RESUMEN
Continued circulation of the whooping cough pathogen, even in countries with high vaccine coverage, can be related to persistence of Bordetella pertussis biofilms in the respiratory tract. The films differ from planktonic cells by increased resistance to the host immune system and antibacterial drugs. The available acellular pertussis vaccines (aPV) containing antigens isolated from planktonic cultures of B. pertussis protect from severe forms of whooping cough, but do not effectively influence circulation of virulent strains in the subclinical forms of the disease and asymptomatic carriage. It is promising to create new generation aPV based on antigens isolated from biofilm cultures of B. pertussis capable of more effectively controlling the entire infectious cycle of whooping cough, including colonization, persistence, and transmission of the pathogen. From antigenic complexes isolated from the culture medium of biofilm and planktonic cultures of the strain B. pertussis No. 317 (serotype 1.2.3), experimental aPV were made: aPV-B and aPV-P, respectively. In intracerebral infection of mice with a virulent strain of B. pertussis, aPV-B demonstrated 2.5-fold higher protective activity than aPV-P and also more effectively reduced colonization of the lungs by B. pertussis cells in mice after intranasal infection with a virulent strain. Both vaccine preparations were safe and did not cause death in mice after administration of histamine.
Asunto(s)
Biopelículas , Bordetella pertussis , Vacuna contra la Tos Ferina , Vacunas Acelulares , Tos Ferina , Bordetella pertussis/inmunología , Bordetella pertussis/patogenicidad , Vacuna contra la Tos Ferina/inmunología , Animales , Biopelículas/efectos de los fármacos , Biopelículas/crecimiento & desarrollo , Tos Ferina/prevención & control , Tos Ferina/microbiología , Tos Ferina/inmunología , Ratones , Vacunas Acelulares/inmunología , Plancton/efectos de los fármacos , Plancton/inmunología , Antígenos Bacterianos/inmunología , Femenino , Ratones Endogámicos BALB C , Administración IntranasalRESUMEN
AIM: Study cytokine status in mice immunized with vaccines containing acellular pertussis component. MATERIALS AND METHODS: Vaccines developed in Mechnikov RIVS - acellular pertussis vaccine (aPV) and adsorbed pertussis-diphtheria-tetanus vaccine (aDTaP), containing a complex of protective antigens of pertussis microbe - were used in the study. F1 (CBAxC57B16) line mice weighing 12 - 14 g were immunized intraperitoneally 3 times at an interval of 7 days with aPV and aDTaP at human immunization dose (0.5 ml), containing 25 µg of pertussis component. Intact mice were used as a control group. Levels of IFN-,γ, IL-2, IL-4, IL-5, IL-12 cytokines were de- termined after each immunization in enzyme immunoassay using commercial test-systems from Cusabio (China). RESULTS: An increase of levels of IFN-γ, IL-2, IL-5, IL-12 and lack of stimulation of production of IL-4 was established in dynamics of immune response after administration of aPV and aDTaP vaccines. CONCLUSION: The data obtained indicate that immunization of mice with aPV and aDTaP vaccines resulted in activation of production of cytokines characteristic for im- mune response during pertussis infection and immunization with whole-cellular aDTP-vaccines.
Asunto(s)
Citocinas/inmunología , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/inmunología , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/farmacología , Inmunización , Animales , RatonesRESUMEN
AIM: Study specific activity and safety ofvaccine preparations based on circulating B. pertussis strains with currently predominating allele variants of pertussis toxin (ptxA1) and pertactin (prn2) genes. MATERIALS AND METHODS: B. pertussis strains isolated from pertussis patients in Moscow in 2001-2010 were grown in dense and liquid media. The content of separate antigens in B. pertussis strains was determined by EIA. Immunogenicity and safety of the preparations was determined in F1(CBAxC57B16) line mice. RESULTS: All the studied circulating B. pertussis strains expressed pertussis toxin (PT), filamentous hemagglutinin (FHA) and agglutinogens corresponding to the serovar. Whole-cell and acellular pertussis vaccines were prepared based on the circulating strains, and a highly productive recently isolated toxigenic B.pertussis strain that could be used for production ofpertussis vaccines was selected as a result of studies ofimmunogenic, toxic and sensibilizing properties. CONCLUSION: Vaccine preparations based on a B. pertussis strain adapted to growth in liquid media with pertussis toxin and pertactin ptxAl1 - prn2 gene allele variation characteristic for contemporary population are specifically active and safe.
