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[An immunomodifier--staphylococcal anatoxin--prevents the development of immunosuppression caused by informational stress in mice].

The action of information stress for 14 days leads to the development of immunosuppression, which is manifested by the suppression of humoral response to sheep red blood cells (SRBC) and the decrease of resistance to Langat virus having low pathogenicity. As shown in this investigation, an immunomodifier, purified staphylococcal toxoid (PST), protects experimental animals from the immunosuppressive effect of information stress. After the injection of PST to stress-affected mice in doses of 15 or 1.5 binding units per animal on days 9, 11 and 13 of the experiment their humoral response to SRBC and resistance to Langat virus are partially restored (by 45-60%).

Adjuvants, Immunologic↗

[The effect of immunomodulating doses of purified staphylococcal anatoxin on the spontaneous and mitogen-induced proliferation of mouse splenocytes].

Purified staphylococcal toxoid (PST) was shown to alter the spontaneous and mitogen-induced proliferation of mouse spleen cells. In vitro, PST inhibited spontaneous proliferation, as well as proliferation induced by the optimal dose of Con A (2 micrograms/ml) and the optimal and suboptimal doses of lipopolysaccharide (LPS) (100 and 50 micrograms/ml). At the same time the dose of 1.5 binding units (BU) of PST, inhibiting spontaneous proliferation in vitro, induced strong proliferative response in combination with the suboptimal dose of Con A (1 microgram/ml). Our experiments demonstrated that the spontaneous proliferation of mouse spleen cells, immunized with the toxoid, remained unchanged (0, 15 or 15 BU/mouse) or increased (1.5 BU/mouse) the response of spleen cells of immune animals to ConA and LPS also changed in comparison with the control, depending on the conditions of the experiment. After the use of the combination of 2 micrograms of Con A and 1.5 BU of PST or 100 (50) micrograms of LPS and 1.5 BU of PST the inhibition of proliferative response was observed. The summation of the signals of the suboptimal dose of Con A (1 microgram) 1.5 BU of PST was demonstrated.

Adjuvants, Immunologic↗

[Immunomodulation activity of new vaccines for pertussis prophylaxis--acellular pertussis vaccine and adsorbed DPT vaccine with acellular component].

The immunomodulating activity of acellular pertussis vaccine (APV) and adsorbed DPT vaccine with acellular pertussis component (DPTA vaccine) was studied. The study revealed that only large doses of APV, 10 immunizing doses (ID), suppressed humoral and cell-mediated response to sheep red blood cells (SRBC). 1 ID produced no influence on the formation of antibody producing cells, but increased the development of delayed hypersensitivity (DH) to SRBC. The modulation of cell-mediated immune response, induced by APV, returned to normal after the injection of purified staphylococcal toxoid, used as immunomodulator, in doses of 0.15 BU per mouse and 1.5 BU per mouse. DPTA vaccine containing 1 ID, as well as 10 ID, produced no immunomodulating effect. This was established by the evaluation of humoral response to SRBC in CBA mice and the study of the formation of DH to SRBC in BALB/c mice. As indicated by the total of the presented data, the inclusion of APV into DPTA vaccine enhanced the immunological safety of its pertussis component.

Adjuvants, Immunologic↗

[Patterns in the antigen-nonspecific modulation of the B-cell activity in mice under the influence of a purified staphylococcal anatoxin].

Purified staphylococcal toxoid (PST) has been shown to be an antigen-nonspecific immunomodulator, capable of inducing changes in the immune response of B-cells to unrelated antigens, such as sheep red blood cells (SRBC), in a wide range of doses (from 15 to 0.15 binding units per mouse). The manifestation of the immunomodulating effect depends on the conditions of the experiment: the doses of PST and SRBC, the age of mice, the sequence of the injections of the antigens and the intervals between the injections. The simultaneous injection of PST and SRBC induces, as a rule, an increase in immune response to the test antigen, while their separate injection induces mainly immunosuppression.

Adjuvants, Immunologic↗

[Immunomodulators of microbial origin enhance cytotoxicity of human mononuclear leukocytes and reduce metastatic progression of Lewis lung carcinoma in mice].

