The antibody response in the bovine mammary gland is influenced by the adjuvant and the site of subcutaneous vaccination.

Intramammary infections in cattle resulting in mastitis have detrimental effects on cows' well-being, lifespan and milk production. In the host defense against S. aureus mastitis antibodies are thought to play an important role. To explore potential ways to increase antibody titers in the bovine mammary gland the effects of various adjuvants on the magnitude, isotype, and neutralizing capacity of antibodies produced following subcutaneous vaccine administration at different immunization sites were analyzed. In this study, α-toxoid was used as a model antigen and formulated in three different alum-based adjuvants: Alum-Saponin, Alum-Oil, and Alum-Saponin-Oil. Vaccines were administered near the suspensory ligament of the udder or in the lateral triangular area of the neck. At both immunization sites, immunization with α-toxoid in Alum-Saponin-Oil resulted in higher specific antibody titers in milk and serum as compared with Alum-Oil and Alum-Saponin, without favoring an IgG1, IgG2, or IgA response. Furthermore, the neutralizing capacity of milk serum and serum following immunization near the udder and in the neck was higher when Alum-Saponin-Oil was used as adjuvant compared with Alum-Oil and Alum-Saponin. Prime immunizations near the udder effectively increased both antibody isotype titers and neutralization titers, while prime plus boost immunizations were required to induce similar effects following immunization in the neck. Results indicate that subcutaneous administration of an Alum-Saponin-Oil based vaccine near the udder could be further explored for the development of a one-shot vaccination strategy to efficiently increase intramammary antibody responses.

[Adverse immunologic effects of immunomodulators revealed in experiment and ways to their surmounting].

Immunomodulators licopid (synthetic analogue of muramylpeptide) and purified staphylococcal toxoid (PST) in some variants of experiments on mice caused adverse immunologic effects: enhancement of virus-induced immunosupression, shift from latent immunosupression (revealed only by low, but not standard, doses of test-antigen) to manifested one. Described adverse effects are not a contraindication for use of the studied drugs in practice. Their adverse effects were revealed only after single inoculation, whereas in clinical conditions PST and licopid are used by courses with duration of 5-7 and 10 days respectively. Our experiments show that inoculation of suppressive doses of the preparations repeated by 2-4 times can prevent the shift from latent to manifested immunosupression. Enhancement of immunosupression was not observed in case of combined administration of suppressive doses of PST and adjuvant dose of licopid.

[Modulation of antigen-presenting functions in peritoneal macrophages and changes in production of several cytokines in mice caused by purified staphylococcal toxoid].

With adaptive transfer method it has been shown that immunomodulator purified staphylococcal toxoid (PST) changed (stimulate or suppress) antigen-presenting function (APF) of mice peritoneal macrophages (MF) in vivo. This phenomenon was registered during assessment of ability of peritoneal MF to present heterologous (with regard to PST) antigen--sheep erythrocytes (SE). Modulation vector depended from time interval between PST and SE inoculations. Inoculation of PST 1.5 h before SE resulted in stimulation of APF. When SE were inoculated to donor mice 24 h after PST, suppression of APF was developed. Suppression of APF was observed along with suppression of proinflammatory cytokines (IL-1beta, IL-6, TNF-alpha) as well as B-lymphocytes growth factor (IL-4). When cytokine profile was assessed 4 h after PST injection, the suppression of synthesis of these cytokines was not observed. Production of IL-12 increased in 9-12 times in 4 and 24 h after PST injection.

[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.

[The mechanisms of the impact of preliminary immunization with staphylococcus anatoxin on postresuscitation pathology of the myocardium].

Chronic experiments lasting for 5 weeks were carried out in 40 nonpedigree mature dogs. It has been detected that preliminary immunization with staphylococcus anatoxin potentiates the compensation mechanisms in the course of postresuscitation period, stimulates cell proliferation by increasing cardiac output that is an adaptive reaction of the cardiovascular system in postresuscitation period and provides optimal metabolism of the organism.

[Experimental study of the protective activity of a complex staphylococcal antigen and toxoid when administered in combination]. / Eksperimental'noe izuchenie protektivnoi aktivnosti kompleksnogo antigena stafilokokka i anatoksina pri sovmestnom vvedenii.

The data obtained in the experimental study of the protective activity of an antigenic staphylococcal complex prepared by the method of aqueous extraction and staphylococcal toxoid (native and adsorbed) are presented. The study carried out on the model of septic staphylococcal infection in rabbits indicated that after immunization with the mixture of the above-mentioned preparations the survival time of the rabbits increased to a greater extent than after immunization with each of these preparations separately. This regularity was especially pronounced under the aggravated conditions of infection with the mixture of strains.

