[Preclinical studies of an adsorbed diphtheria-tetanus-pertussis vaccine (ADTP-vaccine) with acellular pertussis component].

AIM: Evaluate standardness of antigenic composition of pertussis component, completeness of sorption of pertussis, diphtheria and tetanus components, specific activity and safety of experimental series ofADTP-vaccine with acellular pertussis component (ADTaP-vaccine). MATERIALS AND METHODS: The content of separate antigens (pertussis toxin, filamentous hemagglutinin and agglutinogens 1, 2, 3) in samples of acellular pertussis component of ADTaP-vaccine and completeness of sorption of pertussis component of ADTaP-vaccine were evaluated by using enzyme immunoassay. Completeness of sorption of diphtheria and tetanus components were determined in flocculation reaction and antitoxin-binding reactions, respectively. Protective activity ofADTaP-vaccine was studied in model ofmeningoencephalitis development in mice infected with Bordetella pertussis (strain 18323) neurotropic virulent culture, protective activity oftetanus component - by survival of mice after administration of tetanus toxin, protective activity of diphtheria component - by survival of guinea pigs after administration of diphtheria toxin. Safety of preparations was evaluated in tests of acute and chronic toxicity with carrying out pathomorphologic studies including immature animals. RESULTS: All the studied experimental series ofADTaP-vaccine were standard by content of separate antigens of pertussis microbe. All the ADTaP-vaccine components were completely sorbed on aluminium hydroxide gel. By protective activity ADTaP preparations satisfied the WHO requirements. The preparations were non-toxic in acute and chronic toxicity and did not induce pathomorphologic changes including immature animals. CONCLUSION: Experimental samples of ADTaP-vaccine by specific activity and safety satisfied WHO requirements.

[Protective activity of adsorbed D(a)PT vaccine with the acellular pertussis component and polyoxydonium].

The introduction of the immunomodulator polyoxidonium in an amount of 0.5 Mg/ml into adsorbed D(a)PT vaccine with the acellular pertussis component leads to the preservation of the protective activity of the pertusis component, diphtheria and tetanus toxoids, as well to the 4-time decrease of the content of adsorbent (aluminium hydroxide) from 2 to 0.5 mg/ml.

[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.

[The action of pertussis vaccines and GMDP on the change in the enzymatic activity of macrophages from peritoneal exudate]. / Izuchenie deistviia kokliushnykh vaktsin i GMDP na izmenenie fermentativnoi aktivnosti makrofagov peritoneal'nogo ékssudata.

The influence of whole-cell and acellular pertussis vaccines, introduced both alone and in combination with N-acetylglucosaminylmuramyl-2-alanine-D-isoglutamine (GMDP) on the activity of two enzymes of peritoneal exudate macrophages (5'-nucleotidase and Na+K(+)-adenosine triphosphatase) was studied. The study revealed that both pertussis vaccines exhibited immunomodulating properties, these properties being most pronounced in whole-cell pertussis vaccine. The use of GMDP in combination with pertussis vaccines led to changes in the enzymatic activity of peritoneal exudate macrophages, which was indicative of a decrease in the immunomodulating action of pertussis preparations.

[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.

[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.

[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.

[An increase in the immunogenicity of bacterial antigens under the influence of one of the derivatives of muramyl dipeptide]. / Povyshenie immunogennosti bakterial'nykh antigenov pod vliianiem odnogo iz derivatov muramildipeptida.

As revealed in animal experiments, glucosaminylmuramyl dipeptide (GMDP), the synthetic analog of muramyl dipeptide, when introduced intraperitoneally in a single injection or orally, exhibits adjuvant activity with respect to Citrobacter 0-antigens, Shigella flexneri and enhances the protective properties of dysentery and pertussis vaccines. The stimulating properties of GMDP depend on its dose, the route of its administration, the time elapsed after its administration, its ratio to the concomitant doses of bacterial antigens and to the dose of the virulent culture used for challenge.

[A comparative study of the immunological properties of peptidoglycans of different origins]. / Sravnitel'noe izuchenie immunologicheskikh svoistv peptidoglikanov razlichnogo proiskhozhdeniia.

The action of peptidoglycans (PG) of different origin has been experimentally studied in vivo. In these experiments PG of bacterial origin, such as blastolysin (BL), and synthetic PG, viz. muramyldipeptide (MDP) and its analog glucosaminylmuramyldipeptide (GMDP) have been used. Their toxicity, allergenic action, their effect on the phagocytic activity of peritoneal exudate macrophages (PEM), the accumulation of antibody-producing cells in the spleen, antibody titer in the blood serum and delayed hypersensitivity to nonbacterial antigens have been determined. As revealed in this study, BL does not differ from MDP in its toxicity and allergenic action. The phagocytic activity of PEM under the influence of BL only insignificantly differs from their activity under the influence of MDP, but is lower than under the influence of GMDP. The adjuvant action of BL is somewhat higher than that of synthetic PG.

[Metabolic changes in the peritoneal macrophages of mice differing in the H-2 locus of histocompatibility after intraperitoneal administration of salmozan]. / Izuchenie metabolicheskikh izmenenii v peritoneal'nykh makrofagakh myshei, razlichaiushchikhsia po H-2-lokusu gistosovmestimosti, pri vnutribriushinnom vvedenii sal'mozana.

The activity of 5'-nucleotidase in mouse peritoneal macrophages differing by histocompatibility locus H-2 after intraperitoneal injection of salmozan, an immunostimulating agent, has been studied. The character of changes in the activity of 5'-nucleotidase in peritoneal exudate macrophages after the intraperitoneal injection of salmozan has proved to be unrelated to the genotype of mice. The injection of salmozan induces a deep and prolonged decrease in the activity of 5'-nucleotidase in these macrophages. In mice of different strains changes in the activity of 5'-nucleotidase after the intraperitoneal injection of salmozan are of a linear type and can be approximated by a linear regression model.