Effect of immunomodulators for microbial origin on innate immunity and antitumor system was continued to study. Immunomodificator Immunovac VP-4, purified staphylococcal toxoid and glucosaminyl muramyl dipeptide (GMDP) equally enhanced cytotoxicity of mononuclear leukocytes of peripheral blood of healthy donors. Index of cytotoxicity was 2.78, 2.77 and 2.70 respectively. Reduced metastatic progression of Lewis lung carcinoma in mice was observed after Immunovac VP-4 and GMDP administration. Effectiveness was seen when preparations administered according to schedules including their administration before implantation of the tumor. If preparations were administered number of metastases reduced in 4.4-5.6 times and size of metastases reduced in 7-10 times. Interplay between antitumor activity of studied immunomodulators and cytotoxic activity of NK-cells, which are base effectors of antitumor immune response, are discussed.

Acetylmuramyl-Alanyl-Isoglutamine↗

[Characteristics of the immune response to staphylococcal anatoxin in healthy persons].

The immunization of young healthy males with adsorbed staphylococcal toxoid revealed the existence of two main types of postimmunization humoral response. One of them was characterized by an early (on days 7-14 after immunization) rise in the titer of antibodies with the subsequent gradual decrease of their content, while the number of circulating T-suppressors remained unchanged. The characteristic feature of the other type was a slow rise in the level of antitoxins by day 21 after immunization with the subsequent drop of their titers, preceded by a considerable increase in the number of circulating T-suppressors. The maximum antibody titer was definitely higher in the first type of response than in the second type (14.8 +/- 1.41 and 9.0 +/- 1.53 I. U./ml respectively). A single plasmapheresis procedure on day 21 after immunization produced no essential effect on the dynamics of the characteristics of cell-mediated and humoral immunity.

Adolescent↗

The adjuvant activity of fatty acid esters. The role of acyl chain length and degree of saturation.

Water-in-oil emulsions of metabolizable fatty acid esters, with the non-toxic surfactant Pluronic L122 as emulsifying agent, potentiated the humoral response to bovine serum albumin and staphylococcal toxoid in the mouse. Adjuvant activity was increased by changing the chemical nature of the esters as follows: (i) using a series of ethyl esters, adjuvant activity appeared when the acyl chain length of the fatty acid component was 16 or greater; (ii) isobutyl and isopropyl esters of palmitic acid (C16:0) were superior to ethyl; (iii) the ethyl esters of oleic (C18:1) and linoleic (C18:2) acids were better than stearic (C18:0). Since emulsions prepared with longer chain saturated esters are very viscous or solid at room temperature, and unsaturated esters are chemically reactive, emulsions were prepared with differing proportions of ethyl caprate (C10:0) and butyl stearate. At a ratio of 9:1 the emulsions possessed the low viscosity of ethyl caprate, but gained the adjuvant activity of butyl stearate. 125I-labelled BSA was retained in the footpad to a significantly greater extent than with a caprate emulsion, but reasons are given for believing that slow release of antigen is not the only mechanism of adjuvant activity. The ester emulsions caused more acute but less chronic local inflammation (footpad swelling) than Freund's incomplete adjuvant.

Adjuvants, Immunologic↗

[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.

Aerosols↗

Biosensor detection of botulinum toxoid A and staphylococcal enterotoxin B in food.

Immunoassays were developed for the simultaneous detection of staphylococcal enterotoxin B and botulinum toxoid A in buffer, with limits of detection of 0.1 ng/ml and 20 ng/ml, respectively. The toxins were also spiked and measured in a variety of food samples, including canned tomatoes, sweet corn, green beans, mushrooms, and tuna.

Animals↗

Vaccination against experimental staphylococcal mastitis in ewes.

Experiments were carried out in ewes using a new vaccine developed for the prevention of mastitis caused by Staphylococcus aureus. The vaccine comprised three major components: (i) killed S aureus cells which had been cultured to induce synthesis of pseudocapsule; (ii) toxoided staphylococcal beta haemolysin and (iii) the adjuvant dextran sulphate. Ewes systemically vaccinated twice during pregnancy developed significantly elevated circulating levels of IgG1 and IgG2 anti-pseudocapsule antibody, as well as increased serum titres of anti-beta haemolysin. Five different strains of S aureus were used to challenge both vaccinated and control ewes by the intramammary route during the ensuing lactation. The incidence of acute gangrenous mastitis and nonacute, clinical mastitis was significantly lower in vaccinated than in control groups after challenge with each strain. Vaccinated ewes produced significantly more milk than control ewes after challenge with four of the five strains of S aureus.

Animals↗

Biodegradable and biocompatible poly(DL-lactide-co-glycolide) microspheres as an adjuvant for staphylococcal enterotoxin B toxoid which enhances the level of toxin-neutralizing antibodies.