Asunto(s)
Bordetella pertussis/efectos de los fármacos , Vacuna contra la Tos Ferina/inmunología , Tos Ferina/prevención & control , Alelos , Animales , Bordetella pertussis/inmunología , Bordetella pertussis/patogenicidad , Humanos , Ratones , Moscú , Toxina del Pertussis/inmunología , Tos Ferina/inmunología , Tos Ferina/microbiologíaRESUMEN
AIM: Study of Bordetella pertussis lipopolysaccharide (LPS) immunobiological properties in the acellular pertussis vaccine. MATERIALS AND METHODS: Experimental series of acellular pertussis vaccines (APV), lyophilized LPS were used. Antibody titers against LPS in mice sera were evaluated by using EIA with peroxidase conjugate of anti-species antibodies against mice IgG. LPS activity in B. pertussis antigen complex preparations was determined in quantitative chromogenic LAL-test by end point. APV protective activity was determined in mice test during intracerebral infection by B. pertussis strain No. 18323 virulent culture. APV safety was determined in the mice body weight change test. RESULTS: The presence of LPS in APV was shown in immune electrophoresis with purified B. pertussis LPS preparation as a control. Formalin treatment changes immunochemical properties of APV LPS that lead to the shift of precipitation bands with pertussis agglutinating sera from the start zone into cathode. The quantity of LPS in pertussis culture supernatants was on average 49050 +/- 6774 endotoxin units per ml (EU/ml). In APV preparations the quantity of LPS was on average 906 +/- 90 EU/ml, i.e. decreased by more than 50 times. An increase of antibody titers against B. pertussis LPS in mice sera after the APV immunization was shown in EIA, which gives evidence of its presence in immunogenic form in the complex preparations. The preclinical studies carried out show protective activity and specific safety of the experimental APV series. CONCLUSION: Formalin-neutralized APV preparation is a complex of protein antigens in association with LPS. Formalin treatment results in modification of LPS molecule that retains antigenic properties but is significantly less toxic.
Asunto(s)
Antígenos Bacterianos/inmunología , Bordetella pertussis/inmunología , Lipopolisacáridos/inmunología , Vacuna contra la Tos Ferina/inmunología , Animales , Antígenos Bacterianos/química , Antígenos Bacterianos/farmacología , Bordetella pertussis/química , Humanos , Lipopolisacáridos/química , Lipopolisacáridos/farmacología , Ratones , Vacuna contra la Tos Ferina/química , Vacuna contra la Tos Ferina/farmacología , Vacunas Acelulares/química , Vacunas Acelulares/inmunología , Vacunas Acelulares/farmacología , Factores de Virulencia de Bordetella/química , Factores de Virulencia de Bordetella/inmunología , Factores de Virulencia de Bordetella/farmacología , Tos Ferina/inmunología , Tos Ferina/prevención & controlRESUMEN
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.
Asunto(s)
Adyuvantes Inmunológicos/efectos adversos , Hidróxido de Aluminio/farmacología , Antígenos Bacterianos/farmacología , Bordetella pertussis , Toxina Diftérica/toxicidad , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/farmacología , Meningoencefalitis/prevención & control , Toxina Tetánica/toxicidad , Adyuvantes Inmunológicos/farmacología , Hidróxido de Aluminio/efectos adversos , Animales , Antígenos Bacterianos/efectos adversos , Antígenos Bacterianos/inmunología , Toxina Diftérica/inmunología , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/efectos adversos , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/inmunología , Evaluación Preclínica de Medicamentos , Femenino , Cobayas , Humanos , Masculino , Meningoencefalitis/inmunología , Ratones , Toxina Tetánica/inmunologíaRESUMEN
There are presented the results of genotoxicologic, immunologic and allergologic examinations which were conducted within the framework of integrated medical and biological assessment of genetically modified second generation soybean event MON 89788. Analysis of damages of DNA and structural chromosome aberrations, assessment of the allergenic potential and immunoreactive properties has not confirmed any genotoxic, allergenic and immunotoxic effect of soybean event MON 89788.
