Immunological activity of a Proteus vaccine administered to volunteers simultaneously with a pyoimmunogen and adsorbed staphylococcal anatoxin

The comparative study of the immunological activity of Proteus vaccine prepared from soluble antigenic complexes was made after the immunization of volunteers with this vaccine used in the form of a single preparation and in combination with pyoimmunogen (Pseudomonas aeruginosa vaccine) and/or adsorbed staphylococcal toxoid. The injection of the vaccine in the form of a single preparation and in different combinations increased the ingestion of Proteus cells by neutrophils. The injection of Proteus vaccine simultaneously with pyoimmunogen and staphylococcal toxoid ensured the intensive phagocytosis of staphylococci. All combinations with Proteus vaccine, used in this investigation, stimulated the intensive formation of antibodies to Proteus vaccine strain and Re-glycolipid. Proteus vaccine introduced in combination with adsorbed staphylococcal toxoid essentially stimulated the synthesis of anti-alpha-staphylolysin.     

Systemic immunity of experimental animals immunized with cholera vaccines

The levels of antitoxic and vibriocidal antibodies in the sera of suckling rabbits after their parenteral immunization with cholera vaccine, cholera toxoid and a combination of cholera vaccine and toxoid were examined. Cholera vaccine induces intensive production of vibriocidal antibodies, and cholera toxoid, of antitoxic antibodies. The parenteral administration of the serum of rabbits immunized with cholera toxoid neutralized the action of cholera toxin in the small intestine of suckling rabbits. The complex preparation combines the properties of the corpuscular vaccine and the toxoid, inducing the production of both vibriocidal and antitoxic antibodies.     

Immunogenicity of a vaccine made from soluble Proteus antigens

Hemagglutinins with different specificity were determined in 270 subjects: of these, 101 were examined in the time course before and after immunization with Proteus vaccine prepared from soluble antigens. The preparation possessed pronounced immunological potency and stimulated the formation of antibodies to the vaccine strain, to heterologous Proteus strains and to the common antigens of Gram-negative bacteria. The combined scheme of the subcutaneous and local administration of the above-mentioned Proteus vaccine ensured an increase in the synthesis of IgM and IgA in patients with Proteus wound infection. Active immunization ensured an essential rise in the level of hemagglutinins to Re-glycolipid in donors and oncological patients not infected with Proteus, but did not ensure the statistically significant shifts in the antibody level to Re-glycolipids in patients with chronic Proteus infection.     

Comparative study of the immunoglobulins and specific antibodies in the blood of rabbits immunized with ADTP vaccine and ADT-anatoxin with normal and reduced antigen contents

Adsorbed DPT vaccine and adsorbed DT toxoids with normal and reduced antigen content were used for the immunization of rabbits. The levels of IgM and IgG and the dynamics of antibodies to diphtheria and tetanus toxins and to Bordetella pertussis in the blood sera of the animals were studied in the postvaccinal period (on days 15 and 34). This study revealed that the reduction of the antigen content of adsorbed DT toxoid to 5 Lf of diphtheria toxoid and 5 binding units of tetanus toxoid did not decrease the capacity of the preparation for increasing the levels of IgG and IgM, antibodies to diphtheria and tetanus toxins in the sera of the rabbits. The reduced content of these toxoids in adsorbed DPT vaccine did not affect its capacity for inducing the enhanced synthesis of IgG, antibodies to diphtheria and tetanus toxins, while the production of IgM and IgA remained unchanged. At the same time an increase in the titers of antibodies to B. pertussis in the animals was less pronounced than that observed after the injection of commercial adsorbed DPT vaccine. Additional investigations are necessary in order to establish the protective potency of the pertussis component in adsorbed DPT vaccine with the reduced content of toxoids and to find out the optimum antigenic composition for this preparation.     

The characteristics of the protective and antigenic activities of purified staphylococcal anatoxin in trials with mice of different genotypes

The protective potency of purified staphylococcal toxoid by the survival rate of immunized mice challenged with the culture of Staphylococcus aureus strain L-1726 and the antigenic properties of the toxoid, determined by the level of antitoxin in the blood of mice and by the intensity of cell-mediated immunity in the spleen-cell migration inhibition test, were studied. The experiments were made on CBA and C57BL/6 mice. Purified staphylococcal toxoid was shown to possess antigenic and protective properties in a wide range of doses between 0.15 and 15 binding units per mouse. The protective effect of the toxoid in CBA mice was manifested in the presence of circulating antibodies and cell-mediated reaction or only in the presence of the toxoid. In C57BL/6 mice the protective effect of the toxoid was less pronounced and appeared in combination with the induction of cell-mediated immunity in the presence of an extremely low antibody level (0.062 I.U.).     

