[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.

[Morphological alterations in animal organs after the injection of acellular pertussis vaccine with immunomodulator]. / Morfologicheskie izmeneniia v organakh zhivotnykh posle vvedeniia beskletochnoi kokliushnoi vaktsiny s immunomoduliatorom.

Toxic properties of acellular pertussis vaccine (APV) and morphological changes in white mice in response to intramuscular injection of APV (without or with immunomodulator glucosaminylmuramyl dipeptide-GMDP) were under study. APV used in these experiments was developed at the Mechnikov Research Institute for Vaccines and Sera (the Russian Acad. Med. Sci.) on the basis of Bordetella pertussis cultures in synthetic fluid culture media. In experiments on acute and chronic toxicity of APV (without GMDP) increased tissue immunity reactions in spleen, thymus, liver, lungs and intestinal wall was detected. There was no difference in immunomorphological reactions in mice receiving APV with different doses of GMDP, but some difference was observed in time dynamics of tissue immunity reactions. A small dose of GMDP should be preferred (0.0001 microgram) which results in gradual growth of tissue immunity reactions less pronounced toxic reactions caused be the APV injection.

[Humoral response to the injection of acellular Pertussis vaccine]. / Gumoral'nyi otvet na vvedenie beskletochnoi kokliushnoi vaktsiny.

The humoral response of mice and rabbits to the injection of whole-cell pertussis vaccine (PV) and acellular pertussis vaccine (APV), developed at the Mechnikov Research Institute for Vaccines and Sera (Russian Acad. Med. Sci.) in Moscow, was studied. In the sera of immunized animals antibodies to the antigenic complex were determined in the direct hemagglutination (DHA) test, specific antibodies to filamentous hemagglutinin (FHA) and pertussis toxin (PT)--in the enzyme immunoassay (EIA) and antibodies neutralizing PT in a cytopathogenic dose (CPD)--in neutralization test on Chinese hamster ovary (CHO) cells. In mice and rabbits immunized with APV the antibody titers determined in the DHA test were higher than those in the animals immunized with PV. Specific antibodies titers to FHA and PT in the sera of rabbits immunized with APV were also higher than those in the sera of rabbits immunized with PV. High dilutions of sera taken from the animals immunized with APC neutralized 4-16 doses of PT in the neutralization test on CHO cells. The most important result of this study was the detection of a more pronounced immune response in the animals immunized with APV in comparison with that induced by PV according to the results obtained in EIA and in the test of PT CPD neutralization on CHO cells.

[A polyvalent complex of Bordetella pertussis antigens as the basis for an acellular pertussis vaccine]. / Polivalentnyi kompleks antigenov Bordetella pertussis kak osnova beskletochnoi kokliushnoi vaktsiny.

The immunogenic and protective properties of acellular pertussis vaccines, prepared on the basis of B. pertussis multicomponent protective complex and the preparation containing only pertussis toxin, were studied. The study revealed that multicomponent preparations containing pertussis toxin (PT), filamentous hemagglutinin, agglutinogens, pertactin and adenylate cyclase possessed more pronounced immunobiological and protective properties in comparison with the monovalent preparation of PT, which was indicative of the expediency of developing acellular pertussis vaccines on the basis of the polyvalent protective complex as minor protective antigens seemed to enhance the protective action of pertussis toxoid, the main protective antigen.

[An acellular pertussis vaccine based on the natural complex of antigens isolated from the supernatant of a synthetic culture medium]. / Beskletochnaia kokliushnaia vaktsina na osnove prirodnogo kompleksa antigenov, vydelennykh iz supernatanta sinteticheskoi sredy kul'tivirovaniia.

A highly effective technology for obtaining a protective antigenic complex, including the main Bordetella pertussis protective antigens (pertussis toxin, filamentous hemagglutinin, agglutinogens, pertactin and adenylate cyclase) and isolated from the supernatant of B. pertussis cultivation medium, has been developed. A new method for the detoxication of antigenic complex which more available to preserve the protective property was suggested. Experimental batches of monovaccine and adsorbed DPT vaccine with the acellular pertussis component, possessing high protective activity and low histamine-sensitizing properties, have been obtained. The stability of protective properties both in liquid and lyophilized acellular pertussis preparations has been noted.

[The expression of Bordetella pertussis protective antigens during bacterial multiplication on a medium with a fixed chemical composition]. / Ekspressiia protektivnykh antigenov Bordetella pertussis v protsesse razmnozheniia bakterii v srede opredelennogo khimicheskogo sostava.