Asunto(s)
Análisis de los Alimentos , Alimentos Modificados Genéticamente , Glycine max , Plantas Modificadas Genéticamente , Animales , Cromosomas de los Mamíferos/genética , Cromosomas de los Mamíferos/inmunología , Daño del ADN/genética , Daño del ADN/inmunología , Hipersensibilidad/genética , Hipersensibilidad/inmunología , Masculino , Ratones , Ratas , Ratas WistarRESUMEN
There are presented the results of genotoxicologic, immunologic and allergologic examinations which were conducted within the framework of integrated medical and biological assessment of genetically modified rootworm Diabrotica spp.-protected maize event MIR604. Analysis of damages of DNA and structural chromosome aberrations, assessment of the allergenic potential and immunoreactive properties has not confirmed any genotoxic, allergenic and immunotoxic effect of maize event MIR604.
Asunto(s)
Aberraciones Cromosómicas , Daño del ADN , Análisis de los Alimentos/métodos , Hipersensibilidad a los Alimentos/etiología , Alimentos Modificados Genéticamente/toxicidad , Plantas Modificadas Genéticamente/toxicidad , Zea mays/genética , Zea mays/toxicidad , Anafilaxia/etiología , Anafilaxia/inmunología , Animales , Células de la Médula Ósea/metabolismo , Células de la Médula Ósea/ultraestructura , Colon/metabolismo , Ensayo Cometa , Alimentos Modificados Genéticamente/efectos adversos , Alimentos Modificados Genéticamente/normas , Hipersensibilidad Tardía/etiología , Hipersensibilidad Tardía/inmunología , Hígado/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos CBA , Ovalbúmina , Plantas Modificadas Genéticamente/efectos adversos , Ratas , Ratas Wistar , Especificidad de la Especie , Pruebas de Toxicidad , Zea mays/efectos adversos , Zea mays/normasRESUMEN
AIM: To assess antigenic composition consistency and serological characteristics of domestic acellular pertussis vaccine. MATERIALS AND METHODS: Amount of pertussis toxin, filamentous hemagglutinin, agglutinogens types 1, 2, and 3 in experimental batches of vaccine was measured by enzyme immunoassay. Levels of antibodies to aforementioned antigens as well as to lipopolysaccbaride in serum samples obtained from patients with pertussis and healthy vaccinated children were measured by the same method. The amount of lypopolysaccharide was determined by LAL test. RESULTS: Studied batches of vaccine were standard on amount of all protein antigens as well as lipopolysaccharide. Spectrum of antibodies to vaccine components in serum samples from patients with pertussis and healthy vaccinated children included antibodies to individual antigens: pertussis toxin, filamentous hemagglutinin, lipopolysaccharide, agglutinogens types 1, 2, and 3. CONCLUSION: Developed technology for manufacturing acellular pertussis vaccine allows to consistently produce preparations with standard amount of all components. Vaccine components interact with antibodies to wide spectrum of B. pertussis antigens.
Asunto(s)
Antígenos Bacterianos/inmunología , Bordetella pertussis/inmunología , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/inmunología , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/normas , Tos Ferina/prevención & control , Adolescente , Anticuerpos Antibacterianos/sangre , Antígenos Bacterianos/análisis , Niño , Preescolar , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/administración & dosificación , Humanos , Lactante , Tos Ferina/sangre , Tos Ferina/inmunologíaRESUMEN
AIM: To study pathogenic characteristics of B. pertussis strains isolated from patients during different periods of pertussis infection epidemic process. MATERIALS AND METHODS: Strains of B. pertussis isolated in Moscow during 1967 - 1971, 1980 - 1985, and 2001 - 2005 were studied. Nutrient media: Bordet-Gengou blood agar, casein-charcoal agar. ANIMALS: mice - F1 hybrids (CBA x C57BL6). Pathogenic characteristics of strains were studied by assessment of virulence (LD50), leukocytosis-stimulating (LS units) and histamine-sensitizing (HSD50) activities of cultures. Genotyping was performed using standard equipment and reagents for DNA isolation, amplification, sequencing and detection of results. RESULTS: On the sample of 164 strains, pathogenic and genotypic characteristics of B. pertussis populations circulated during 1967 - 1971, 1980 - 1985, and 2001 - 2005. Majority of B. pertussis strains isolated in 1967 - 1971 and strains circulated during current phase of epidemic process were virulent (80.75% and 81.8% respectively) and had significant leukocytosis-stimulating and histamine-sensitizing activity, whereas strains isolated from patients with pertussis in 1980 - 1985 characterized by lower virulence and toxicity. Genotyping showed strains carrying "non-vaccine" allele ptxA1, which emerged in the middle of 1970s, totally displaced strains with "vaccine" alleles ptxA2 and ptxA4. CONCLUSION: Adaptive changes of B. pertussis driven by increased vaccination coverage involve both ptxA gene and pathogenic characteristics of infectious agent in the range of genotypically homogenous population with domination of strains, which have high levels of virulence and toxicity.
