Conjugates of Hepatitis B Surface Antigen (14-32)Pre-S2 Region with N-Acetylmuramic Acid, N-Acetylnormuramic Acid, and Their L-Alanyl-D-Isoglutamine Derivatives: Synthesis and Studies on Immunogenicity

1992 ◽  
Vol 57 (1) ◽  
pp. 204-211
Author(s):  
Zbigniev Maćkiewicz ◽  
Hanna Świderska ◽  
Maria Kalmanowa ◽  
Zygfryd Smiatacz ◽  
Adam Nowosławski ◽  
...  

Four novel analogs of hepatitis B virus surface antigen (14-32)Pre-S2 region fragment attached covalently to N-acetylmuramic acid, N-acetylmuramyl-L-alanyl-D-isoglutamine, N-acetylnormuramic acid, and N-acetylnormuramyl-L-alanyl-D-isoglutamine were synthesized by the solid phase method. The ability of analogs to induce cellular and humoral immunity to native HBsAg was tested on rabbits. Cellular immune response occurred in vitro, and HBs antibodies were detected in all immunized animals. No additional adjuvants were used in the tests.

1988 ◽  
Vol 53 (11) ◽  
pp. 2952-2956 ◽  
Author(s):  
Bernard Lammek ◽  
Zbigniew Maćkiewicz ◽  
Izabela Derdowska ◽  
Hanna Świderska ◽  
Adam Nowosławski ◽  
...  

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.


Pteridines ◽  
2018 ◽  
Vol 29 (1) ◽  
pp. 1-5
Author(s):  
Songül Ü Ünüvar ◽  
Hamza Aslanhan ◽  
Zübeyde Tanrıverdi ◽  
Fuat Karakuş

Abstract Hepatitis B is a life-threatening viral liver infection caused by the hepatitis B virus. Neopterin is regarded as an immunologic biomarker of several diseases related to activation of the cellular immune system. Hepatitis B infection is associated with increased production of cellular immune system markers. We aimed to investigate whether there is a relationship between hepatitis B surface antigen-positivity (HBsAg +) and neopterin to determine the role of neopterin in the early diagnosis of hepatitis B infections. Seventy-two HBsAg (+) patients with normal liver function tests and forty-three controls were included in the study. Neopterin levels were 17.6 ± 0.13 nmol/L in HBsAg (+) patients; and 9.12 ± 0.09 nmol/L in infection-free controls, respectively. Compared to the control group, a statistically significant increase (p < 0.001) in the serum neopterin levels of the patients was observed. No significant relationship was determined between neopterin levels and age/sex (both, p > 0.05). With overstimulation of interferon-gamma, the production of neopterin increases by monocytes/macrophages. Likewise with other diseases associated with an activated cellular immune system, this study shows that neopterin can be a predictive biomarker for persistent carriers of hepatitis B infection.


Microbiology ◽  
2000 ◽  
Vol 81 (5) ◽  
pp. 1165-1174 ◽  
Author(s):  
Klaus M. Weinberger ◽  
Tanja Bauer ◽  
Stephan Böhm ◽  
Wolfgang Jilg

Chronic carriers of hepatitis B virus (HBV) usually show hepatitis B surface antigen (HBsAg) in their sera, which is considered the best marker for acute and chronic HBV infection. In some individuals, however, this antigen cannot be detected by routine serological assays despite the presence of virus in liver and peripheral blood. One reason for this lack of HBsAg might be mutations in the part of the molecule recognized by specific antibodies. To test this hypothesis, the HBV S gene sequences were determined of isolates from 33 virus carriers who were negative for HBsAg but showed antibodies against the virus core (anti-HBc) as the only serological marker of hepatitis B. Isolates from 36 HBsAg-positive patients served as controls. In both groups, a considerable number of novel mutations were found. In isolates from individuals with anti-HBc reactivity only, the variability of the major hydrophilic loop of HBsAg, the main target for neutralizing and diagnostic antibodies, was raised significantly when compared with the residual protein (22·6 vs 9·4 mutations per 1000 amino acids; P<0·001) and with the corresponding region in the controls (22·6 vs 7·5 exchanges per 1000 residues; P<0·001). A similar hypervariable spot was identified in the reverse transcriptase domain of the viral polymerase, encoded by the same nucleotide sequence in an overlapping reading frame. These findings suggest that at least some of the chronic low-level carriers of HBV, where surface antigen is not detected, could be infected by diagnostic escape mutants and/or by variants with impaired replication.