The possibility of obtaining native pertussis preparations with high immunobiological activity has been shown. To obtain such preparations, the use of B. pertussis selected strain, its growth under the conditions of static cultivation in a synthetic culture medium and the use of supernatants with the maximum content of protective antigens with the aim of obtaining protective complexes are necessary.

[A comparative analysis of the antigenic complexes isolated from synthetic and semisynthetic media for the cultivation of Bordetella pertussis]. / Sravnitel'nyi analiz antigennykh kompleksov, vydelennykh iz sinteticheskoi i polusinteticheskoi sred kul'tivirovaniia Bordetella pertussis.

Some physicochemical properties of B.pertussis antigenic complexes isolated from synthetic and semisynthetic culture media have been studied. The chemical composition of these complexes has been determined. Proteins, polypeptide subunits and lipopolysaccharide forming these complexes have been characterized. The presence of two main protective substances of B.pertussis has been revealed: fimbrial hemagglutinin and B.pertussis toxin. The influence of culture medium on the level of the synthesis of B.pertussis adenylate cyclase has been studied.

[The safety and protective properties of a new cell-free pertussis vaccine in animal trials]. / Issledovanie bezvrednosti i protektivnykh svoistv novoi beskletochnoi kokliushnoi vaktsiny v opytakh na zhivotnykh.

The preclinical trial of a new cell-free pertussis vaccine has been carried out with a view to its comparison with whole-cell pertussis vaccine in respect of the toxic and protective properties of the preparations under experimental conditions. The whole-cell pertussis vaccine is characterized by pronounced toxic action causing leukocytosis and histamine-sensitization, produces a negative effect on the detoxifying function of the liver and possesses sensitizing activity. The cell-free pertussis vaccine has pronounced protective activity. In animal experiments the supposed immunization dose of this vaccine has proved to be nontoxic.

[Effect of immunomodulators of various origin on the histamine-sensitizing activity of whole-cell pertussis vaccine]. / Vliianie immunomoduliatorov razlichnogo proiskhozhdeniia na gistaminsensibiliziruiushchuiu aktivnost' korpuskuliarnoi kokliushnoi vaktsiny.

Changes in the histamine-sensitizing activity of whole-cell pertussis vaccine (PV) under the action of immunomodulators (IM) of bacterial (peptide and peptidoglycans), synthetic (peptidoglycan) and vegetable origin have been studied. The study has revealed that these IM, introduced orally and parenterally, exhibit histamine-sensitizing activity, depending on the nature of IM and the optimum selection of the doses of IM and PV.

[The use of monolaurates for removing endotoxins from preparations of cell-free pertussis vaccine]. / Ispol'zovanie monolauratov dlia udaleniia éndotoksinov iz preparatov beskletochnoi kokliushnoi vaktsiny.

The possibility of using monolaurates for removing endotoxin from acellular pertussis vaccines developed at the Laboratory of Immunomodulators, Mechnikov Research Institute for Vaccines and Sera (Moscow), has been studied. Monolaurates PEG-400 and PEG-600 obtained, respectively, from Fluka Chemie AG and Ferak GmbH (Germany) have been used. The use of monolaurate PEG-600 ensures the decrease of the toxicity of acellular pertussis vaccines by 2.34-6.3 times.

[The evaluation of the mutagenic activity of pertussis vaccinal preparations]. / Otsenka mutagennoi aktivnosti kokliushnykh vaktsinal'nykh preparatov.

Two vaccine preparations obtained from Bordetella pertussis, whole-cell vaccine constituting one of the components of adsorbed DPT vaccine and acellular vaccine, were tested for mutagenicity. The doses of the preparations covered the range 1-100 ED50. Ames' test and the metaphase analysis of marrow cells of C57BL/6J mice were used. The acellular preparation was also tested on thymectomized mice, taking into consideration chromosomal aberrations in marrow metaphases. Whole-cell and acellular pertussis vaccines did not induce mutations in Salmonella typhimurium and chromosomal aberrations in mouse marrow cells.

[Isolation of hemolytic cultures of Bordetella pertussis intended for the production of acellular pertussis preparations and the characterization of their biological properties]. / Vydelenie gemoliticheskikh kul'tur Bordetella pertussis dlia prigotovleniia beskletochnykh kokliushnykh preparatov i kharakteristika ikh biologicheskikh svoistv.

The heterogeneity of the population of B. pertussis laboratory strains with respect to the capacity of individual clones to lyse erythrocytes has been established. The complete or partial reduction of the antigens under study in nonhemolytic bacteria has been shown. The use of hemolytic cultures for the preparation of acellular pertussis vaccine makes it possible to increase the content of B. pertussis toxin in these vaccines.

