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)

We engineered a multiepitope DNA minigene encoding nine dominant HLA-A2.1- and A11-restricted epitopes from the polymerase, envelope, and core proteins of hepatitis B virus and HIV, together with the PADRE (pan-DR epitope) universal Th cell epitope and an endoplasmic reticulum-translocating signal sequence. Immunization of HLA transgenic mice with this construct resulted in: 1) simultaneous CTL induction against all nine CTL epitopes despite their varying MHC binding affinities; 2) CTL responses that were equivalent in magnitude to those induced against a lipopeptide known be immunogenic in humans; 3) induction of memory CTLs up to 4 mo after a single DNA injection; 4) higher epitope-specific CTL responses than immunization with DNA encoding whole protein; and 5) a correlation between the immunogenicity of DNA-encoded epitopes in vivo and the in vitro responses of specific CTL lines against minigene DNA-transfected target cells. Examination of potential variables in minigene construct design revealed that removal of the PADRE Th cell epitope or the signal sequence, and changing the position of selected epitopes, affected the magnitude and frequency of CTL responses. Our results demonstrate the simultaneous induction of broad CTL responses in vivo against multiple dominant HLA-restricted epitopes using a minigene DNA vaccine and underline the utility of HLA transgenic mice in development and optimization of vaccine constructs for human use.
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PMID:Utilization of MHC class I transgenic mice for development of minigene DNA vaccines encoding multiple HLA-restricted CTL epitopes. 1020 10

Recently we generated a panel of hepatitis B virus core gene mutants carrying single insertions or deletions which allowed efficient expression of the core protein in bacteria and self-assembly of capsids. Eleven of these mutations were introduced into a eukaryotic core gene expression vector and characterized by trans complementation of a core-negative HBV genome in cotransfected human hepatoma HuH7 cells. Surprisingly, four mutants (two insertions [EFGA downstream of A11 and LDTASALYR downstream of R39] and two deletions [Y38-R39-E40 and L42]) produced no detectable capsids. The other seven mutants supported capsid formation and pregenome packaging/viral minus- and plus-strand-DNA synthesis but to different levels. Four of these seven mutants (two insertions [GA downstream of A11 and EHCSP downstream of P50] and two deletions [S44 and A80]) allowed virion morphogenesis and secretion. The mutant carrying a deletion of A80 at the tip of the spike protruding from the capsid was hepatitis B virus core antigen negative but wild type with respect to virion formation, indicating that this site might not be crucial for capsid-surface protein interactions during morphogenesis. The other three nucleocapsid-forming mutants (one insertion [LS downstream of S141] and two deletions [T12 and P134]) were strongly blocked in virion formation. The corresponding sites are located in the part of the protein forming the body of the capsid and not in the spike. These mutations may alter sites on the particle which contact surface proteins during envelopment, or they may block the appearance of a signal for the transport or the maturation of the capsid which is linked to viral DNA synthesis and required for envelopment.
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PMID:Hepatitis B virus core gene mutations which block nucleocapsid envelopment. 1059 84

The hepatitis B vaccine is considered to be highly immunogenic and has a good safety profile. In adults, it has a primary non-response rate of 5%-10%. Causes of nonresponse to hepatitis B vaccine include age, sex, obesity smoking. Certain human leucocyte antigen (HLA) phenotypes have been known to be associated with responsiveness to the vaccine, and found to be different in different ethnic groups, such as Caucasians and Orientals. The study was designed to identify the HLA phenotypes that are associated with non-responsiveness to hepatitis B virus (HBV) vaccination amongst a cohort of Indian subjects who agreed to participate in the vaccination programme. The study was offered to 107 volunteers, of whom 102 were found to be negative for HBV markers (hepatitis B surface antigen [HBsAg], anti-HBc, anti-HBe, anti-HBs, hepatitis Be antigen [HBeAg]) . All 102 volunteers were offered recombinant hepatitis B vaccine (20 microg) at 0, 1, and 6 months. Anti-HBs antibody titres were tested on days 90 and 210 of the first vaccine dose. HLA typing was done using standard microlymphotoxicity tests. The seroconversion rate of the hepatitis B vaccine was 86.3% (88/102). Fifteen nonresponders (15/102) and 15 of the 88 responders were randomly selected after age and sex matching for the purpose of studying the HLA phenotypes. HLA subtypes A1, B15, B40, A10 and DQ2 were found to be increased among nonresponders while HLA- A11, C3, DR10, DR51 (p>0.05) were the most common phenotypes amongst the responders. Further studies are needed to characterize the HLA phenotypes amongst the responders in different ethnic groups in India with respect to HBV vaccination.
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PMID:Association of HLA phenotype with primary non-response to recombinant hepatitis B vaccine: a study from north India. 1568 56

HLA class I (HLA-I) transgenic mice have proven to be useful models for studying human MHC-related immune responses over the last two decades. However, differences in the processing and presentation machinery between humans and mice may have profound effects on HLA-I restricted antigen presentation. In this study, we generated a novel human TAP-LMP (hTAP-LMP) gene cluster transgenic mouse model carrying an intact human TAP complex and two human immunoproteasome LMP subunits, PSMB8/PSMB9. By crossing the hTAP-LMP strain with different HLA-I transgenic mice, we found that the expression levels of human HLA-I molecules, especially the A3 supertype members (e.g., A11 and A33), were remarkably enhanced in corresponding HLA-I/hTAP-LMP transgenic mice. Moreover, we found that humanized processing and presentation machinery increased antigen presentation of HLA-A11-restricted epitopes and promoted the rapid reduction of hepatitis B virus (HBV) infection in HLA-A11/hTAP-LMP mice. Together, our study highlights that HLA-I/hTAP-LMP mice are an improved model for studying antigen presentation of HLA-I molecules and their related CTL responses.
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PMID:Improved Transgenic Mouse Model for Studying HLA Class I Antigen Presentation. 2763 83