Effect of lincomycin and staphylococcal vaccine on the course of experimental staphylococcal sepsis

Therapeutic efficacy of lincomycin used alone and in combination with inactivated staphylococcal vaccine and the effect of these agents on synthesis of antibodies and their content in blood serum were investigated. Lincomycin was shown to inhibit septic processes in the host. After its administration the number of the pathogens in the blood and organs markedly decreased. At the same time, lincomycin lowered antibody synthesis in the lymphoid organs and the content of alpha-antitoxins in blood serum. The use of lincomycin in combination with inactivated staphylococcal vaccine promoted an increase in the number of the antibody forming cells in the spleen and lymph nodes and the content of the antibodies to the staphylococcal alpha-toxin in blood serum of the animals with staphylococcal sepsis.     

The preventive effect of adjuvant-free administration of TNF-PADRE autovaccine on collagen-II-induced rheumatoid arthritis in mice

Adjuvants are necessary to elicit high titers of antibodies in vaccine-immunization procedures. We previously developed a mouse tumor necrosis factor-α (TNF-α) autovaccine (mTNF-PADRE) capable of inducing anti-TNF-α antibodies. In this study, we investigated the therapeutic effect of adjuvant-free administration of the autovaccine on collagen-type-II-induced rheumatoid arthritis (CIA) in mice. Our results showed that the vaccine could ameliorate the symptoms of CIA in mice. In addition, this study suggests that it is possible to control the antibody levels in mice immunized with mTNF-PADRE without adjuvant.     

Protective efficacy of combined administration of the multicomponent vaccine and the immunomodulator myelopid in experimental infections in mice

The influence of myelopid (MP) on the protective activity of polycomponent vaccine VP-4 prepared from the antigens of opportunistic bacteria was studied on experimental infections of mice, caused by Klebsiella pneumoniae, Salmonella typhimurium and Staphylococcus aureus. In staphylococcal and Klebsiella infections the joint administration of vaccine VP-4 and MP produced more pronounced protective effect than each of these preparations, introduced alone. The protective action of vaccine VP-4 was specially enforced by MP in cases of local staphylococcal infection. Recommendations on the joint use of two or more immunomodulating agents are possible only on the basis of the experimental substantiation of their effect in definite infections.     

Sensitizing and protective activity of a staphylococcal vaccine made of water-soluble antigens, depending on the method and schedule of administration

An experiment on guinea pigs immunized with staphylococcal vaccine prepared from water-soluble antigens revealed that the degree of developing sensitization and specific resistance was essentially determined by the method and schedule of the administration of the preparation. The intranasal administration of the vaccine induced a lesser degree of sensitization in comparison with its subcutaneous injection. The optimum response to the administration of the vaccine (a low sensitization level and a high degree of protection from infection) was observed in the animals immunized first intranasally and then by subcutaneous injection. The subcutaneous injection of the preparation in combination with its subsequent intranasal application induced a more pronounced degree of sensitization and a lesser degree of protection from infection.     

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.     

The effect of repeated administration of staphylococcal immune preparations on the development of local staphylococcal infection in mice

The study is concerned with the effect of repeated administration of staphylococcal immunopreparations on the development of a suppurative-inflammatory focus in the foot of the mouse. Subcutaneous administration of large doses of the antigenic complex of the staphylococcus (ACS) obtained by aqueous extraction, antiphagin and native anatoxin failed to induce an increase in sensitivity to staphylococcus. In some cases, the extent of development of the suppurative-inflammatory focus in the mice which had been given these preparations was less than in the control; this is suggestive of their protective effect. When comparing, on this model, the ACS preparations and corpuscular vaccine produced from poorly and highly virulent strains, we observed a more pronounced protective effect in the preparations from the poorly virulents strains. The extent of oedema was greater than in the control when adsorbed anatoxin was administered. The administration of staphylococcal preparations with a therapeutical purpose after staphylococcus infection caused a significant decrease in the size and intensity of manifestation of the suppurative-inflammatory focus in the foot. The model of limb oedema enabled us to reveal the sensitizing and protective effect of the preparations under study.     

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.     

Postvaccinal reactions to the administration of a dried staphylococcal vaccine made from water-soluble antigens

An unequivocal regularity in local and systemic reactions to multiple (in 5 injections) administration of lyophilized staphylococcal vaccine prepared from water-soluble antigens has been established in patients and in healthy adults: the number and intensity of reaction decreased after each subsequent injection. A similar tendency has been observed in the vaccinees who were examined for their IgE levels. These data are indicative of the desensitizing action of the vaccine.     

