[Experimental, clinical and immunologic assessment of acellular staphylococcal vaccine "Staphylovac"].

Results of experimental, clinical and immunological effects of acellular dry staphylococcal vaccine "Staphylovac" developed in Mechnikov Research Institute of Vaccines and Sera are presented. Original mildly virulent strains of Staphylococcus aureus having high immunogenicity, and intra- and interspecies protective activity against different representatives of opportunistic microflora were used for construction of the preparation. Low-toxicity and weak anapylactogenicity of the vaccine were established. In experiments on mice, guinea pigs and rabbits significant protective, antigenic and immunomodulate activity of the preparation was revealed with low sensitization of animals. Clinical trials performed in different centers showed that inclusion of vaccinotherapy in complex treatment of chronic staphylococcal infections (chronic pyodermia, lung abscess etc.) resulted in prolonged pathologic locus, decrease of number and severity of exacerbations, prolongation of remission, and complete recovery in significant number of patients. Activation of innate and adaptive immunity was revealed in the same patients. It was shown on the large group of athletes that administration of the vaccine by aerosol route prevents disruption of immunologic adaptation occurring due to excess physical activity and stress situations during competitions.

[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.

[Immunological characteristics in the therapy of atopic dermatitis in children with polycomponent vaccine Immunovac BN-4].

IgE-mediated reactions linked with the polarization of the immune process towards, mainly, the activation of Th2 lymphocytes which synthesized interleukins, responsible for switching over B lymphocytes to the production of IgE, were found to be the most important mechanism of the pathogenesis of atopic dermatitis (AD). The use of immunomodulating preparations, capable of changing unbalance in the system of Th1/Th2 cells, is one of promising approaches to the complex therapy of AD. Poly-component vaccine Immunovac BN-4 was included into the complex therapy of AD in children, The dynamics of immunological characteristics was studied for the period of 6 months after the end of the course of therapy. A considerable increase in the absolute and relative amount of lymphocytes with markers CD3, CD4, CD16, CD21, CD25, a rise in the levels of IgA, IgG and a decrease in the level of total IgE in the blood serum were established. The inclusion of the polycomponent vaccine into the complex therapy of AD may be recommended.

[Optimization of the therapy of atopic dermatitis by means of immunotherapy].

Taking into account disturbances in the functioning of the immune system in atopic dermatitis (AD) and the potentiating role of staphylococcal and other infections, the possibility of the optimization of the therapy of AD with the use of preparations having immunomodulating action and immunogenic activity is proposed. In the complex therapy of AD in children we used polycomponent vaccine Immunovac B-4, introduced intranasally and orally. Under the influence of immunotherapy the clinical characteristics of the patients had pronounced positive dynamics. A considerable decrease in the spread of the process, the degree of its severity and subjective symptoms was noted shortly after the course of vaccine treatment. Simultaneously the SCORAD index dropped from 64.5 to 39.4. During the later period of observation further decrease in the severity of the course of AD in children occurred, and the minimal characteristics were observed in 6 months of observation. At that time the SCORAD index fell to 19.9 +/- 1.34. The volume of pharmacotherapy and the number of acute respiratory infections considerably decreased, the positive dynamics of the quantitative and qualitative composition of the intestinal microflora was noted. The prolonged immunotherapeutic effect of the polycomponent vaccine made it possible to recommend the vaccine for the optimization of the therapy of AD.

[Immunostimulating activity of polycomponent vaccine "Immunovac-VP-4" and grippol after their combined administration]. / Immunostimuliruiushchaia aktivnost' polikomponentnoi vaktsiny "Immunovak-VP-4" i grippola pri sovmestnom vvedenii.

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.

[Use of the multi-component VP-4 vaccine to prevent acute respiratory diseases at preschool children's establishments]. / Isopol'zovanie polikomponentnoi vaktsiny VP-4 dlia profilaktiki ostrykh respiratornykh zabolevanii v detskikh doshkol'nykh uchrezhdeniiakh.

