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W Jilg

Publications and source records attributed to W Jilg.

At least 19 recordsLinked to original sources

[Hepatitis B vaccination of children and adolescents].

In the 14 years that have passed since its introduction, the hepatitis B vaccine has proved to be highly immunogenic, effective and very well tolerated. The vaccination, previously performed only in persons at high risk of contracting hepatitis B, in particular medical personnel, has appreciably reduced the incidence of hepatitis B in this group. The incidence of the disease in the general population, however, has been reduced only marginally. Thus, the sole possibility of resolving the hepatitis B problem is to introduce general vaccination. To this end, the The Ständige Impfkommission (STIKO) has included hepatitis B vaccination in the catalog of vaccinations for children and adolescents. The greatest importance must probably attach to vaccination of young children, in whom hepatitis B vaccination is carried out along the same lines as the diphtheria, pertussis and tetanus vaccination, within the framework of which it can therefore be administered, thus making possible a wide application. However, the 12-15 year-old age group should also be involved in the vaccination program, for this is the group on the threshold of the periods of greatest danger of infection, which begins with the initiation of first sexual relationships.

Adolescent

Booster immunization of low- and non-responders after a standard three dose hepatitis B vaccine schedule--results of a post-marketing surveillance.

Seventy-nine low-responders and 83 non-responders after a previous three-dose hepatitis B (HB) vaccine course at 0.1, and 6 months were enrolled to receive additional 20 micrograms recombinant HB vaccine doses every 2 months until all had anti-HBs levels > or = 100 mIU ml-1. After the first booster, 65.4% had anti-HBs levels > or = 100 mIU ml-1, 17.9% were low-responders (10-99 mIU ml-1), and 16.7% remained non-responders (< 10 mIU ml-1). All complying non-responders developed anti-HBs levels > or = 100 mIU ml-1 after the third booster at the latest, whereas all low-responders reached this level after the second booster. Although body mass index affected the response to the first hepatitis B booster, when full compliance to regular revaccination was ensured, all non- and low-responders eventually reached sufficient anti-HBs levels.

Adolescent

Long-term persistence of anti-HAV antibodies following active immunization with hepatitis A vaccine.

Seventy-one anti-hepatitis A virus (HAV) negative volunteers were immunized against hepatitis A. An inactivated hepatitis A vaccine (HAVRIX, SmithKline Beecham), derived from tissue cell cultures, at single doses of 720 ELISA units was used following a schedule of vaccinations at month 0.1 and 6. The vaccines were tested for the presence of HAV antibodies 1 month after each vaccination and then after 2, 3, 4 and 5 years. The annual decrease of anti-HAV titres was 25%. Five years after vaccination a protective antibody titre, varying between 20 and 5200 mIU ml-1, could be demonstrated in all 47 retested volunteers with a geometric mean titre (GMT) of 442 mIU ml-1. Levels of anti-HAV-antibodies following active immunization were significantly higher in female volunteers. This could be consistently demonstrated throughout the observation period. Based on these data the antibody persistence was calculated over time. GMTs at protective levels higher than 20 mIU ml-1 can be expected to persist for at least 15 years.

Adult

Immunogenicity of a recombinant hepatitis B vaccine in adults.

OBJECTIVES: To evaluate the immunogenicity and reactogenicity of a recombinant hepatitis B vaccine in health care staff under routine use and unselected conditions and to investigate factors that influence the response to vaccination. METHODS: This prospective postmarketing surveillance study was performed in unselected health care staff and their relatives (age range, 12-60 years) at 58 hospitals. Overall, 880 subjects were administered a 20-microgram dose of a vaccine at 0, 1, and 6 months according to the prescribing information and under routine hospital practice, and they were tested for antibody to hepatitis B surface antigen after the third dose at the hospitals routine laboratory. The principal outcome measures were antibody to hepatitis B surface antigen titers that were expressed as the seroprotection rate (SPR) (SPR [given as a percentage], > or = 10 mlU/ mL), spontaneously reported adverse events, and geometric mean titers (in milli-international units per milliliter). RESULTS: The compliance to the 3-dose schedule under routine hospital practice was 98.1%. The immune response was good in all age groups, and the overall SPR was 97.8% at 1 month after the third dose in field conditions with unselected health care workers. The SPR in vaccinees (age range, 40-59 years) was close to 95%. Age (P < .001), smoking (> or = 10 cigarettes per day) (P < .001), Broca index (> 110%) (P < .001), antibody to hepatitis B surface antigen testing (> 8 weeks after the last dose) (P = .03), chronic underlying disease (P = .04), and male gender (P = .04) were factors associated with lower geometric mean titers in routine vaccine use. No serious adverse events were reported. CONCLUSION: The large immune response that was elicited by this hepatitis B vaccine in adults under daily routine field conditions reflected reality, with a high SPR also found in elderly and other persons with risk factors associated with a lower immune response.

Adolescent

[Hepatitis C].

