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Biomedical subjects

W Jilg

Publications and source records attributed to W Jilg.

At least 109 records · Page 6Linked to original sources

What's new in hepatitis delta virus?

Seven years of clinical and laboratory research have provided us with a rather good knowledge of the infectious agent that causes hepatitis delta. This agent is a small RNA containing virus (hepatitis delta virus), which is functionally incomplete and needs the help of hepatitis B virus for infection and replication. It is unique also in respect to its RNA, which is smaller than the RNA of every other known RNA virus, but larger than the RNA of the viroids of higher plants. Animal experiments as well as clinical studies showed that hepatitis delta virus infection can be transmitted either simultaneously with hepatitis B, leading to a clinical picture which usually resembles that of hepatitis B alone, or as superinfection of a chronic HBsAg-carrier. The latter often leads to severe, and sometimes fatal, acute hepatitis, followed by chronic liver disease in as many as 30-40% of cases. The hepatitis delta virus is distributed world-wide, showing a high endemicity in Italy and some Arab countries, but also in certain risk groups such as intravenous drug addicts and haemophilics. Further epidemiological studies will probably reveal other foci where the hepatitis delta virus is endemic; especially in Africa, areas of high endemicity of hepatitis delta virus are suspected. Extensive research on delta agent is continuing: further clinical studies, using the highly sensitive method of DNA-RNA-hybridization for the detection of hepatitis delta virus RNA, will tell us more about the role of this virus in acute and chronic hepatitis, and future biochemical and biological research may be expected to increase our insight into the still enigmatic cooperation of the hepatitis delta virus and hepatitis B viruses.

Animals↗

[Viral hepatitis and immunoprophylaxis].

Today we distinguish 4 forms of viral hepatitis: hepatitis A, hepatitis B, hepatitis non-A, non-B and hepatitis occurring in the course of other viral diseases. The viruses of hepatitis A and hepatitis B have been identified but the agent(s) of hepatitis non-A, non-B remain unknown. Inoculation of normal pooled human immunoglobulin provides passive immunity for 2-3 months against hepatitis A but not against hepatitis B or hepatitis non-A, non-B. For passive protection against hepatitis B a special immunoglobulin with a high anti-HBs titer must be used whereas the protection against hepatitis non-A, non-B with immunoglobulin is uncertain. Live attenuated and noninfectious polypeptide vaccines for active immunisation against hepatitis A are currently developed and first clinical trials have begun with the live attenuated vaccine. A vaccine consisting of noninfectious highly purified HBsAg derived from the plasma of HBV carriers is in general use since two years and has proved safe and highly effective and vaccines are now developed from HBsAg obtained through molecular cloning of the HBsAg genome in plasmids and expression of the genome with HBsAg production in yeast cells. First clinical studies with this vaccine are encouraging and these as well as purely synthetic vaccines will in time replace the currently used vaccines. No vaccines could be developed so far against hepatitis non-A, non-B because the agent(s) of this disease are unknown.

Hepatitis A↗

Vaccination against hepatitis B in patients with renal insufficiency.

To define the degree of renal insufficiency at which the immune response to vaccination against hepatitis B is impaired, anti-HB concentrations after vaccination with 20 micrograms HB-Vax at 0, 1 and 6 months were examined in 76 dialysis patients, 24 patients with incipient renal failure (S-creatinine 1.4-3.5mg/dl) and in 43 controls. Compared with controls, seroconversion rate and anti-HB concentrations were significantly (p less than 0.02) lower in patients with incipient renal failure. The time course of anti-HBs in dialysis patients with successful vaccination, either with three doses (0, 1, 6 months) or with five doses (0, 1, 2, 4, 6 months) of HB-Vax was compared with healthy controls. The proportion of patients losing anti-HBs and the decrease of antibody concentration was significantly greater in dialysis patients immunised with three doses of the vaccine. In dialysis patients vaccinated with five doses, the percentage losing HB antibodies was slightly higher than in controls, but final titres after 24 months were comparable.

Adult↗

Clinical evaluation of a recombinant hepatitis B vaccine.

Recombinant hepatitis B vaccine prepared from antigen expressed in yeast was given to 30 healthy young volunteers. Seroconversion rates and anti-HBs levels were compared with those in a control group matched for age and sex who had received plasma-derived hepatitis B vaccine. 4 weeks after the third immunisation results were similar in the two groups. In the recombinant vaccine group the immune response developed more slowly during the early phase and seroconversion rates and mean anti-HBs levels were slightly lower in males; this probably reflects use of a lower dose of recombinant vaccine (10 micrograms compared with 20 micrograms of the plasma vaccine). Side-effects were slight and antibody titres against Candida albicans were not increased in recipients of the recombinant vaccine.

Adult↗

[Hepatitis B and the delta agent].

The delta agent seems to be a defective RNA virus which is dependent on a helper function provided by hepatitis B-virus. Delta agent infection occurs by parenteral transmission either together with hepatitis B-virus, or superimposed on chronic HBV infection. In the first case biphasic hepatitis may result, whereas in the second case mostly an acute delta agent infection develops, which is often followed by chronic delta hepatitis. The delta agent is endemic to certain areas, and also in certain risk groups such as drug addicts, hemophiliacs and polytransfused patients. A delta agent infection should be suspected in case of acute hepatitis in a hitherto clinical inapparent chronic carrier, especially if he belongs to one of the above mentioned risk groups. There is no specific therapy for delta infection, the only prophylactic measure is vaccination against hepatitis B.