[Physicochemical and biological characteristics of preparations of an antigenic complex isolated from the cultivation medium of Bordetella pertussis]. / Fiziko-khimicheskaia i biologicheskaia kharakteristika preparatov antigennogo kompleksa, vydelennogo iz sredy kul'tivirovaniia kokliushnykh mikrobov.

The physicochemical and biological properties of antigenic complexes isolated from the supernatant fluid of the culture medium of B. pertussis, strains 305 and 475, were studied. The preparations obtained from both strains contained proteins, carbohydrates, nucleic acids and lipids. Electrophoresis in polyacrylamide gel revealed the presence of filamentous hemagglutinin, 4 subunits of B. pertussis toxin and agglutinogens in the antigenic complexes of both strains. The preparations of both strains possessed similar toxic properties and, after their detoxification, produced a pronounced protective effect.

[Characteristics of the biological properties of a cell-free pertussis preparation]. / Kharakteristika biologicheskikh svoistv beskletochnogo kokliushnogo preparata.

The biological properties of Bordetella pertussis antigenic complex, obtained by a technologically simple method from the medium used for the cultivation of B. pertussis, were studied. The preparation was characterized by pronounced hemagglutinating activity, toxicity, histamine-sensitizing and leukocytosis-stimulating activity and produced a cytopathogenic effect on the culture of Chinese hamster ovary cells. The detoxified preparations showed pronounced protective activity in experiments on the active and passive protection of mice. The ED50 of the preparation was 0.146 microgram of protein. In the proposed human immunization dose containing 10 micrograms of protein the detoxified preparation showed no hemagglutinating, leukocytosis-stimulating or histamine-sensitizing activity and proved to be nontoxic in the weight loss test on mice.

[Action of plant extracts on the natural immunity indices of animals]. / Izuchenie deistviia rastitel'nykh ékstraktov na pokazateli estestvennogo immuniteta zhivotnykh.

The influence of extracts from oak bark, St. John's-wort leaves and pine buds on natural immunity characteristics of mice has been studied. The injection of these extracts into mice has been found to enhance their resistance to infection with Staphylococcus aureus and Bordetella pertussis virulent cultures, to decrease the enzymatic activity of 5'-nucleotidase in the peritoneal exudate macrophages of mice and to increase the level of lysozyme in their blood. The action of these extracts has proved to depend on their dosage and the time of observation.

[Effect of blastolysin on the development of specific immunity to whooping cough]. / Vliianie blastolizina na razvitie spetsificheskogo immuniteta k kokliushu.

The influence of blastolysin, the cell-wall glycopeptide of Lactobacillus bulgaricus, on the main immunobiological properties of pertussis vaccine, its immunogenicity and toxicity, has been studied. The use of blastolysin, introduced as a stimulating agent in definite doses and following definite administration schedules, has been shown to permit achieving not only an increase in the immunogenicity of the corpuscular pertussis vaccine, but also a considerable decrease in its toxicity and histamine-sensitizing activity.

[Change in the natural immunity of mice after administration of blastolysin, a glycopeptide from the Lactobacillus bulgaricus cell wall]. / Izmenenie estestvennogo immuniteta myshei pri vvedenii blastolizina--glikopeptida kletochnoi stenki Lactobacillus bulgaricus.

The effect of blastolysin, a glycopeptide of the cell walls of L. bulgaricus, on the resistance of mice to infections caused by S. typhimurium and B. pertussis, lysozyme levels in the blood serum and 5'-nucleotidase activity of peritoneal macrophages was studied. The changes in the nonspecific resistance of mice due to the effect of blastolysin depended on the administration route and the type of the developing infection. It activated the enzymatic activity of the peritoneal macrophages and changed the lysozyme levels in the blood serum of mice. The optimal protective effect of blastolysin was achieved on intramuscular injection in a dose of 100 micrograms.

[Limited controlled trial of the reactogenic properties of ADTP vaccines containing stab cultures as the pertussis component]. / Izuchenie v usloviiakh ogranichennogo kontroliruemogo opyta reaktogennykh svoistv AKDS-vaktsin, soderzhashchikh v kachestve kokliushnogo komponenta glubinnye kul'tury.

The reactogenic properties of adsorbed DPT vaccine containing Bordetella pertussis cultures, grown by submerged cultivation, as the pertussis component were studied. The study revealed that the vaccine was low-reactogenic: no severe postvaccinal reactions were recorded in immunized children. The frequency and intensity of febrile and local reactions in children immunized with adsorbed DPT vaccine under trial and the commercial preparation commonly used in the USSR were identical, but considerably less pronounced than in children immunized with foreign vaccines having similar composition.