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.

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.

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.

[Uptake and elimination of hepatitis B immunoglobulin after intramuscular administration]. / Aufnahme und Elimination von Hepatitis-B-Immunoglobulin nach intramuskulärer Applikation.

After intramuscular administration of four different hepatitis B immunoglobulins at a dose of 0.1 ml/kg body weight, serum anti-HBs antibody titres were followed over four months in 37 healthy persons. Highest serum concentration averaged 138-355 mU anti-HBs/ml and was generally observed on the third or seventh day after passive immunisation. Immunoglobulins were eliminated with a half-life of 17.5-25 days. Four months after injections their concentration was still 1.2-2.5% of the maximally reached serum level. Intramuscular administration of hepatitis B immunoglobulin does not at once achieve effective optimal viral antibody levels in blood. But since there are no special preparations for intravenous use and active immunization is unlikely to be able to provide immediate protection against hepatitis B virus, intramuscular injection remains further on the method of choice in the prevention of hepatitis B after exposure.

Comparison of the morphological alteration and disintegration test (MADT) and the chimpanzee infectivity test for determination of hepatitis B virucidal activity of chemical disinfectants.

The morphological alteration and disintegration test (MADT) as a key indicator for Hepatitis B Virus (HBV) inactivation was compared with the chimpanzee infectivity test using three suspensions of HBV differing in the degree of inactivation as judged by electronmicroscopic studies. The results of the MADT and the chimpanzee studies correlated well. Thus, the MADT, evidently, can replace the laborious, costly and time-consuming animal studies for the evaluation of chemical disinfectants for hepatovirucidal activity.

[Alterations of humoral and cellular immunity after splenectomy (author's transl)]. / Veränderungen des humoralen und zellulären immunsystems nach Splenektomie.

In twenty-seven splenectomized patients, who had undergone splenectomy for trauma (n=13) and thirty-one immunologically healthy persons, matched for age and sex, the following immunological parameters were examined: Serum immunoglobulins M, A, G, D and E, complement factors C3, C4 and the serum haemolytic complement activity (Ch 50), as well as the ratio and in vitro reagibility of B-and T-lymphocytes measured by transformation responses to the non-specific mitogens Phytohämagglutinin, Concanavalin A and Pokeweed-Mitogen. The phagocytic capacity of polymorphonuclear neutrophils was tested by the Nitroblue tetrazolium test. Total peripheral lymphocytes, B- und T-lymphocytes from splenectomized patients were significantly higher than in healthy controls (p less than 0.01). The PHA response in splenectomized patients was significantly depressed (p less than 0.01) as compared to nonsplenectomized controls. Also IgM serum concentration was found to be significantly lower in these patients (p less than 0.01). No differences were observed between patients, who had been splenectomized 7 months to 5 years or 6 to 14 years ago. The comparison of persons splenectomized for traumatological or haematological disorders showed statistically no significant differences. The importance of the spleen for the primary immune response is discussed.

Normal distribution of factor B (Bf) allotypes in multiple sclerosis.

Bf allotypes were determined in 200 multiple sclerosis (MS) patients and compared to analogous control frequencies. No significant deviation of any Bf phenotype was found. Also in HLA-B7- as well as Dw2-positive patients normal Bf frequencies existed.

HLA-antigens and the prognosis of multiple sclerosis.

The histocompatibility pattern of 160 patients with multiple sclerosis (MS) living in the epidemiological area of Southern Lower Saxony was determined and compared to a control population. The only significant difference was the more frequent occurrence of DW2 in the patient group (44% vs. 21%). Taking a progression index (grade of disability divided by the duration of the disease) as a measure for prognosis no difference could be found between the DW2 positive and the DW2 negative patients. The reason why we could not confirm the worse prognosis for DW2 positive patients found by Jersild et al. (1973) and Raun et al. (1980) remains to be investigated.

In vitro immunoresponsiveness in recipients of cadaveric renal allografts during ATG therapy.

Anti-human-T-cell-globulin (ATG-Fresenius) was given prophylactically in a fixed dose of 2mg per kg bodyweight to 32 renal allograft recipients in addition to a conventional immunosuppressive regimen, over a period of 20 days. ATG therapy resulted in a significant decrease of circulating T-lymphocytes, whereas B-lymphocytes remained unaffected. The mitogen reactivity during therapy paralleled the T-lymphocyte profile with a maximum decrease on day 8. With in vitro testing of ATG immunoresponsiveness it could be demonstrated that patients with rejection episodes after transplantation reacted differently from patients without signs of rejection. Actuarial patient and graft survival was about 5% higher in the ATG treated group of patients than in retrospective controls.

[Local and systemic antibody response after vaccination with 3 different types of vaccines against influenza. II. Neuraminidase inhibiting antibodies (author's transl)]. / Zur lokalen und systemischen Immunantwort nach Influenza-Schutzimpfung mit drei verschiedenen Vakzinetypen. II. Neuraminidasehemmende Antikörper.

Three types of inactivated bivalent influenza vaccines containing the A/Victoria/3/75 (A-Component) and B/Hongkong/8/73 (B-Component) antigens either as aluminium salt adsorbed whole virus (AlorbatTM, "A") and split virus (Begrivac STM, "B") or as fluid subunit (SandovacTM, "S") products were given to immunological homogeneous study groups of adults and children. The immune response was compared between the groups on the basis of systemic and local neuraminidase inhibiting (NI) antibody induction 4 weeks after vaccination. In evaluation of the serologic results the sea and nasal washings were tested in the ESSEN-NIT with use of the A/Eq(eq1)-VIC (N 2) recombinant antigen and the B/Hong kong/8/73 strain. The number of individuals (adults plus children) evaluated ranged from 33 to 35 per vaccine. The percentages of persons greater than or equal to 16 years old showing a significant (1.5 x, or greater) response to the A-component were 100%, 96% and 90%, respectively for the vaccine "A", "S" and "B"; the values for the B-component were 70%, 79% and 74%, respectively. The observed conversion rates in children ranged 70% to 100%. Local antibody formation was less pronounced, the percentages of significant conversions were scattered over a wide range from 13% to 80% yielding slightly better responses in children than adults. Taken altogether, the results of the trial indicate that the 3 vaccines studied induced appreciable concentrations of systemic antibodies to the neuraminidase antigen without significant differences between the vaccine types. This potency of the influenza vaccines to induce high titers of NI antibodies thus provides another marker for their immunogenicity and conceivably for their efficacy.