Protective effect of the aerosol immunization of mice with the polycomponent vaccine Immunovac VP-4 after the challenge of the animals with Klebsiella pneumoniae virulent strain

Used four schemes of the administration of the preparation with different time of the exposition of the animals in an aerosol chamber were tested with their subsequent intraperitoneal challenge with K. pneumoniae virulent strain K16. Irrespective of the number of immunization courses, the administration of the preparation made at intervals of 1 day, or daily, did not ensure any protective effect, but only led to an insignificant increase in their survival time in comparison with nonimmunized animals. After intervals between immunizations were increased to 3 days the protective effect of aerosol immumization was obtained (the survival rate was 65-80 % and considerably differed from that of the controls). The protective effect of aerosol immunization thus obtained was comparable with the effectiveness immunization made in a single subcutaneous injection. Aerosol immunization resulted in low antibody titers to the antigens contained in the vaccine, while after a single subcutaneous injection high antibody titers to Klebsiella and Proteus antigens were detected. The antigen-stimulated blast transformation of spleen lymphocytes in mice subjected to aerosol immunizations in 5 exposures was high. After subcutaneous immunization significant changes in such characteristics were detected on day 15. The data thus obtained were indicative of good prospects in the development Immunovac VP-4 as the medicinal form intended for use in aerosols.     

The antigenic activity of vaccines made from opportunistic microorganisms in an experiment to immunize animals by oral and combined methods]

The results of the study of the antigenic activity of multicomponent vaccine consisting of staphylococcal, Klebsiella, Proteus, Escherichia coli antigens and staphylococcal monovaccine, introduced into rabbits and guinea pigs by different routes, are presented. As shown in this study, the multicomponent vaccine introduced orally in 5 administrations stimulated the production of antibodies to all components, but the intensity of antibody formation to each of them was different. Antibodies to E. coli antigen were found to be at the lowest level. Staphylococcal antigen, introduced orally both as the component of the multicomponent vaccine and as the monovaccine, ensured pronounced stimulation of the production of antistaphylococcal antibodies, not lower than that observed after subcutaneous injection. The comparative study of the activity of the multicomponent vaccine introduced by combined routes, oral-subcutaneous and subcutaneous-oral, showed the advantage of the former one.     

Immunoprevention of staphylococcal infections at an industrial enterprise

The immunogenicity, immunological and epidemiological effectiveness of the subcutaneous, enteral and combined immunizations of the workers at a steel plant with staphylococcal toxoid has been studied. The subcutaneous injection of the adsorbed toxoid in a dose of 0.2 ml by means of the jet injector, model, was accompanied by moderate reactogenicity (the frequency of local reactions was 26.8%, and the frequency of systemic reaction 18%) and produced 4-fold increase in antitoxin titers and 12-fold decrease in the morbidity rate of staphyloccal infection. Enteral immunization in 3 administrations proved to be nonreactogenic and only slightly effective (antitoxin titers increased more than 2-fold, morbidity rate fell 2-fold). Combined immunization (subcutaneous and enteral) with the toxoid, preceded by the injection of gamma globulin, reduced the frequency of reaction 2- to 3-fold and stimulated antitoxin production (the titer increased 8-fold), thus decreasing the morbidity rate of staphylococcal infection 3.1-fold.     

A comparative evaluation of the immunological efficacy of ADPT vaccine and ADT-M anatoxin in the immunization of children against diphtheria and tetanus

Comparative study of the immunological effectiveness of adsorbed diphtheria-pertussis-tetanus (DPT) vaccine and adsorbed diphtheria-tetanus toxoid with reduced antigen content (adsorbed DT toxoid R) in the immunization of children, carried out in accordance with the vaccination schedule, was made. Immune response to the injection of adsorbed DPT vaccine was higher than after immunization with adsorbed DT toxoid R, as evidenced by antibody titers. It was probably due to differences in the number of injections constituting the course of immunization: it consisted of 3 injections and 1 booster injection for adsorbed DPT vaccine and 2 injections and 1 booster injection for adsorbed DT toxoid R. Immunization with adsorbed DPT vaccine produced immunity which was retained for a longer period. These results are indicative of the expediency of the primary immunization of children with adsorbed DT toxoid R introduced in three injections in order to ensure more stable and prolonged postvaccinal (mainly antidiphtheria) immunity.     