1994 ◽  
Vol 28 (9) ◽  
pp. 1014-1017
Author(s):  
Christine A. Lindsay ◽  
Ken Dang ◽  
James M. Adams ◽  
Ching Nan Ou ◽  
Carol J. Baker

OBJECTIVE: To determine in vitro the compatibility of reconstituted intravenous immunoglobulin (IVIG) (Gammagard, Baxter-Hyland) with five different neonatal and pediatric intravenous solutions in Viaflex polyvinyl chloride bags. DESIGN: In vitro compatibility study. INTERVENTIONS: Samples were taken at time=0, 10, 30, 60, 90, and 120 minutes and at 4, 8, 12, and 24 hours and assayed for total immunoglobulin G content and antibodies to hepatitis B surface antigen. Type III group B Streptococcus (GBS) and opsonic activity for type III GBS were analyzed at time=0, 60, and 120 minutes and 12 and 24 hours. All results were compared with those from pure IVIG. RESULTS: Our results demonstrate that mixing IVIG with intravenous solutions commonly used in the care of premature infants (dextrose 5% in water [D5W], D15W, D5W/NaCl 0.225%, and total parenteral nutrition [TPN]) does not significantly alter total immunoglobulin G concentrations or concentration of antibodies to hepatitis B surface antigen or type III GBS. As well, the in vitro functional activity for type III GBS of the IVIG, when mixed with these solutions for up to 24 hours, remained intact. An apparent decrease in bactericidal killing was seen with the IVIG/central TPN mixture. This apparent decrease was found to be an artifact of the high concentration of glucose (20 percent) in the solution. CONCLUSIONS: We propose that Gammagard may be mixed with these solutions through Y-site connections without loss of antibody content or functional activity of the IVIG.


1979 ◽  
Vol 25 (1) ◽  
pp. 178-182 ◽  
Author(s):  
H Park

Abstract I describe a new technique for improving the sensitivity of the solid-phase "sandwich" assay, by using the through-passage receptacle in a novel flow-communication device. The technique allows a large volume of serum to flow through the antibody-coated receptacle repeatedly during the incubation and is thus termed the "flow-through large-volume incubation" method. Binding of 125I-labeled hepatitis B surface antigen to its corresponding antibody on a solid-phase by this method was more rapid and persistent than binding by the conventional method. When the method was applied to the first incubation of the sandwich assay, the test for the antigen was rendered four-, eight-, and 32-fold as sensitive as an accepted third-generation test for the antigen, by incubating 5-mL volumes of serum at (a) room temperature for 18 h, (b) 45 degrees C for 8 h, or (c) room temperature for seven days, respectively.


1986 ◽  
Vol 111 (1) ◽  
pp. 125-131 ◽  
Author(s):  
P. Melin ◽  
J. Trojnar ◽  
B. Johansson ◽  
H. Vilhardt ◽  
M. Åkerlund

ABSTRACT With the aim of developing inhibitors of vasopressin-and oxytocin-induced uterine activity, 17 analogues of 1-deamino-oxytocin were synthesized by the solid-phase method. Modifications were made at positions 2, O-methyltyrosine (Tyr(OMe)) and O-ethyltyrosine (Tyr(OEt)),d-Tyr,d-Tyr(OEt),d-Trp; 4, Val,Thr and 8, Orn,Cit,Arg,d-Arg. The analogues were tested for antiuterotonic activity in vitro and in vivo in the rat and in vitro on myometrial strips from non-pregnant women and pregnant women at term. Their selectivity was also investigated in blood pressure and antidiuretic bioassays in rats. Results were compared with those from an original antiuterotonic analogue 1-deamino-2-Tyr(OEt)-oxytocin (d(OEt)-oxytocin). In the rat in vitro and in vivo all analogues possessed higher antiuterotonic activity than d(OEt)-oxytocin. The negative logarithm of the molar concentration of the antagonist which reduced the effect of a dose of agonist to that of half the dose (pA2) was between 7·6 and 8·9 for all the new inhibitors compared with 7·2 for d(OEt)-oxytocin. The highest pA2 value was found for 1-deamino-2-Tyr(OMe)-8-Orn-oxytocin (8·9 ± 0·2, s.e.m.) and 1-deamino-2-Tyr(OEt)-4-Thr-8-Orn-oxytocin (8·9 ± 0·6). In myometrium from non-pregnant women the most potent peptide was 1-deamino-2-d-Tyr(OEt)-4-Th r-8-Orn-oxytocin (17·2 ± 2·0 times more potent that d(OEt)-oxytocin). In myometrium from pregnant women the inhibitory effects of the majority of the analogues were less pronounced. In the rat in vivo the most potent analogue 1-deamino-2-d-Trp-4-Val-8-Orn-oxytocin was 19·9 ± 2·5 times more active than d(OEt)-oxytocin. Exchanging l-tyrosine for the d form generally increased inhibitory activity as well as specificity of the analogues. Alkylation of the d-tyrosine residue did not appear to be necessary for inhibition. Substitution with d-tryptophan at position 2 gave analogues with high inhibitory potency in the rat in vitro and in vivo, but which exhibited weak effects in women in vitro. There was no correlation between the inhibitory effects on myometrium from non-pregnant and pregnant women nor between rat and human data. The high antiuterotonic activity of 1-deamino-2-d-Tyr(OEt)-4-Val-8-Orn-oxytocin and 1-deamino-2-d-Tyr(OEt)-4-Thr-8-Orn-oxytocin combined with low blood pressure and antidiuretic effects make these two analogues interesting for clinical studies. J. Endocr. (1986) 111, 125–131


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