Effect of antibiotic therapy and vaccine therapy on the phagocytic reaction in mice infected with Staphylococcus

The time course of changes in the activity, intensity and completeness of phagocytosis with leukocytes of the peritoneal exudate was studied on mice with experimental staphylococcal infection treated with rifampicin, lincomycin and inactivated staphylococcal vaccine used alone or in combination. It was shown that immunization of the animals with inactivated staphylococcal vaccine promoted stimulation of the phagocytic defense. Rifampicin and lincomycin applied therapeutically induced a decrease in the activity, intensity and completeness of phagocytosis. It should be noted that rifampicin had a less pronounced inhibitory effect than lincomycin. The combined use of vaccine and antibiotics with therapeutic purposes promoted an increase in phagocytosis as compared to the use of the antibiotics alone. The combined therapy sometimes resulted in completeness of phagocytosis making it reach the control values (the 10th and 15th days, rifampicin and vaccine). It should be noted that a more pronounced stimulation of the activity, intensity and completeness of the phagocytosis was observed with the use of the combination of rifampicin and the vaccine.     

Immunogenic and protective effects of an oral DNA vaccine against infectious pancreatic necrosis virus in fish

DNA vaccines and oral DNA-based immunotherapy against infectious pancreatic necrosis virus (IPNV) have scarcely been studied in salmonid fish. Here, a vector with the capsid VP2 gene inserted was encapsulated in alginate microspheres to avoid the aggressive gastrointestinal conditions experienced following oral administration. Alginate microspheres were effective to protect the pDNA encoding VP2, which was expressed early in different organs of the vaccinated trout and that persisted for at least 60 days. The vaccine induces innate immune responses, raising the expression of IFN more than 10-fold relative to the fish vaccinated with the empty plasmid, at 7 and 15 days post-vaccination. Likewise, maximal expression of the IFN-induced antiviral Mx protein was recorded 15 days post-vaccination and neutralizing antibodies were also detected after 15 days, although their titre rose further at 21 days post-vaccination. Protection was high in the immunized fish, which showed around an 80% relative survival when challenged 15 and 30 days after vaccine delivery. Very low viral load with respect to the control group was detected in the vaccinated fish that survived 45 days after challenge. Thus, this study demonstrates the potential of the encapsulation technique for IPNV-DNA vaccine delivery and the relevance of the IPNV-VP2 gene for future plasmid constructs.     

Effect of antibiotic and vaccine therapies on the succinate dehydrogenase and phosphatase activity of liver cells of mice infected with Staphylococcus

Changes in the activity of succinate dehydrogenase (SDH), total and acid phosphatase (TP and AP) were studied in treatment of laboratory animals with rifampicin, lincomycin and with inactivated staphylococcal vaccine used alone or in combinations. It was shown that immunization of the animals with inactivated staphylococcal vaccine under conditions of experimental staphylococcal infection promoted stimulation of the enzyme activity. Rifampicin and lincomycin used for the treatment of such animals lowered the activity of the enzymes. The suppressing effect of the antibiotics increased with an increase in the period of their use. It should be noted that the inhibitory effect of rifampicin on the activity of SDH, TP and AP was less pronounced than that of lincomycin. The combined use of the vaccine and antibiotics for the treatment of the animals promoted an increase in the enzyme activity as compared to the use of the antibiotics alone. Sometimes the activity of SDH, TP and AP reached the control levels in such animals or the levels observed in the animals treated with the vaccine alone. Stimulation of the enzyme activity was more pronounced when the vaccine was used in combination with rifampicin.     

Morphological changes in experimental infection in guinea pigs under the influence of prodigiozan and S-methylmethionine]

The effect of prodigiozan and S-methylmethionine on the level of histomorphological changes in the organs and tissues of guinea pigs with experimental typhoid fever, dysentery and staphylococcal infections, as well as the effect of prednizolone with respect to dysentery and staphylococcal infections were studied. In the control animals the highest histomorphological changes were observed on the 4th day after the infection in the liver, kidneys and spleen. In the animals with staphylococcal infection such changes were also observed in the lung tissue. In the animals treated with prodigiozan or S-methylmethionine in a dose of 20 mg or 0.3 ml of a 5 per cent solution respectively simultaneously with or 2 days after the infection the changes in the organs were less pronounced than those in the control. Under the effect of prednizolone used in a dose of 10 mg according to the same schedule the inflammatory-dystrophic changes in the internal organs of the animals with dysentery and staphylococcal infections were much higher as compared to the control.     

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.     

Apudocytes in experimental cholera vaccination

The morphofunctional state of apudocytes in the gastrointestinal tract and immunocompetent organs (spleen, mesenteric lymph nodes) of mice immunized with chemical bivalent cholera vaccine was studied. The study revealed that the APUD system of the intestine and the argyrophil elements of the immunocompetent organs of white mice gave a response to the oral administration of commercial cholera vaccine. The reaction of the APUD system of the gastrointestinal tract was manifested by a significant increase in the number of apudocytes and their greater synthesizing activity in the immunized animals during the period of maximum immunological transformation of the macroorganism. The immunization of mice with Vibrio cholerae facilitated the maintenance of homeostasis in the macroorganism and prevented appearance of morphological disturbances in its organs and system after subsequent challenge with V. cholerae.     

