Search

The influenza virus isolation in embryonated chicken eggs was possible early in 1930er years and allowed the influenza vaccine production. Most influenza vaccines were derived from this, but actually new virus cell culture methods are established. For better tolerability, influenza vaccines include only antigen proportions (split- and subunit vaccines) but with the disadvantage of minor vaccine efficacy. This was compared with the addition of adjuvants. Aluminium salts are used for many decades and still in use to enhance the effect of vaccines. New formulations are MF59, AS03, AS04 or toll- like receptor-agonists. Also virosomal formulations and "ISCOMs"(Immune Stimulating Complexes) are newly designed and compromises enhanced immune reactions. Actually a broad range of various influenza vaccines exist and are available for a very different group of patients (which depends on physical conditions, age, immune status or allergies)., (© Georg Thieme Verlag KG Stuttgart · New York.)

Apart from live spore vaccines with a certain amount of residual virulence for various animal species, there are two acellular protein vaccines for immunoprophylaxis against anthrax in humans. For ethical reasons there are no experimental data available on the efficacy and duration of the immunity they induce in men. Their efficacy was evaluated in laboratory animals, mainly rabbits and rhesus monkeys. Furthermore, it is well known that these vaccines elicit only partial protection in guinea pigs and almost no protection in mice against a challenge with fully virulent spores of Bacillus (B.) anthracis. Other disadvantages are the high amount of boosters necessary to elicit and to maintain a protective immune response, the variability in the composition of bacterial culture supernatants used for production, and the appearance of clinically relevant side effects. Therefore, there is ongoing work worldwide to improve the existing vaccines by substitution with recombinant antigens and to develop new vaccines on the basis of recombinant bacterial or viral live vectors, DNA-vectors, and by addition of new adjuvants. Special attention is given to supplementing the existing toxoid-vaccines with an anti-bacterial component.

In the past years, enormous efforts have been undertaken to develop vaccine strategies against cancer. The aim is to have the immune system generate what are called killer cells that can specifically recognize the tumor. The surface of tumor cells contains MHC/HLA antigens which present short-chain peptides of tumor specific antigens. A large number of these oligopeptide antigens have been characterized in recent years. They are now available for use as tumor-specific vaccines. The problem is, however, that the immune response of producing T killer cells is very inefficient when these oligopeptide antigens are injected. As the physiological function of these killer cells virus-infected cells, a process associated with substantial tissue damage, the immune system has learned to use these killer cells with reticence over the course of evolution, in other words, when the life of the host is threatened. This does not happen until pathogens start to spread via lymphogenous or hematogenous pathways. And then it takes a certain amount of time after the invader is present for replication to take place. Since the oligopeptide antigens used as vaccines have a very short half-life in the tissue, not enough of them get to the lymph nodes and stay there for enough time to efficiently induce an immune response. Using a mouse model, we were able to show that the efficiency of the vaccine can be increased a million-fold by directly injecting the vaccine into a lymph node or the spleen which imitates lymphogenous or hematogenous spread. The efficiency of the "inactivated vaccine" can be enhanced even more by continuous administration of the vaccine over several days, simulating an especially dangerous virus replication. The evidence gathered in this mouse model was transferred to a clinical trial. The melanoma-specific inactivated vaccine is infused directly into a lymph node of tumor patients. The infusion is continued for several days. Booster vaccines are given every two weeks.

Current influenza vaccines in use at present are predominantly inactivated virus vaccines. The vaccines currently in use are designated whole-virus vaccines, split virus vaccines or subunit vaccines. In Europe, two new types of influenza vaccines have reached the commercial introduction. One is produced in Italy and uses the new adjuvant MF59 to enhance the immune response. The other type is produced in Switzerland and uses phosphatidyl choline (lecithin) liposomes as surface antigen carriers.

Basic Problem and Objective: The immune response to parenteral antigens is reduced in persons without spleen. The seroconversion rate was measured after application of a new type of vaccine against hepatitis A (immunopotentiating reconstituted influenza virus virosome [IRIV]) in patients who had undergone a splenectomy after trauma., Patients and Methods: 26 patients (23 men and 3 women, mean age 34.9 +/- 9.7 [25-65] years) with anti-hepatitis A virus (HAV) antibody titres < 20 mIU/ml (maximally 17 mIU/ml) were given a single dose of 0.5 ml of the IRIV hepatitis A vaccine 1 to 14 (mean 9.4) years after splenectomy. Immediately after the immunisation and 14 and 28 days afterwards anti-HAV titres were determined. A titre rise to < 20 mIU/ml was counted as seroconversion. At the first and last titre measurement immunoglobulins, neopterin and beta-microglobulin levels were also measured as additional markers., Results: The seroconversion rate was 69.2% (18/26) after 14 days (geometric titre mean: 39 mIU/ml) and rose to 88.5% (23/26) after 28 days (geometric titre mean 74 mIU/ml). Seroconversion occurred in the three nonresponders after a second dose of the vaccine. All measurements of the immunological markers were within normal limits., Conclusion: A single dose of a new type of vaccine against hepatitis A confers adequate protection even in those persons who had a splenectomy.