Carrier State↗

Hepatitis B surface antigen (HBsAg) subtype-specific antibodies in persons vaccinated against hepatitis B.

One hundred sixty-three persons immunised against hepatitis B with a vaccine containing HBsAg either of adw or ayw subtype were examined for antibodies against the a, d, and y determinants of HBsAg. Sera were tested for antibodies against HBsAg adw and HBsAg ayw separately by a solid-phase radioimmunoassay using polystyrene beads coated with HBsAg of either adw or ayw subtype, and the relative amounts of antibodies against the single determinants were calculated. After the third immunisation, all vaccinees had antibodies against the common determinant a. A quantitative evaluation showed that on average about 50% of HBsAg-specific antibodies were directed against the a determinant, and about 50% against d or y, respectively. However, as only anti-a is protective against cross-infection with other HBsAg subtypes, the degree of immunity of a person vaccinated against hepatitis B should be evaluated by the determination of antibodies to a rather than antibodies against total HBsAg.

Adolescent↗

Evaluation of a reduced dose of hepatitis B vaccine administered intradermally.

Intradermal inoculation of hepatitis B vaccine (HBsAg subtype adw) caused no side effects, but the vaccine was less immunogenic than following intramuscular administration. Intradermal inoculation does not, therefore, offer a major advantage to the generally used intramuscular immunization. A single multisite intradermal administration of a reduced dose of vaccine did not result in a more rapid seroconversion compared to intramuscular inoculation. Although the antibody levels were similar after two intradermal or intradermal or intramuscular injections given 1 month apart, the booster (third injection) at 6 months resulted in anti-HBs levels that were about 10 times higher following intramuscular inoculation as compared to intradermal. All persons immunized developed anti-HBs. The levels of anti-HBs (a and w) were about 30-40% of the total anti-HBs, and the proportion did not change significantly during the course of immunization. Cross-protection against all HBV strains is thus also assured after intradermal administration of vaccine containing only one HBsAg subtype (adw). A skin reaction was elicited only in a small proportion of anti-HBs-positive individuals, and the reaction correlated roughly with the immune responses.

Adult↗

Passive/active immunization against hepatitis B.

No differences in eventual immune-response rates were found between 325 subjects immunized passively/actively against hepatitis B and a control group of 108 subjects vaccinated only actively. The geometric mean titers of antibodies to hepatitis B surface antigen were nearly identical in controls and in a group of 87 individuals immunized passively/actively with the same vaccine lot. Lower geometric mean titers of antibodies to hepatitis B surface antigen were seen in 238 individuals who were vaccinated passively/actively with a different vaccine lot, a difference that may be explained by a somewhat lower immunogenicity in this particular lot. The mean half-life of hepatitis B immunoglobulin was calculated as 24.8 days, and in approximately 90% of vaccines 300,000 mIU of hepatitis B immunoglobulin provided protection until an active immune response had developed.

Adult↗

Strategies for the economic preparation of Epstein-Barr virus proteins of diagnostic and protective value by genetic engineering: a new approach based on segments of virus-encoded gene products.

Immunoprecipitation of Epstein-Barr viral proteins with various sera from normal adults, patients with fresh infectious mononucleosis or nasopharyngeal carcinoma was used to identify antigens which are of importance in the determination of immune status and characteristic of a particular disease. Some genes coding for of these antigens have been localized on the Epstein-Barr virus (EBV) genome by hybrid-selected translation. With the use of sequence data, these genes could then be subcloned from EBV DNA and expressed in eukaryotic and prokaryotic cells. Data on the expression are presented and the application of the methods described for the production of diagnostic reagents and vaccines is discussed.

Antibodies, Viral↗

[Vaccination of uremic patients against hepatitis B].

Hepatitis B vaccine (Merck, Sharp & Dohm) was administered according to various vaccination schedules to 12 patients in preterminal renal failure without haemodialysis treatment, 81 patients on a chronic haemodialysis programme and 43 staff of a nephrological centre. After three-times vaccination (at 0, 1, 6 months) with 20 micrograms HBs antigen, seroconversion occurred in 91% of persons without kidney disease. A double dose (40 micrograms) was given, at the same time intervals, to 29 dialysis patients, with a seroconversion rate of 55% and titre levels less than in those without renal disease. Of 26 dialysis patients given the same dose (40 micrograms) five times (at 0, 1, 2, 4, 6 months), 63% achieved seroconversion with a definitely higher anti-HBs titre than those dialysis patients vaccinated only three times. Passive-active vaccination with 40 micrograms HBs antigen (at 0, 1, 2, 4, 6 months) as well as 3 ml hepatitis B immunoglobulin (at 0, 2 months) was given to 26 dialysis patients. There was a comparable frequency of seroconversion (58%) and a comparable titre rise to those obtained with active vaccination alone. Twelve pre-uraemic patients not requiring dialysis (serum creatinine 753 +/- 184 mumol/l) also were actively vaccinated three times, the results not differing from those in dialysis patients. The findings indicate that patients with renal disease potentially needing dialysis should, in the early stages of renal failure (serum creatinine less than 500 mumol/l) be vaccinated with hepatitis B vaccine.

Antibody Formation↗