The multicomponent VP-4 vaccine from Klebsiella pneumonia, Staphyloccocus aureus, Proteus vulgaris, Escherichia coli antigens was used to prevent acute respiratory diseases (ARD) at preschoolchildren's establishments. Prevention was effected during an influenza epidemic with a drastic rise in the incidence of ARD. The VP-4 use involved 3 nasal and 6-9 oral administrations of the drug at an interval of 3-4 days. The duration of the course was 26 +/- 4 days. The preventive action of VP-4 on the incidence of ARD was followed up for 14 months after vaccination. One group comprised 89 vaccinated children, a matched group included 69 children whose age was 2 to 6 years. Immunoprophylaxis was found to promote a reduction in the number of children who had 4 ARD episodes or more during the whole follow-up. Administration of VP-4 prevented the development of repeated episodes ARD in a group of children aged 2-3 years and in frequently ill children who had 3 infections or more in the previous year. The slight reactogenicity of the drug and its long-term preventive effect allow this method of immunoprophylaxis to be recommended for frequently ill children, for those at high risk, and for those in the junior age group (under 4 years) before going to preschoolchildren's establishments.

[Dynamics of autoantibodies in elderly persons in the process of vaccination with Grippol and multicomponent vaccine VP-4]. / Dinamika autoantitel u pozhilykh liudei v protsesse vaktsinatsii grippom i polikomponentnoi vaktsinoi VP-4.

The dynamics of antibodies to organ specific and organ nonspecific antigens in the process of combined immunization with Grippol, an influenza polymer subunit vaccine and polycomponent vaccine VP-4 used for prophylaxis of acute respiratory infections, was under study. Persons aged 65 years and older were vaccinated. Grippol alone was introduced in a single subcutaneous injection into 92 persons and Grippol in combination with vaccine VP-4--to 103 persons. B[symbol: see text]-4 Vaccine was introduced intranasally and orally (6-8 doses). The administration of vaccine VP-4 was started simultaneously with vaccination with Grippol. Prior to immunization and 1 and 5 months later autoantibodies to the following antigens were detected: DNA (native and denaturated), collagen, elastin, myelin basic protein, microsomal fractions of kidneys, lungs, heart, liver, intestine, pituitary body, thyroid gland, pancreas, adrenal glands, ovaries, mucous and muscular layers of stomach. The number of persons with the level of antibodies at least to one of the antigens under study exceeding the normal values prior to vaccination varied from 19.4 +/- 8.6% to 41.5 +/- 7.7%, the average values of positive sera being 0.26 +/- 0.05 to 0.32 +/- 0.08 delta OD. One and 5 months after vaccination both values varied within the same limits in both groups. Immunization with Grippol as well as with its combination with vaccine VP-4 was found to increased spectrum of antibodies to tissue antigens and their increased content. The data give evidence that Grippol and vaccine Vp-4, introduced according to the immunization schedule used in these experiments, do not induce development of autoimmune processes.

[Immunoprophylaxis of acute respiratory diseases with bacterial multicomponent vaccine VP-4 in children at preschool institutions]. / Immunoprofilaktika bakterial'noi polikomponentnoi vaktsinoi (VP-4) u detei v doshkol'nykh uchrezhdeniiakh.

The prophylactic action of polycomponent vaccine B[symbol: see text]-4, prepared from the antigens of opportunistic bacteria, on morbidity rate in acute respiratory diseases (ARD) of bacterial and mixed (bacterial and viral) etiology in 121 children aged 2-5 years, attending pre-school institutions was evaluated. For comparison, a group of 118 children of the same age from the same institutions was formed. The vaccine was introduced after the schedule consisting of 3 intranasal and 6-9 oral administrations made at intervals of 3-4 days. The duration of the course of immunization was 26 +/- 4 days. The prophylactic effect of B[symbol: see text]-4 on ARD morbidity was evaluated by the number of ARD cases and their duration per child. The prophylactic effect of B[symbol: see text]-4 on ARD morbidity lasted 14 months (the term of observation) after immunization and was manifested by a decrease in the number and duration of ARD cases after administration of the preparation, also in a group of highly susceptible children.

[Immune response following administration of multicomponent vaccine VP-4 in elderly patients]. / Immunologicheskie pokazateli pri vvedenii polikomponentnoi vaktsiny VP-4 litsam pozhilogo vozrasta.

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.

[The reactogenicity and safety of a multicomponent vaccine (VP-4) in the prevention of acute respiratory diseases in preschoolers]. / Reaktogennost' i bezopasnost' polikomponentnoi vaktsiny (VP-4) pri profilaktike ostrykh respiratornykh zabolevanii u doshkol'nikov.

The reactogenicity and safety of poly-component vaccine (VP-4), prepared from the antigens of opportunistic bacteria, in the prophylaxis of acute respiratory diseases (ARD) in children aged 2.6-6 years. The vaccine was administered intranasally in 3 administrations and orally in 6-8 administrations at intervals of 3-4 days for a period of 24 +/- 4 days. The prophylaxis of ARD with the use of VP-4 was carried out in 168 children in 4 children's preschool institutions. The control group was made up of 120 children, attending the same institutions. The study revealed that VP-4 had low reactogenicity and induced short-time systemic and local reactions (common cold, cough). The administration of VP-4 at a period of the epidemic rise on influenza and ARD morbidity did not lead to an increase in the frequency and duration of ARD in the vaccinees, as well as to the exacerbation of chronic infection and the allergization of the body.