[Antistaphylococcal bacteriostatic activity of the sera from surgical patients]. / Ob antistafilokokkovoi bakteriostaticheskoi aktivnosti syvorotok khirurgicheskikh bol'nykh

Blood serum was examined in 41 patients (operated for various forms of acute appendicitis) on the 5th--6th day after the operation when 10 of the patients developed purulent complications of staphylococcal etiology. A determination was made of the titres of beta-lysins and the bacteriostatic activity against 2 strains of S. aureus by the modified Ehrenkranz et al method. The mentioned indices were low in the great majority of cases; consequently, the appearance of purulent complications in the operated patients was independent of the antistaphylococcal bacteriostatic activity and the beta-lysin titres in their sera. Prophylactic express-immunization of a number of patients by crude staphylococcus toxoid did not influence the nonspecific humoral immunity factors.

[Efficacy of the per os immunization and reimmunization of man with staphylococcal anatoxin]. / Effektivnost' immunizatsii i reimmunizatsii liudei per os stafilokokkovym anatoksinom.

By double immunization of 72 persons and single reimmunization of 38 persons per os with tablets containing 100 BU of purified concentrated staphylococcus toxoid (PCST) it was revealed that this immunization was harmless and the immunological response was adequate. The tablets were intended for application through the oral mucosa (oral) or the intestinal tract (enteral); the immunological response depended on the dose of the preparation and the scheme of administration. A high sensitization of healthy persons examined to staphylococcus was found. There was a tendency to reduction of hypersensitivity after the immunization with staphylococcus toxoid (examination in 6 months) and activation of reactions after the antigen administration (examination in 14 days).

[Experimental study of the possibility of passage of staphylococcal toxoid from mother to fetus]. / Eksperimental'noe izuchenie vozmozhnosti perekhoda stafilokokkovogo anatoksina ot materi k plodu.

After the immunization of pregnant rats with purified adsorbed staphylococcal toxoid the antigen could be detected 2-48 hours later in the parenchymatous organs (the liver, the spleen), but not in the blood serum and the amniotic fluid. The rats immunized at an early period of pregnancy showed the presence of the antigen in their placenta and fetuses, while after the immunization at a late period of pregnancy the antigen could be only seldom detected in the placenta and practically never in the fetuses. There are grounds to believe that staphylococcal toxoid does not pass from the mother to the fetus through the completely formed placenta.

[Principles of hospital infection control]. / Printsipy bor'by s vnutribol'nichnymi infektsiiami.

The demographic, socio-hygienic, immunological, genetic, microbiological and epidemiological aspects of the problem of hospital purulent inflammatory diseases (PID) are considered. The main causes contributing to the high level of PID are analyzed. The main ways for decreasing PID incidence in medical institutions, comprising a complex of organizational, prophylactic and therapeutic measures introduced by stages, are outlined.

[Changes in the anti-infection immunity indices of esophageal cancer patients undergoing combined immunization against staphylococcal and Pseudomonas aeruginosa infections]. / Izmenenie pokazatelei antiinfektsionnogo immuniteta u bol'nykh rakom pishchevoda pri kompleksnoi immunizatsii protiv stafilokokkovoi i sinegnoinoi infektsii.

The method of the complex immunization of patients with esophageal cancer against the main causative agents of purulent infections has been developed. Purified concentrated staphylococcal toxoid and polyvalent corpuscular P. aeruginosa vaccine were used for the immunization of 26 patients. Immunization was carried out in 3 injections (11 patients) and 4 injections (15 patients) made at intervals of 7 days. This resulted in the activation of nonspecific immunity factors (the total bactericidal properties of the blood serum, the phagocytic activity of neutrophils, the increase of the IgG level) and in a considerable increase in the factors of specific protection against staphylococcal and P. aeruginosa infections: the titer of staphylococcal anti-alpha-toxin increased 7- to 11-fold and the titer of antibodies to P. aeruginosa antibodies increased 5- to 6.5-fold. The preoperative vaccination of patients decreased the occurrence of postoperative purulent complications from 71% to 11.5%.

[Immunoprevention of staphylococcal infections at an industrial enterprise]. / Immunoprofilaktika stafilokokkovykh infektsii na promyshlennom predpriiatii.

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.

[Characteristics of the immune response to staphylococcal anatoxin in healthy persons]. / Osobennosti immunnogo otveta k stafilokokkovomu anatoksinu u zdorovykh lits.

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.

[Correction of immune response using purified staphylococcal toxoid and likopid in the secondary immunodeficiency induced by Coxsackie virus B3]. / Korrektsiia immunogo otveta s pomoshch'iu anatoksina stafilokokkovogo ochishchennogo i likopida pri vtorichnom immunodefitsite, indutsirovannom virusom Koksaki B3.

