◽  
Hepatitis B Surface Antigen ◽  
Chitosan Nanoparticles ◽  
Nasal Delivery ◽  
Cpg Odn
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