[Protective efficacy of combined administration of the multicomponent vaccine and the immunomodulator myelopid in experimental infections in mice]. / Protektivnaia éffektivnost' sovmestnogo primeneniia polikomponentnoi vaktsiny i immunomoduliatora mielopida na model'nykh infektsiiakh myshei.

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.

[The immunotherapy of bronchial asthma with a multicomponent vaccine administered intranasally and orally]. / Immunoterapiia bronkhial'noi astmy polikomponentnoi vaktsinoi pri intranazal'no-oral'nom vvedenii.

Multicomponent vaccine prepared from opportunistic bacteria, when administered intranasally and orally to patients with bronchial asthma and chronic bronchitis, was well tolerated by the patients. Side effects induced by the vaccine in a few patients lasted for a short time and were mainly local. Immunotherapy with the vaccine led to a decrease in the severity of the course of the disease, as well as in the frequency and severity of exacerbations. In 26 out of 35 adult patients (74.3%) good and excellent effect was noted; during the observation of 20 sick children aged up to 3 years for a period of 1 year similar effect was noted in 60% of cases. Vaccinal therapy, in addition to its main effect, also contributed to a considerable drop in the morbidity rate of acute respiratory diseases among susceptible children.

[The efficacy and reactogenicity of a cell-free staphylococcal vaccine in the immunotherapy of patients with chronic pyodermas]. / Effektivnost' i reaktogennost' beskletochnoi stafilokokkovoi vaktsiny pri immunoterapii bol'nykh khronicheskimi piodermiiami.

The clinical effectiveness, reactogenicity and immunological activity of cell free staphylococcal vaccine in the immunotherapy of chronic pyoderma patients under the conditions of controlled trials were studied. Immunotherapy was carried out in combination with traditional methods of treatment. A group of 39 patient received cell free staphylococcal vaccine subcutaneously; the second control group (30 patients) received the commercial preparation of staphylococcal antiphagin and the third group (31 patients) was treated by traditional methods without vaccines. The study revealed that cell free staphylococcal vaccine had low reactogenicity and was well tolerated by patients; in contrast to the methods of treatment in the control groups, the vaccine stimulated an increased levels of specific antibodies and IgA in the blood of the patients. Immunotherapy with cell free staphylococcal vaccine led to clinical convalescence and remission in 1-3 years (the term of observation) in 71.8% of cases. In the two control groups such effect did not exceed 23%.

[The immune reactivity of patients with chronic bronchitis on vaccinal therapy]. / Immunoreaktivnost' bol'nykh khronicheskim bronkhitom pri vaktsinoterapii.

The treatment of 17 patients having chronic obstructive bronchitis with a combined vaccine resulted in a rise in the number of T lymphocytes and T suppressors, as well as a simultaneous increase in their functional activity, in these patients. Moreover, an increase in the ingestive activity of neutrophils and in the concentration of immune complexes was registered. Treatment with the vaccine containing Staphylococcus aureus, Klebsiella pneumoniae, Proteus and Escherichia coli antigens facilitated an increase in the titers of antibodies to most antigens contained in the vaccine and in the resistance of the body to infection. Vaccinal therapy made it possible to achieve a significant prolongation of the period of remission.

[The antigenic activity of vaccines made from opportunistic microorganisms in an experiment to immunize animals by oral and combined methods]. / Izuchenie antigennoi aktivnosti vaktsin iz uslovno-patogennykh mikroorganizmov v éksperimente immunizatsii zhivotnykh oral'nymi i kombinirovannymi metodami.

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 reactogenicity and efficacy of a dried cell-free staphylococcal vaccine in treating chronic bronchitis]. / Reaktogennost' i éffektivnost' sukhoi beskletochnoi stafilokokkovoi vaktsiny pri lechenii khronicheskikhh bronkhitov.

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.

[The effect of immunotherapy with cell-free vaccines made from the antigens of opportunistic microorganisms on the dynamics of DNA antibody formation]. / Izuchenie vliianiia immunoterapii beskletochnymi vaktsinami iz antigenov uslovno-patogennykh mikroorganizmov na dinamiku obrazovaniia antitel k DNK.

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.