The effect of immunotherapy with cell-free vaccines made from the antigens of opportunistic microorganisms on the dynamics of DNA antibody formation]

The sera of patients subjected to immunotherapy with staphylococcal vaccine and with multicomponent vaccine (i.e. the mixture of the antigenic preparations of Staphylococcus aureus, Klebsiella pneumoniae, Proteus vulgaris, Escherichia coli) were studied by the method of the enzyme immunoassay on the basis of cattle spleen DNA. Immunotherapy with staphylococcal vaccine was given to patients with dermal diseases, chronic obstructive bronchitis and pulmonary abscess. Multicomponent vaccine was introduced to patients with the infectious allergic form of bronchial asthma, moderate or severe. Immunotherapy with both preparations under study was shown to produce no accumulation of antibodies to native and denatured DNA.     

Immunostimulating activity of polycomponent vaccine "Immunovac-VP-4" and grippol after their combined administration

The experimental study of the immunostimulating activity of therapeutic bacterial polycomponent vaccine VP-4 and prophylactic vaccine grippol, introduced both separately and in combination, on mice infected with Salmonella typhimurium, used as a model. Both preparations were found to produce an immunomodulating effect. The combined subcutaneous injection of VP-4 and grippol did not decrease their immunostimulating activity, but their separate administration at an interval of 14 days resulted in essential decrease in the protective activity of each of these two preparations. As shown on the model of Klebsiella infection in mice, challenged 4 weeks after immunization, VP-4 ensured the survival of 78.6% of mice, while after the injection of grippol their survival rate was not different from that of the group of intact animals. The evaluation of the immunostimulating activity of these preparations under the conditions of the prophylaxis of influenza and acute respiratory infections in organized groups of children revealed that the use of VP-4 alone or grippol in combination with VP-4 considerably decreased the number of secondary bacterial complications in children.     

Passive protection of mice with the 19 S and 7 S fractions of anti-pertussis sera in experiment.

Protective activity of anti-persussis rabbit and mouse sera and 19 S and 7 S fractions obtained from these sera was investigated in the test of passive protection of mice on a model of pertussis meningoencephalitis. The method of simultaneous intracerebral administration of the serum or fraction with live culture of a virulent B. pertussis strain was used. Hyperimmune rabbit serum containing mercaptoethanol-resistant agglutinins in a high titre was found to have the most pronounced protective effect. Serum of mice, collected 14 days after single immunization of the animals, did not show any protective properties. A small amount of protective activity was observed in the serum collected on the 30th day after a single administration of the vaccine. A sharp increase in the protective activity of the serum was observed after double immunization of mice. Correlation was found between the increase in the titre of agglutinins (in particular of 7 S antibodies) and the protective activity of the serum. Protective properties of 19 S and 7 S fractions isolated from immune rabbit and mouse sera by the method of gel filtration were investigated. Both fractions were found to possess protective properties, but fraction 7 S was more active than fraction 19 S.     

Evaluation of reactogenicity and immunogenicity of Bubo-M, the Russian combined vaccine for immunization of adults against diphtheria, tetanus and viral hepatitis B

Bubo-M, the first Russian associated vaccine, was found to have low reactogenicity and high immunogenic potency. The frequency of postvaccinal reactions in the group of persons immunized with Bubo-M (20%) appeared to be considerably lower than among persons who received the combined injection of adsorbed DT toxoid with reduced antigen content and vaccine against hepatitis B (47.7%). Following the course of vaccination the level of anti-HBs considerably exceeded the protective level. Immune response to the diphtheria and tetanus components of Bubo-M exceeded that observed after immunization with absorbed DT toxoid with reduced antigen content (p < 0.05).     

Comparative evaluation of the immunological activity of new typhoid vaccines with established prophylactic effectiveness (data from a controlled experiment)]

The authors present the results of studying the immunological efficacy of a dry alcoholic typhoid vaccine enriched with S. typhi Vi-antigen in the assessment of this vaccine in controlled epidemiological trial during the immunization of children aged 7--8 years. O- and Vi-antibodies were tested in the reaction of hemagglutination, H-antibodies--in the agglutination reaction with the microbial diagnostic agent, the properties of antibodies--in a test with cystein, and bactericidal properties of the sera--against the virulent S. typhi strain. Examination of 355 coupled sera obtained before and 3 weeks after the immunization demonstrated a high level of Vi-(1:47) and of the O-(1:580) antibodies and high bactericidal properties of the sera in persons vaccinated with the alcoholic vaccine enriched with the S. typhi Vi-antigen. The results obtained and the data on the formation of prolonged immunity following a simgle immunization suggested that a high protective effect was caused by a combined action of the O- and Vi-antigens contained in the vaccine in optimal doses.     