The action of immunomodulators, purified staphylococcal toxoid (PST) and lycopid, on secondary immunodeficiency state developing during infection caused by Coxsackie virus B3 was studied. This defect was manifested by delayed hypersensitivity to sheep red blood cells (SRBC) and the suppression of neutralizing antibodies to poliomyelitis virus. Depending on the scheme of the experiment, PST normalized the defects of immune response to SRBC or poliovirus, increased suppression or showed no activity. Lycopid corrected the defects of humoral response to SRBC. The combination of PST and lycopid was found to produce no increase of suppression. The suggestion was made on the expediency of combination of two (and probably more) immunomodulators for increasing the efficiency of correction of secondary immunodeficiency.

[The creation of specific immunity to staphylococcal infection in newborn infants by the intranasal administration of adsorbed staphylococcal anatoxin]. / Sozdanie spetsificheskogo immuniteta k stafilokokkovoi infektsii u novorozhdennykh detei putem intranazal'nogo vvedeniia adsorbirovannogo stafilokokkovogo anatoksina.

The possibility of enhancing specific immunity in newborn infants by the intranasal administration of adsorbed staphylococcal toxoid to infants with a high risk of staphylococcal infection in doses of 1 drop (0.05 ml) into each nostril during the first 7-9 years of their life. On days 7-9 the level of anti-alpha-toxin in the blood rose to 3.8 +/- 0.14 I. U./ml and remained sufficiently high 3-6 months later. When this method was used for the simultaneous immunization of mothers, their antitoxic titers were not as high as in newborn infants. No side effects were observed. In the control group, the titers of anti-alpha-toxin were low during the whole period of observation. Infants immunized by the proposed method had no staphylococcal infections both during the newborn period and within the first year of their life. In the control group, 8 cases of minor forms of purulent septic infection were registered during the newborn period, and in 2 infants umbilical staphylococcal sepsis was diagnosed.

[Effect of immunization of pregnant women with staphylococcal toxoid on the immunologic status of the child]. / Vliianie immunizatsii stafilokokkovym anatoksinom beremennoi zhenshchiny na immunologicheskii status rebenka

A study was made of the effect of immunization of women during pregnancy of the immunological status of puerperants and their neonates, and also on the course of pregnancy in women and on development of a child aged under one year. Elevation of the IgG level in the blood serum, of the IgA -- in the milk of puerperants, and of the IgM -- in the blood serum of neonates, and also a marked increase in the antistaphylolysin titre in the mother and the neonate was revealed as a result of immunization. Clinical obervations showed such immunization to be harmless for the women, the neonate and the child the first year after birth. Immunization had a favourable effect on the state health of the children the first year after birth; this was expressed in a greater, in comparison with other children, resistance against infections diseases.

[Study of the functional activity of the macrophages of animals immunized with staphylococcal alpha-anatoxin]. / Izuchenie funktsional'noi aktivnosti makrofagov zhivotnykh, immunizirovannykh stafilokokkovym al'fa-anatoksinom

A study was made by histochemical methods of the activity of the enzymatic systems of macrophages from normal rabbits and those immunized with staphylococcus alpha-toxoid per se and infected with the strains of staphylococcus--producers of alpha-toxin or leukocydin. Immunization of rabbits was accompanied by a reduction in macrophages of the activity of the group of lysosomal enzymes and by an increase in the activity of the redox enzymes. In infection of "immune" macrophages with the living culture of the alpha-toxigenic strains the mentioned changes were more pronounced; no such changes were found after the infection with the leukocydin-active strain. The data obtained suggested that the lysosomal enzymes played a definite role in the process of phagocytosis.

[Protease as an immune response enhancer in immunization with an adsorbed staphylococcal anatoxin]. / Proteaza kak usilitel' immunogo otveta pri immunizatsii adsorbirovannym stafilokokkovym anatoksinom.

The injection of trypsin into rabbits immunized with adsorbed staphylococcal toxoid was found to have a potentiating effect on the immune response of the body, which was manifested by a considerable increase in the specific antibody titer and by the activation of nonspecific systemic protective factors. The intensity of antistaphylococcal immunity achieved by the moment of challenge (on day 23 of the experiment) in the animals ensured the resistance of the rabbits to staphylococcal test infection. The injection of trielin, a proteolysis inhibiting agent, simultaneously with the immunization of rabbits with adsorbed staphylococcal toxoid produced no such effect.

[The characteristics of the protective and antigenic activities of purified staphylococcal anatoxin in trials with mice of different genotypes]. / Kharakteristika protektivnoi i antigennoi aktivnosti anatoksina stafilokokkovogo ochishchennogo v opytakh na myshakh raznykh genotipov.

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.).

[Immunomodulation activity of new vaccines for pertussis prophylaxis--acellular pertussis vaccine and adsorbed DPT vaccine with acellular component]. / Otsenka immunomoduliruiushchei aktivnosti novykh preparatov dlia profilaktiki kokliusha--beskletochnoi kokliushnoi vaktsiny i AKDS-vaktsiny s beskletochnym kokliushnym komponentom.

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.