Microspheres composed of biocompatible, biodegradable poly(DL-lactide-co-glycolide) (DL-PLG) and staphylococcal enterotoxin B (SEB) toxoid were evaluated as a vaccine delivery system when subcutaneously injected into mice. As measured by circulating immunoglobulin G (IgG) antitoxin titers, the delivery of SEB toxoid via DL-PLG microspheres, 1 to 10 microns in diameter, induced an immune response which was approximately 500 times that seen with nonencapsulated toxoid. The kinetics, magnitude, and duration of the antitoxin response induced with microencapsulated toxoid were similar to those obtained when an equal toxoid dose was administered as an emulsion with complete Freund adjuvant. However, the microspheres did not induce the inflammation and granulomata formation seen with complete Freund adjuvant. The adjuvant activity of the microspheres was not dependent on the superantigenicity of SEB toxin and was equally effective at potentiating circulating IgG antitrinitrophenyl levels in response to microencapsulated trinitrophenyl-keyhole limpet hemocyanin. Empty DL-PLG microspheres were not mitogenic, and SEB toxoid injected as a mixture with empty DL-PLG microspheres was no more effective as an immunogen than toxoid alone. Antigen-containing microspheres 1 to 10 microns in diameter exhibited stronger adjuvant activity than those greater than 10 microns, which correlated with the delivery of the 1- to 10-microns, but not the greater than 10-microns, microspheres into the draining lymph nodes within macrophages. The antibody response induced through immunization with microencapsulated SEB toxoid was protective against the weight loss and splenic V beta 8+ T-cell expansion induced by intravenous toxin administration. These results show that DL-PLG microsphere vaccine delivery systems, which are composed of pharmaceutically acceptable components, possess a strong adjuvant activity for their encapsulated antigens.

Adjuvants, Immunologic↗

Immune modulation with a staphylococcal preparation in fibromyalgia/chronic fatigue syndrome: relation between antibody levels and clinical improvement.

The aims of this study were to evaluate the serological response to treatment with staphylococcal vaccine in fibromyalgia/chronic fatigue syndrome patients and to explore the relationship between serological response and clinical effect. Twenty-eight patients, half of whom served as controls, were recruited from a 6-month randomised trial in which repeated administration of the staphylococcal toxoid vaccine Staphypan Berna (Berna Biotech, Switzerland) was tested against placebo. Antibody status against extracellular toxins/enzymes, cell-wall components, and enterotoxins was evaluated at baseline and at endpoint. The clinical response to treatment was recorded in rating scales. In the group receiving active treatment, significant serological changes were recorded, whereas no significant changes were found in controls. Treatment led to a significantly increased capacity of serum to neutralise alpha-toxin and a significant increase in serum IgG to alpha-toxin and lipase. Furthermore, the increase in these parameters combined paralleled the improvement in clinical outcome. Thus, the greater the serological response, the greater was the clinical effect. In conclusion, this explorative study has shown that repeated administration of the Staphypan Berna vaccine in patients with fibromyalgia/chronic fatigue syndrome causes a serological response to several staphylococcal antigens, particularly to certain extracellular toxins and enzymes. The results further show that this response is related to the clinical outcome of treatment.

Adult↗

ROLE OF ALPHA-TOXIN IN LESION FORMATION BY STAPHYLOCOCCUS AUREUS ON SUTURES SUBCUTANEOUSLY IMPLANTED IN MICE.

Taubler, James H. (University of Pennsylvania, Philadelphia), Frank A. Kapral, and Stuart Mudd. Role of alpha-toxin in lesion formation by Staphylococcus aureus on sutures subcutaneously implanted in mice. J. Bacteriol. 86:51-57. 1963.-Evidence was obtained that alpha-hemolysin is essential for the development of purulent lesions by several strains of Staphylococcus aureus adsorbed onto sutures subcutaneously implanted in mice. This evidence consisted of findings that active immunization with staphylococcal toxoid afforded significant protection to subcutaneous challenge with this organism and that alpha-hemolysin-negative mutants, derived from strains 18Z and P78, were almost devoid of the ability to produce lesions by this route of infection. However, other unknown factors also appear to be essential for lesion formation since passive immunization of mice with antialpha-toxin, obtained from rabbits immunized with purified toxin, failed to afford protection. A dose-response curve for this type of infection is also presented.

Animals↗