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)

Modified hepatitis B virus surface antigen M protein particles (HBsAg M-P31c) produced in yeast is mainly composed of two differently glycosylated proteins, GP37 and GP34. GP37 has an N-linked sugar chain and O-linked sugar chains; and GP34 has an N-linked sugar chain bound to the peptide backbone P31. Although M-P31c vaccine elicits both anti-S and anti-pre-S2 antibodies, whether there are any differences between GP37 and GP34 in the ability to elicit these antibodies is still unknown. To clarify this issue, we prepared particles which were composed solely of GP37 or GP34 by affinity chromatography, using polymerized human serum albumin as a ligand and digestion with alpha-mannosidase. We also prepared particles composed solely of P31 by successive digestion with alpha-manosidase and endo-beta-N-acetylglycosaminidase H. The vaccines derived from these three kinds of particles elicited both anti-S and anti-pre-S2 antibodies in mice to the same extent as the original M-P31c vaccine. These results suggest that the N- and O-linked sugar chains of M-P31c component proteins produced in the host yeast cells have no effect on the ability to elicit anti-S and anti-pre-S2 antibodies and that there are no differences with respect to antibody response in mice between the two major components of M-P31c, GP37 and GP34.
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PMID:Characterization of two differently glycosylated molecular species of yeast-derived hepatitis B vaccine carrying the pre-S2 region. 136 48

The pre-S2-coding region in the hepatitis B virus surface antigen M (P31; pre-S2 + S) protein gene was modified to identify a polymerized-albumin receptor (PAR) domain by deleting restriction fragments or performing site-directed mutagenesis. The modified M protein genes (M-P31x; x = d, e, f, h and i) were cloned into the yeast generalized-expression vector pGLD 906-1 and expressed in Saccharomyces cerevisiae under the control of yeast glyceraldehyde-3-phosphate dehydrogenase gene promoter. The PAR activities of these gene products suggested that the PAR domain is located in the hydrophilic and highly conserved domain in the pre-S2 region (around Leu12 approximately Tyr21). Antibodies specific for a pre-S2 peptide (Phe8 approximately Pro34, subtype adr), which covers the PAR domain, were purified from sera of rabbits immunized with yeast-derived M protein particles having a natural PAR domain. Immune electron microscopy showed that the purified antibodies could aggregate HBV particles. Therefore, it was speculated that the PAR domain overlapped with the dominant virus-neutralizing and virus-protecting epitopes.
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PMID:Identification of polymerized-albumin receptor domain in the pre-S2 region of hepatitis B virus surface antigen M protein. 136 62

The protective efficacy of a new type of yeast-derived hepatitis B (HB) vaccine (TGP-943, subtype adr), which was formulated from modified M (pre-S2 + S; P31) protein (M-P31c) particles, was investigated in chimpanzees. Animals were injected intramuscularly three times at 4-week intervals with doses of 10 or 40 micrograms (as a protein) of TGP-943. There were no significant differences in the immunogenicity of 10 micrograms compared to that of 40 micrograms of TGP-943 in terms of anti-S antibody response, while the induction and persistence of anti-pre-S2 antibodies seemed dose-related. Chimpanzees, vaccinated with 40 micrograms of TGP-943, produced anti-pre-S2 antibodies 2 weeks after the first injection, which appeared earlier than anti-HBs (S) antibodies. A maximum level of the anti-pre-S2 antibodies was reached 2 weeks after the second injection. Apart from immunization with TGP-943, chimpanzees injected with denatured TGP-943, consisting of 10 micrograms (as a protein) of non-particulate M-P31c antigen, produced anti-pre-S2 antibodies with a non-protecting level of anti-S antibodies (less than 10 mIU ml-1). Five weeks after the third injection, all animals were challenged intravenously with 1000 chimpanzee infectious units of HBV subtype (ayw) and were protected as confirmed by normal serological markers, no signs of infection in the sera and liver biopsies, and no detection of HBV-DNA by PCR method. No side effects from inoculation with TGP-943 or denatured TGP-943 were also encountered in any animals.
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PMID:Protective efficacy of a novel hepatitis B vaccine consisting of M (pre-S2 + S) protein particles (a third generation vaccine). 236 98

The hepatitis B virus surface antigen (HBsAg) P31 gene has been expressed in yeast Saccharomyces cerevisiae. The gene products were shown to be glycoproteins with molecular sizes of 37,000 and 34,000 daltons (GP37 and GP34) containing polymerized albumin receptors. Successfully detecting these proteins depended on the extraction procedures. In the extract without protein denaturants and inhibitors, these products were degraded rapidly by proteases to yield smaller size derivatives lacking polymerized albumin receptors. As is the case in human serum-derived HBsAg, yeast HBsAg consisting of GP37 and GP34 was found to be particles or aggregates having a buoyant density of 1.2 g/cc; these particles bound to polymerized human serum albumin in species-specific manner.
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PMID:Expression of hepatitis B virus surface antigen P31 gene in yeast. 242 75

Genetically modified M (pre-S2+S; P31) protein (M-P31c) particles were formulated into a vaccine (TGP-943) through adsorption on to an alum adjuvant. The immunogenicity of this vaccine was investigated using guinea-pigs and various kinds of mice. In terms of anti-HBs(S) response, TGP-943 was found to be as immunogenic as the control plasma-derived vaccine (PDV) and yeast-derived S vaccine (YDSV) in Balb/c mice. TGP-943 induced anti-S antibodies even in S low-responder mice. In addition to the anti-S antibodies, TGP-943 was shown to elicit anti-pre-S2 antibodies dose-dependently, and the anti-pre-S2 antibodies were maintained at a high level after immunization with a high dose of TGP-943. The antibody response to pre-S2 had a tendency to appear earlier than that to S. M-P31c particles induced in vitro proliferation of TGP-943-primed lymph node cells, indicating that TGP-943 is more immunogenic than conventional vaccines in terms of T-cell levels. These results suggest that TGP-943 would be a promising candidate for a third generation hepatitis B vaccine.
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PMID:Immunogenicity of a new type of yeast-derived hepatitis B vaccine consisting of M (pre-S2 + S) protein particles. 253 13

