A placebo-controlled dose response study of the reactogenicity and immunogenicity of a live cold-recombinant influenza B virus vaccine in healthy volunteers.

A live cold-recombinant influenza B virus vaccine (RB77) was given intranasally in a placebo-controlled, double blind study to volunteers in dosages of 10(7.9) EID50/ml, 10(7.25) EID50/ml, 10(5.7) EID50/ml. The tolerability, safety, and immunogenicity of the vaccine were investigated. No revertant virus was found in nasal swabs taken after immunisation. Local reactions were mild and showed a significant increase over the placebo only in the highest dose group. Systemic reactions were not different from the placebo. A significant increase in haemagglutinin inhibition titre was found in the highest dose group against the immunising strain (RB77) and the two wild strains B/TEC and B/Sing.

[Incidence of hepatitis B virus infection in the medical personnel of physicians' offices]. / Hepatitis-B-Virus-Durchseuchung des medizinischen Personals in Arztpraxen.

Serological examination to determine anti-HBc antibodies in 1487 medical personnel working with practitioners in Essen revealed a hepatitis B virus incidence rate of 12.8%. The incidence rate depended on age, years of service, and nature of duties. Anti-HBc examination of medical personnel is cost-saving in view of high cost of vaccination. It can be omitted only in beginners if certain conditions are fulfilled (anti-HBc rate below 5%).

T lymphocyte populations in multiple sclerosis.

In 36 patients representing different clinical stages of multiple sclerosis (MS) (9 patients with acute exacerbations; 21 patients in remission; 5 patients with chronic progressive MS) determinations of T lymphocyte populations using monoclonal antibodies against surface antigens (OKT3 (pan T cells), OKT4 (helper T cells), OKT8 (cytotoxic/suppressor T cells] were performed. Compared to the control group (40 healthy individuals) a clear elevation of the T4/T8 ratio was found in acute exacerbations and to a lesser degree in patients with inactive phases of MS. Patients with chronic progressive disease did not show increased T4/T8 ratios. Serial determination of lymphocyte populations after corticosteroid therapy in 10 selected patients revealed no significant changes which could be attributed to this therapeutic modality. Pathogenetic and clinical implications of the shifts in surface antigen expression of T lymphocyte populations mirroring the clinical course of MS are discussed.

[Immunity against influenza virus types A and B in the Ruhr region]. / Immunität gegen die Influenzavirus-Typen A und B im Ruhrgebiet.

Haemagglutination-inhibiting antibodies against influenza virus types A and B were determined in the sera of 733 healthy persons among the population of the Ruhr region. The receptivity rate for the total population to strains A/Philippines 2/82 (H3N2) and A/Brazil 1/78 (H1N1) was 60% and 80%, respectively. It was as high as greater than 95% with respect to type B (Hongkong). These findings support the call for more widespread anti-influenza vaccination during the winter half-year.

Active hepatitis B immunization with an experimental German vaccine. I. Immunogenicity studies in healthy adults. II. The primary 19 S and 7 S responses to HBsAg in healthy adults. III. Immunogenicity studies in hemodialysis patients.

The immunogenicity of an experimental german hepatitis B vaccine has been evaluated in 343 healthy adults. Three doses of vaccine induced anti-HBs antibodies in 94 to 100% of the vaccines. Different batches and doses of vaccine did not significantly influence the seroconversion rates at the end of the vaccine trial. Higher doses were followed by more rapidly and more vigorously occurring anti-HBs-levels. Significant differences were noticed between the 40 micrograms- und the 10- or 8 micrograms-doses. Variation of schedules (0-1-6 or 0-1-5) did not result in significant differences. Batch-no. I/B 070881 induced significant lower anti-HBs levels than batch-no. II/310781. Females developed significant higher anti-HBs values than males, younger vaccinees higher than older vaccinees. Rate zonal ultracentrifugation analysis of anti-HBs-positive sera collected after vaccination regularly revealed anti-HBs of the IgM class in case of early and high immune response to the vaccine. Individuals characterized by a late onset of anti-HBs production developed anti-HBs antibodies of the IgG class only. The vaccine induced an anti-HBs response in 64 to 75% of hemodialysis patients. The conversion rates and the achieved anti-HBs levels were significantly higher in young and/or female patients than in old and/or male patients.

Active hepatitis B immunization with an experimental German vaccine. IV. Reactogenicity studies in healthy adults and in hemodialysis patients.

Reactogenicity testing was performed accompanying vaccination with the experimental German Hepatitis B Vaccine. 509 individuals, among them 343 healthy adults and 166 hemodialysis patients, were vaccinated with three doses of vaccine. The evaluation of questionnaires indicated that local and systemic adverse reactions were of low intensity and short duration. The rates of reactions were highest following the first and lowest after the third vaccination. The vaccine did not induce immunopathological alterations. The vaccine was non-infectious and thus not the cause of hepatitis B infections nor of other viral or bacterial infections.

[Demonstration and occurrence of IgM-type hepatitis A viral antibodies]. / Nachweis und Vorkommen von Hepatitis-A-Virus-Antikörpern des IgM-Typs.