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Adult

Significance of imported hepatitis B virus infections.

The risk of imported hepatitis B in Germany and comparable European countries seems to be low as long a suitable control measures are taken. These measures include testing for hepatitis B markers of immigrants from highly endemic areas as well as of individuals who stayed for a longer period of time in such regions, information of chronic carriers of hepatitis B virus and vaccination of their contacts, and vaccination of travellers to endemic regions who run an increased risk for contracting hepatitis B as e.g. i.v drug users or sex tourists.

Carrier State

Individuals with antibodies against hepatitis B core antigen as the only serological marker for hepatitis B infection: high percentage of carriers of hepatitis B and C virus.

BACKGROUND/AIMS: Several reports have unequivocally demonstrated that some individuals with antibodies against hepatitis B core antigen as the only serological marker for hepatitis B infection are chronic carriers of the hepatitis B virus. Nevertheless, conflicting data exist about the frequency of this phenomenon; its cause is unknown. METHODS: In a prospective study we tested individuals who were positive for anti-HBc alone for HBV-DNA as well as for coexisting infections with human immunodeficiency virus and hepatitis C virus. RESULTS: Using polymerase chain reaction with primer pairs from three different regions of the hepatitis B virus genome, we found 54 of 164 individuals (32.9%) with anti-HBc alone to be positive for hepatitis B virus, the majority of them showing very low hepatitis B virus concentrations. 14.3% were human immunodeficiency virus positive; half of them were also hepatitis B virus carriers. Surprisingly, 62 of 153 participants (40.5%) in this study showed antibodies against hepatitis C virus, and about two thirds of the latter were also positive for HCV-RNA. This finding could be confirmed by a retrospective analysis of all people tested for hepatitis B virus markers and anti-HCV in our institution during the 2 years before the prospective study was begun. Again, a high correlation was found between the presence of anti-HCV and anti-HBc alone: 49.2% of individuals with anti-HBc only were anti-HCV positive also, compared to 26.8% of HBsAg carriers and only 10% of individuals showing the serological pattern of past hepatitis B. CONCLUSIONS: Thus our study of individuals positive for anti-HBc alone revealed a high number of carriers of hepatitis B virus and hepatitis C virus among them; furthermore, we found some evidence that hepatitis C virus infection may favour this unusual hepatitis B virus marker pattern.

Adult

Selective risk group strategies in Europe.

Most countries in northern and western Europe belong to areas with a low endemicity of hepatitis B virus (HBV). When HBV vaccines became available, these countries adopted a vaccination strategy that targeted groups at high risk of hepatitis B. However, it became obvious that this strategy, despite giving good protection to those who had been vaccinated, had largely failed. This was firstly because, with few exceptions (e.g. haemodialysis patients and haemophiliacs), only medical and dental workers were vaccinated in any great numbers, whereas only a few individuals in other risk groups were reached. Second, it was found that less than half of all hepatitis B cases occurred in individuals in typical high-risk groups. In Germany, for example, about three-quarters of all infections occur in people who would never be reached by the high-risk vaccination strategy, most of these individuals having been infected by heterosexual contact. Thus a universal vaccination strategy has to be implemented to control the spread of hepatitis B in the population and to eventually eliminate the disease.

Europe

Specific cytotoxic T lymphocytes recognize the immediate-early transactivator Zta of Epstein-Barr virus.

We identified the immediate-early transactivator Zta of Epstein-Barr virus as a target for specific cytotoxic T lymphocytes (CTL). Cells pulsed with overlapping synthetic peptides representing the entire amino acid sequence of Zta proved to be efficient for the in vitro stimulation of Zta-specific CTL in several donors. With peptide-pulsed target cells, we found that CTL from several donors recognize a peptide comprising 15 amino acids. The immune response against this peptide exerted by CTL lines from different donors was found to be restricted by two different molecules of the major histocompatibility complex: HLA-B8 and HLA-Cw6. The latter molecule could for the first time be identified as a restricting element for a CTL response. The epitope of the HLA-B8-restricted CTL could be mapped to an octameric sequence between amino acid positions 190 and 197 of the Zta protein, whereas the minimal epitope of HLA-Cw6-restricted CTL consists of 11 to 15 residues between positions 187 and 201. Thus, the HLA-B8 and HLA-Cw6 epitopes widely overlap but are not completely identical. In vitro stimulation of blood lymphocytes from a panel of HLA-B8-positive or HLA-Cw6-positive virus carriers, using autologous cells pulsed with the Zta peptides comprising the HLA-B8 or HLA-Cw6 epitope, respectively, revealed in both cases that most of these donors developed a Zta-specific cytotoxic activity. These data, as well as the high spread of the major histocompatibility complex molecules HLA-B8 and HLA-Cw6 in most populations, suggest that an efficient CTL response directed against gene products of the immediate-early group of the lytic cycle exists in vivo in a considerable portion of virus carriers. A CTL response against proteins expressed immediately after the switch into the lytic cycle could eliminate lytically activated cells at an early stage and would thus efficiently prevent the production and release of progeny virions.