We have constructed plasmids that express modified hepatitis B virus surface antigen (HBsAg) P31-coding genes (M-P31c, d, e, f, and i) having various genetically engineered pre-S2 regions. The plasmids contain the GAPDH (gene coding for glyceraldehyde-3-phosphate dehydrogenase) promoter and the PGK (gene coding for 3-phosphoglycerate kinase) terminator, both isolated from sake brewing yeast, Saccharomyces cerevisiae Kyokai III. Expression levels of the modified HBsAg P31 proteins in yeast are greatly increased from 0.4% to 11.7% of total cell protein. However, the specific mRNAs are expressed at equal levels and the degradation rates of the modified P31 proteins do not vary significantly. Therefore, we considered that different expression levels of the modified P31 proteins are attributed to the changes of the post-translational efficiency. And it was suggested that the conformational stability of the N-terminal peptide (Met-1-Phe-46) in the endoplasmic reticulum membrane determines the expression level of modified P31 proteins.
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PMID:Efficient expression of genetically engineered hepatitis B virus surface antigen P31 proteins in yeast. 267 25

A hepatitis B virus surface antigen (HBsAg) P31-coding DNA was constructed from a DNA fragment of the plasmid pHBr330 containing the entire hepatitis B virus (HBV) adr DNA and a chemically synthesized adaptor. The P31 gene was inserted into an expression vector, pTRP771, having an Escherichia coli tryptophan operon (trp) promoter to give a recombinant plasmid pTRP P31-R. The distance between the Shine-Dalgarno (SD) sequence and the initiation codon of P31 gene was adjusted to 9 bp. The expression level of HBsAg by E. coli 294[pTRP P31-R] was significantly elevated, in contrast to that of HBsAg by E. coli 294[pTRP SS-6]. Western blotting analysis has shown that E. coli[pTRP P31-R] synthesizes a specific polypeptide P31 of about 31 kDal, which reacts with anti-HBsAg antibody. The binding studies with polyalbumins from various species have also suggested that HBsAg P31 specifically binds to polymerized human serum albumin.
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PMID:Expression of hepatitis B virus surface antigen P31 gene in Escherichia coli. 300 25

There are four polypeptides coded for by the region Pre-S and gene S on DNA of hepatitis B virus that carry the receptor for polymerized human serum albumin (poly-HSA), i.e., P31 and P39, as well as their glycosylated counterparts P35 and P43. With the use of monoclonal antibodies directed to Pre-S(1) sequence and Pre-S(2) sequence (bearing the receptor for poly-HSA), the content of these polypeptides, as well as their expression on the surface, was determined for hepatitis B particles of various categories. P39 and P43, carrying both Pre-S(1) and Pre-S(2) sequences, were contained abundantly in Dane and tubular particles, and to a much lesser extent in small spherical particles, all of which were purified from plasma containing hepatitis B e antigen (HBeAg). P31 and P35, carrying Pre-S(2) but not Pre-S(1) sequence, were contained comparably in these three categories of hepatitis B particles. In remarkable contrast, small spherical particles derived from plasma containing antibody to HBeAg were very low in the content of any Pre-S polypeptides. P31 and P39 showed higher activities for poly-HSA receptor than their glycosylated versions. When Dane particles were digested with trypsin, the poly-HSA receptor was deprived in parallel with the loss of antigenicity for Pre-S(2) sequence. The antigenicity for Pre-S(1) sequence was much less affected, and that for the product of gene S was virtually unchanged by the digestion.
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PMID:Polypeptides coded for by the region pre-S and gene S of hepatitis B virus DNA with the receptor for polymerized human serum albumin: expression on hepatitis B particles produced in the HBeAg or anti-HBe phase of hepatitis B virus infection. 300 21

The pre-S2 portion of hepatitis B virus surface antigen P31 gene was modified to make gene products resistant to trypsin-like proteases in Saccharomyces cerevisiae. The coding sequence for 6 amino acids (Ser44 - Thr49) including Arg48 was removed, and the altered gene was inserted into an expression vector. The modified HBsAg P31 (M-P31c) gene products, consisting of GP37 and GP34, formed particles having both HBsAg antigenicity and polymerized-albumin receptor activity. Since the M-P31c particles can elicite two kinds of protective antibodies against hepatitis B virus, anti-S and anti-pre-S2 antibodies, the M-P31c particles are expected to be potentially effective to S-nonresponders.
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PMID:Synthesis in yeast of hepatitis B virus surface antigen modified P31 particles by gene modification. 302 94

Two preparations of human serum albumin (Cohn fraction V), when subjected to high-performance liquid chromatography, were found to contain albumin polymers with molecular sizes of 35 X 10(4) daltons or greater (breakthrough fraction), as well as tetramers, trimers and dimers. They bound to the envelope polypeptide of hepatitis B virus composed of translation products of the pre-S2 region and the S gene (P31), carrying the receptor for polymerized human serum albumin, with an activity increasing in parallel with the degree polymerization.
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PMID:Interaction between human albumin polymers and the envelope polypeptide of hepatitis B virus (P31) containing the translation product of the pre-S2 region. 366


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