Preventive properties of the blood sera from persons vaccinated with a Proteus vaccine made from soluble antigen complexes

In experiments of the passive protection of mice the protective properties of sera obtained from humans before and after their immunization with Proteus vaccine used as a monopreparation or in combination with staphylococcal toxoid and/or pyoimmunogen were studied. When introduced in a single subcutaneous injection, Proteus vaccine prepared from soluble antigenic complexes ensured an increase in the protective properties of sera. The second injection of the vaccine essentially enhanced the protective potency of the sera of the immunized donors. The therapeutic injection of Proteus vaccine ensured the essential increase of the protective properties of the sera. This increase could be experimentally detected within at least 25-30 days from the beginning of immunization. The immunization of volunteers with Proteus vaccine in combination with pyoimmunogen and adsorbed staphylococcal toxoid ensured the maximum increase of the protective properties of their sera.     

Immunological mechanisms of specific hyposensitization in allergic diseases of an infectious nature.. I. Hyposensitization with autovaccine]

Immunological processes in 17 patients with infectious allergic bronchial asthma accompanied by chronic respiratory tract infection were studied in dynamics resulting from the hyposensitization of the patients with autovaccine. Specific sensitization was shown to produce stable clinical remission. The therapeutic effect of this method was ensured by a simultaneous hange in non-specific cellular and humoral immunity. A stable therapeutic effect was observed gainst the background of activated immunological processes and weakened sensitization.     

The reactogenicity and efficacy of a dried cell-free staphylococcal vaccine in treating chronic bronchitis]

The data obtained in the controlled trial of the immunotherapy of chronic bronchitis (CB) patients with lyophilized acellular staphylococcal vaccine developed at the Mechnikov Research Institute for Vaccines and Sera (USSR Acad. Med. Sci.), Moscow, are presented. The patients were divided at random into two groups; of these, one group received the vaccine and the other, placebo (0.9% sodium chloride solution). The preparations were injected subcutaneously simultaneously with traditional treatment. The vaccine was well tolerated by the patients. In the blood of the patients receiving the vaccine, in contrast to those receiving placebo, a significant increase in the level of specific antibodies determined in the passive hemagglutination test and IgG was noted. When following the remote consequences of the disease for a year after the course of immunotherapy, a significant decrease in the occurrence of aggravations, an increase in the duration of remission and a decrease in the duration of sick leaves were registered. These data indicate that the immunotherapy of CB with lyophilized acellular staphylococcal vaccine is a promising method of preventing relapses.     

Assessment of the immune status of chronic bronchitis patients in the remission phase during prophylactic treatment with levamisole and staphylococcal vaccine

The work presents the results of the study of the immune status in 18 patients with chronic bronchitis at the stage of remission, subjected to prolonged prophylactic treatment with the inhalations of levamisole solution, and in 16 patients receiving the inhalations of staphylococcal vaccine. These results indicate that the inhalations of levamisole have proved to be more effective than the inhalations of staphylococcal vaccine. In patients treated with levamisole an essential decrease in the ratio of theophylline-resistant to theophylline-sensitive E-rosette-forming lymphocytes has been noted. The determination of the sensitivity of lymphocytes and neutrophils to incubation with levamisole by means of the rosette-formation test makes it possible to prognosticate, taking into account the initial level of spontaneous E-rosette formation of these cells, the effectiveness of the prophylactic treatment of patients with chronic bronchitis. The determination of the sensitivity of the cells to incubation with staphylococcal toxoid is ineffective for the prognostication of the result of the treatment of such patients with staphylococcal vaccine.     

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.     

Immune response following administration of multicomponent vaccine VP-4 in elderly patients

The dynamics of immunological characteristics after the administration of polycomponent vaccine B[symbol: see text]-4 to elderly persons, constituting a risk group with respect to acute respiratory diseases and exacerbations of chronic inflammatory diseases of respiratory organs, was studied. The nasal-oral administration of the vaccine induced immunological shifts in the systems of local and systemic immunity. The content of the populations of lymphocytes with markers CD3, CD4, CD16, CD20 was found to have positive dynamics. Considerable shifts in the system of local immunity were registered: the content of sIgA and IgA in the saliva greatly increased; in addition, an increase in the titers of antibodies to Staphylococcus aureus, Klebsiella pneumoniae and Escherichia coli was observed in persons with initially low titers.