[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.

[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.

[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.

[Enhancing the effectiveness of microbiological nutrient media through balancing their content by an experimental analytical method]. / Povyshenie éffektivnosti mikrobiologicheskikh pitatel'nykh sred putem balansirovanii ikh sostava s pomoshch'iu éksperimental'no-analiticheskogo metoda.

The possibility of successful use of the analitico-experimental method for the development and improvement of balanced microbiological growth media, economical in composition, has been shown. By this method a new variant of the semisynthetic medium for growing Bordetella pertussis vaccine strain has been obtained, thus making it possible to achieve a considerable increase in the yield of the biomass without decreasing the immunogenicity of the culture. The use of the balanced medium in the production of vaccines may alone give the overall economic effect totalling 11000 roubles per 10000 liters.

[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.

[Cultivation of Bordetella pertussis in liquid semisynthetic nutrient media with ion-exchange resins]. / Kul'tivirovanie kokliushnykh bakterii v zhidkikh polusinteticheskikh pitatel'nykh sredakh s ionoobmennymi smolami.

The possibility of optimizing the processes of B. pertussis cultivation carried out in liquid semisynthetic culture media with strong-base anion-exchange resins is shown. The use of strong-base ionites enhances the reproducibility of cultivation processes, increases the activity of microbial populations and the concentration of microorganisms. B. pertussis cultures grown in the media with anion-exchange resins are characterized by pronounced biological activity.