Amino Acid Sequence

The Epstein-Barr virus-encoded glycoprotein gp 110 (BALF 4) can serve as a target for antibody-dependent cell-mediated cytotoxicity (ADCC).

Antibody-dependent cell-mediated cytotoxicity (ADCC) is thought to play a major role in controlling the spread of the Epstein-Barr virus (EBV) in an infected individual. Recently, the viral membrane protein gp 350/220, which is also expressed at the surface of the virus producing cell, was identified as a target for ADCC reactions. Due to its glycoprotein nature, the EBV protein gp 110 is another possible ADCC target. It is one of the most abundant proteins found during the late phase of viral replication; until now, however, researchers have not been able to localize it on the surface of EBV positive cells. By means of recombinant vaccinia viruses containing the genes for gp 350/220 and gp 110, respectively, we expressed these proteins in lymphoblastoid cells, which were then used as targets in ADCC studies with sera from EBV-positive and -negative individuals. In these experiments we were able to demonstrate the feasibility of our approach for the investigation of EBV-specific ADCC reactions and could confirm the role of gp 350/220 as an ADCC target. Furthermore, we were able to show that gp 110 can also be recognized in an ADCC reaction, proving that at least some gp 110 molecules must be expressed at the cell surface.

Antibody-Dependent Cell Cytotoxicity

Efficient foreign gene expression in Epstein-Barr virus-transformed human B-cells.

Epstein-Barr virus (EBV) is a herpesvirus that transforms B-cells (B-LCL) and has undergone intense scrutiny owing to its association with Burkitt's lymphoma, nasopharyngeal carcinoma, and immunoblastic lymphomas. B-LCL have also proven useful in the study of human immunology. We describe a novel system for inducing efficient foreign gene expression in B-LCL using biotinylated adenovirus as an endosome-disrupting agent. Plasmid DNA is coupled to the exterior of viral particles by streptavidin-polylysine chimeric proteins. Up to 67% of B-LCL may be induced to express foreign genes in vitro in transient expression systems, and gene expression lasts for at least 17 days. We have expressed firefly luciferase, beta-galactosidase (beta-gal), chloramphenicol acetyltransferase, HIV gag, and env genes, as well as infectious HIV, and the EBV-specific BZLF gene in B-LCL with this system. In vivo delivery of a beta-gal reporter gene to B-LCL was documented in a SCID mouse model. Potential applications include study of genetic regulation of EBV infection and transformation events, study of potential gene therapies for EBV-related B-cell tumors, and production of antigen-presenting cells for use in immunologic assays. Because of the high percentage of cells transformed and the length of foreign gene expression, the possibility of examining foreign gene expression in transient assays, without selection for clonal populations, exists.

Animals

Different activation of Epstein-Barr virus immediate-early and early genes in Burkitt lymphoma cells and lymphoblastoid cell lines.

Specific expression of the Epstein-Barr virus (EBV) immediate-early and early gene products Zta, Rta, I'ta, and MSta by a recombinant vaccinia virus system allowed us to analyze the first steps in the induction of the lytic cycle in EBV-infected Burkitt lymphoma (BL) cells and lymphoblastoid cell lines (LCLs). Significant differences in the induction of early genes were found between these cell types: whereas in BL cells the trans activator Zta was found to induce key steps of the early lytic cycle, only minor activities of Zta were noted in LCLs. Contrary to Zta, the trans activator Rta was found to be highly effective in LCLs. These observations suggest that Rta may play an important role in the activation of the early lytic cycle in LCLs, although it cannot be activated by Zta. The latter may be a reason for the lower tendency of LCLs to switch into the lytic cycle compared with BL cells or differentiated epithelial cells.

B-Lymphocytes

Substantial decline of notified hepatitis B in major parts of Europe after 1985.

A decline in the incidence of notified hepatitis B cases has been observed in major parts of Europe since the mid-1980s. Sweden may be taken as an example of a low prevalence area in the north where notifications of acute hepatitis B declined from 6 cases/100,000 inhabitants in 1985 to only 3/100,000 annually in 1988-91. Choosing W. Germany as an example from central Europe, the notification rate of acute hepatitis B declined from 11 cases/100,000 inhabitants in 1984 to 6-8/100,000 in 1988-91. In Italy, a dramatic decline in hepatitis B infections has occurred since 1985, according to the national hepatitis surveillance system (SEIEVA), from 12 cases/100,000 inhabitants in 1985 to 5/100,000 in 1988-91. A similar trend has also been observed in the USA which seems to be unrelated to vaccination, since only limited vaccination programs have been initiated in high-risk groups. Also in Europe, changed sexual and needle-usage practices in risk groups such as drug addicts and male homosexuals have probably contributed to the observed decline. In southern Europe, rapidly improving socio-economic conditions and improved medical precautions against hepatitis B have probably also been important factors.

Europe