Hepatitis-A antibody of the IgM class can be demonstrated in serum by radio-immunoassay quickly, relatively cheaply and simply. The diagnosis of fresh or recent hepatitis-A virus infection can be made from a single serum sample in a single test. Epidemiological analysis of the positive findings obtained in 1981 gave the following results: 1. Hepatitis-A is, in Germany, largely a disease of young adults, with an average age of 24 years. But cases still occurred above the age of 50.2. Among foreigners positive results were obtained already in children (average age 7 years). 3. While in foreigners the disease predominantly occurred in the last four months of the year, among Germans the distribution had three peaks related causally to the holiday months of April, July and October.

[Regulatory T-lymphocytes in the immune deficiency syndrome]. / Regulatorische T-Lymphozyten bei Antikörpermangelsyndrom.

A 25-year-old patient presented with hypogammaglobulinemia diagnosed at the age of 7, causing recurrent infections of the gastrointestinal and bronchial tracts. He was treated with gammaglobulins and infusions of fresh human plasma. At admission he had an exacerbation of his chronic enteric symptoms. X-ray investigation and coloscopy showed mucosal changes as in enteritis regionalis . A biopsy of rectal mucosa showed accumulations of amyloid. Routine examination of humoral and cellular immune parameters revealed a pattern characteristic for common variable immunodeficiencies. Analysis of T-cell subsets with monoclonal antibodies of the OKT series showed unusually high relative numbers of OKT8+ cells (suppressor-T-lymphocytes) and a comparatively low number of OKT4+ cells (helper-T-lymphocytes). Suppressor-T-cells exert inhibitory effects on B-lymphocyte function (i.e. antibody production). The numerical excess of T-lymphocytes with suppressive properties could be a pathogenetically important factor with immunotherapeutic implications in a number of non-classifiable immunodeficiency syndromes.

[A radioimmunoassay for the determination of human myoglobin: lower detection limit, precision and use in control of myoglobinuric kidney failure]. / Radioimmuntest zur Bestimmung von Humanmyoglobin: Untere Nachweisgrenze, Präzision, Verlaufskontrolle beim myoglobinurischen Nierenversagen.

The lower detection limit of a radioimmunoassay for human myoglobin was determined by two "precision from day to day" methods (90% and 3 s methods), and by two "precision in series" methods (95% confidence range and the method of Markowetz & Munz). According to Markowetz & Munz, the lower detection limit (as a measure of sensitivity) is the lowest myoglobin concentration which, in 15-fold assays, shows no binding value in common with that of the next highest concentration, and no activity value in common with that of the reference binding value. On theoretical grounds (precision in series) and from a practical standpoint (determination of the lower detection limit using one sample assay), this method is the most suitable for the determination of the lower detection limit as a measure of sensitivity. It remains to be seen whether this is a valid generalization for other methods.

[Age- and sex-dependent changes in human T-lymphocyte subpopulations]. / Alters- und geschlechtsabhängige Veränderungen humaner T-Lymphozyten-Subpopulationen.

Changes in the expression of T-lymphocyte membrane antigens are seen in many diseases, particularly in autoimmune diseases. The reliability of these parameters, as well as their changes associated with age and sex, were examined in 232 healthy subjects using monoclonal antibodies of the OKT series. The precision of the indirect immunofluorescence method for determining the T3, T4 and T8 antigens (corresponding antibodies OKT 3, OKT 4, OKT 8) is within a range expected for biological testing methods (median variation coefficients 7-20%). In both sexes a statistically significant reduction of the T3+ cells (P = 0.0001; T-lymphocytes) and of the T8+ cells (P = 0.0004; T-suppressor lymphocytes) was seen with increasing age. In women (n = 115) the rate of T3+ and T4+ cells was 2-5% higher on the average (the T4+ cell population contains T-helper lymphocytes). According to these findings there is a statistically significant increase of the T4+ to T8+ cell ratio (P = 0.0001); due to the greater number of helper cells, the average T4/T8 quotients are greater in women than in men (P = 0.0076). The changes in the ratio of T-helper to T-suppressor cells are discussed as predisposing factors in the genesis of autoimmune diseases.

Uptake and elimination of hepatitis B immunoglobulins after intramuscular application in man.

Hepatitis B immunoglobulins of 4 different manufacturers were administered intramuscularly into 37 healthy adults. Each person received an amount of 0.1 ml per kg bodyweight. Blood samples were taken on days 3, 7, 14, 21, 28, 63, 98 and 126 after passive immunization. The anti-HBs serum levels were determined using the International Reference Preparation of anti-HBs as standard reagent. The highest serum levels were seen on day 3 (38.9% of the test persons), day 7 (41.7%), day 14 (11.1%), and day 21 (8.3%) after application of the immunoglobulins with mean values between 138 and 355 mU anti-HBs/ml. The half-life of the preparations in man showed mean values between 17.5 and 25 days. The shortest half-life was 5.9 and the longest 35 days. Four months after passive immunization the anti-HBs levels had decreased to a percentage of 1.2 to 2.5 of the maximum serum concentration (1.7 to 8.9 mU anti-HBs/ml). The passive immunization via the intramuscular route does not accomplish an instantaneously available, maximum anti-HBs titer. There seems to be a great range of variation in uptake and elimination of the immunoglobulins in man. Still, since preparations for intravenous application are not at hand, hepatitis B immunoglobulins for intramuscular use must play a major role in post-exposure prophylaxis of hepatitis B virus infection.