Protective properties of anatoxin obtained from a homogeneous preparation of Pseudomonas aeruginosa exotoxin A

The protective properties of formulated toxoid obtained from the highly purified preparation of P. aeruginosa exotoxin A have been studied in the test of the active immunization of mice. The study has revealed that the preparation when introduced in 1 or 2 injections in a dose of 15 micrograms, shows faint protective potency with respect to P. aeruginosa strains differing in virulence. Immunization with this toxoid in 3 and 4 injections has been found to ensure 60-100% and 50-60% protection of mice infected with P. aeruginosa toxigenic and proteolytic strains respectively. Immunization with toxoid has been found to induce the appearance of short-term antibacterial immunity which loses its capacity to protect the immunized animals, challenged with both toxigenic and proteolytic P. aeruginosa strains, as early as on day 28. The immunization of mice with toxoid in 4 injections has been shown to induce the development of antitoxic immunity capable of neutralizing up to 150 LD50 of purified exotoxin A.     

Experimentally determined safety and immunological activity of vaccine based on antigens isolated from Pseudomonas aeruginosa in medium K-4

The safety and immunological activity of P. aeruginosa vaccine were experimentally evaluated. The vaccine was prepared on the basis of the antigens of P. aeruginosa extracellular slime which was accumulated in medium K-4, obtained with the use of original technology. The immunization of animals with P. aeruginosa vaccine induced the synthesis of antibodies. The introduction of the vaccine in 2 or 3 injections resulted in a high level of antibody formation, differing with the use of various strains. Hyperimmune sera, obtained by the multiple immunization of rabbits with P. aeruginosa vaccine, ensured high protection of mice from P. aeruginosa infection. The vaccine proved to be safe when evaluated in experiments of acute and chronic toxicity, made on laboratory animals.     

Immune response in adult immunized with adsorbed DT-M anatoxin with reduced antigen content and Imovax-DT-adulte vaccine

The comparative study of immune response after immunization of adults with adsorbed DT toxoid with reduced antigen content and Imovax-DT-adulte vaccine, as well as the safety of these preparations, was made. The study revealed that immunization of adults with adsorbed DT toxoid having reduced antigen content, made in two injections, and the injection of Imovax-DT-dulte vaccine, as well as the successive injection of these preparations, produced the same the levels of antitetanus immunity. Antidiphtheria immunity, evaluated by the number of seroconverted to diphtheria persons following two injections immunization was similar for the two preparations, while the level of antidiphtheria antibodies was higher in persons immunized with adsorbed DT toxoid. The immune stratum index was rather high among persons aged 16-29 years. This age group exhibited the highest number of persons, seropositive to both diphtheria and tetanus. Both vaccine preparations, adsorbed DT toxoid with reduced antigen content and Imovax-DT-adulte vaccine, were found to be equally capable of inducing autoimmune reactions in the vaccinees, detected by laboratory methods.     

The immunomodulating properties of a diphtheria bacterial vaccine in in vitro experiments

In this investigation lymphocytes sensitized with Corynebacterium diphtheriae antigens obtained from carriers and convalescents were used. The new diphtheria bacterial vaccine Codivac, in contrast to other comparable preparations (diphtheria toxoid, staphylococcal toxoid, staphylococcal vaccine, levamisole), was found to produce a more direct effect by modulating the levels of T-lymphocytes, depending on their initial levels in the patient. Codivac, together with other preparations, can be used for the study of the problems of immunostimulation and immunocorrective therapy.     

Proteus peritonitis-bacteremia in mice--a model for studying postvaccinal Proteus immunity

The dynamics of the formation of postvaccinal immunity after immunization with preparations obtained with the use of hydroxylamine (HA) preparations from Proteus strains of different O serogroups, Salmonella minnesota Re-mutant and the common antimicrobial antigen isolated from Escherichia coli 14 has been studied on mice with Proteus peritonitis-bacteremia used as a model. The study has revealed that intraperitoneal immunization with Proteus HA preparations stimulates the phagocytic activity of peritoneal mononuclear cells in mice and induces an increase in the titers of specific O antibodies. Proteus antigens ensure the formation of anti-Proteus immunity, preventing the death of the animals from peritonitis-bacteremia. The protection of mice from such infection resulting from the injection of the common antigens of gram-negative bacteria is considerably less. These data are indicative of the possibility of using Proteus peritonitis-bacteremia as a model for the study of the protective potency of Proteus vaccines.     

Immunomorphologic study of experimental enteric anc combined vaccination against cholera]

As a result of the enteral and combined subcutaneous-enteral immunization of adult rabbits with cholerogen toxoid and the specific fraction of chemical cholera vaccine in tablets immunological transformation occurred in the organism and a "protective" barrier consisting of antibody-containing cells was formed in the intestine on days 3-5. The combined method of immunization with cholera vaccine proved to be essentially as effective as enteral immunization in 2 administrations.