Development of humoral precipitating antibodies against Campylobacter spp. in chickens. The development of precipitating antibodies in chickens was examined by two-dimensional immunodiffusion test after immunization with a formol inactivated vaccine and after subcutaneous and oral application of different live campylobacter serovars. The supernatant of bacterial cells after sonication and centrifugation was used as an antigen in the agar-gel precipitin test. Antisera against different campylobacter serovars showed a high percentage of cross-reactions. In chickens immunized with an inactivated vaccine at an age of 1, 2, 3, 4 and 7 weeks, precipitating antibodies could be demonstrated for the first time at 7 days p.i. Except for 1-week-old birds, sera from the other groups reacted positively at 14 days p.o. After subcutaneous duplication of live organisms to 4-week-old chickens, antibodies could already be demonstrated at 4 days p.i. later in part of the experimental groups. No interrelation could be detected between antibody titers, measured by enzyme-linked immunoabsorbent assay (ELISA), from precipitating sera, as well as from those from non-precipitating sera. Precipitating antibodies and antibody titers in the ELISA were examined in sera from groups of birds infected at an age of 1, 2, 3, 4 and 7 weeks. During the Campylobacter excretion period, a distinct peak of antibody titers occurred in 1- and 7-week old birds, whereas other groups showed a steady increase in titers. Precipitating antibodies were only found in 1- and 2-week-old chickens.

Criteria for the selection of vaccines against Newcastle disease are presented. Questions related to safety and potency are considered. Intramuscular vaccination of 23 young storks with an inactivated vaccine is described. All storks tolerated the vaccination without recognizable undesired side-effects. The young storks reacted with the production of serum antibodies three weeks post vaccination. No data is yet available on the duration of the persistence of humoral antibodies. The vaccinated mature storks were free of detectable antibodies at the day of vaccination and five months later.

Acellular pertussis vaccines contain antigen components of B. pertussis, usually lymphocytosis promoting factor (LPF) which is also called pertussis-toxin (PT) or pertussigen, filamentous hemagglutinin (FH) and, eventually, agglutinogens 2 and 3. Acellular vaccines are being used in Japan since 1981. Several Phase II studies have been performed and showed a better tolerability than whole cell vaccines and antibody responses of at least equal magnitude. In some of these studies good protection rates were observed. The latter were not satisfactory in a Phase III study in Sweden. This study, however, might cause some criticism in as much as only 2 vaccine doses were given and a control group with whole cell vaccine was missing. Moreover, the significance of bacterial infections in vaccinated children is doubtful, similar observations have not been made in other trials nor in Japan since introduction of the vaccine in 1981. Preliminary results of our own study with a newly developed acellular vaccine which has been permitted by the Austrian Drug Commission have shown good tolerability.

The efficacy and safety of a vaccination during anaesthesia was examined in 20 puppies from 8 litters of one kennel. The animals were vaccinated in a state of reflex-free anaesthesia (neuroleptanalgesia in combination with halothane, nitrous oxide and oxygen). 20 puppies from the same litters were used as controls. A parvovirus living vaccine (Canimed) and a rabies vaccine from inactivated viruses (Rabisin) were used for the vaccinations. The titers of neutralizing antibodies against rabies virus were significantly lower in the group of anaesthetized animals compared to the control group on the 10th and 20th day p.vacc. The average titers of antibodies against parvovirus of both groups, however, do not allow any statistically significant statements. It is nevertheless remarkable that 6 of the anaesthetized puppies (three different litters) showed no increase in antibodies. The results of the investigations lead to the recommendation not to vaccinate anaesthetized puppies. The risk of reducing the efficacy of vaccinations with vaccines from inactivated agents is greater than with living vaccines.

The efficacy of a newly developed polyvalent bacterial lysat vaccine "Infectvac" was tested in experimental studies in animals. It was shown that a local application (oral, aerogenic) prevent the animals from a lethal bacterial (S. pneumoniae) or viral (A/PR/8/34) infection. In first clinical trials a good compatibility of the drug was demonstrated.

360 volunteers were recruited for the investigation from a homologous collective. 174 were immunized parenterally with "Influmun" from SSW Dresden, GDR. 176 volunteers were immunized twice orally with an interval of 60 days with an influenza vaccine inactivated by x-ray using enteric-coated capsules. In an interval of six months ARI-symptoms were investigated. Between 13th and 17th week 1988 an increased ARI-morbidity in the Greifswald-region was observed in which influenza A viruses were involved. In comparison with 312 non-immunized persons of the same age, sex and living area the immunized volunteers of the two groups showed 83.4% less sickness days. 30 persons of the non-immunized group got ill for totally 217 days, whereas only nine persons of the two immunized groups were put on the sicklist for totally 36 days. No significant differences concerning the occurrence and duration of acute respiratory infections (ARI) between the two differently immunized groups could be observed.