Asunto(s)
Bordetella pertussis/patogenicidad , Tos Ferina/microbiología , Animales , Bordetella pertussis/genética , Bordetella pertussis/aislamiento & purificación , Brotes de Enfermedades , Frecuencia de los Genes , Humanos , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos CBA , Moscú/epidemiología , Toxina del Pertussis/genética , Virulencia/genética , Tos Ferina/epidemiologíaRESUMEN
There are presented the results of genotoxicologic, immunologic and allergologic examinations which were conducted within the framework of integrated medical and biological assessment of genetically modified rootworm Diabrotica spp.--protected and glyphosate tolerant maize event MON 88017. Analysis of damages of DNA and structural chromosome aberrations, assessment of the allergenic potential and immunoreactive properties has not confirmed any genotoxic, allergenic and immunotoxic effect of maize event MON 88017.
Asunto(s)
Análisis de los Alimentos , Hipersensibilidad a los Alimentos , Alimentos Modificados Genéticamente , Plantas Modificadas Genéticamente/inmunología , Animales , Aberraciones Cromosómicas/inducido químicamente , Daño del ADN/inmunología , Resistencia a Medicamentos/genética , Análisis de los Alimentos/métodos , Hipersensibilidad a los Alimentos/inmunología , Alimentos Modificados Genéticamente/efectos adversos , Glicina/análogos & derivados , Masculino , Ratones , Pruebas de Mutagenicidad/métodos , Plantas Modificadas Genéticamente/efectos adversos , Plantas Modificadas Genéticamente/genética , Zea mays , GlifosatoRESUMEN
Protective, immunogenic, toxic, and sensitizing properties of acellular pertussis vaccine (aPV) developed according to original technology were studied, aPV had marked protective activity which lasted more than 2 years. Sera of mice immunized by aPV also possess protective properties, and they were more prominent than in sera of mice immunized by pertussis bacteria suspension (PS). Immune sera to aPV neutralized cytopathogenic effect of pertussis toxin (PT) on ovarian Chinese hamster cells in 1:250 dilution, whereas neutralizing activity of sera to PS was very low. Level of antibodies to PT was higher in rabbits immunized, according to schedules and dosage recommended for children, by aPV than by PS. High immunogenicity of aPV was proved also by levels of IgG to PT in sera of mice immunized three times by aPV in human dosage. During experiments on mice and guinea pigs aPV had mild toxicity, did not induce autoimmune process, did not have anaphylactogenic properties compared with bacterial suspension characterized by high anaphylactogenic activity. Histamine-sensitizing abilityof aPVwas 40 times lower than that of PS. Assessment of pyrogenic properties of aPV and PS performed on rabbits showed that aPV was 1,000 times less pyrogenic than PS. Obtained results demonstrate high protective and immunogenic properties of domestic acellular pertussis vaccine and its low toxic and sensitizing characteristics.
Asunto(s)
Bordetella pertussis/inmunología , Vacuna contra la Tos Ferina/administración & dosificación , Tos Ferina/inmunología , Tos Ferina/prevención & control , Anafilaxia/inducido químicamente , Animales , Anticuerpos Antibacterianos/sangre , Anticuerpos Antibacterianos/farmacología , Especificidad de Anticuerpos , Enfermedades Autoinmunes/inducido químicamente , Línea Celular , Quimera , Cricetinae , Evaluación Preclínica de Medicamentos , Femenino , Fiebre/inducido químicamente , Cobayas , Inmunoglobulina G/sangre , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos CBA , Pruebas de Neutralización , Toxina del Pertussis/agonistas , Toxina del Pertussis/inmunología , Vacuna contra la Tos Ferina/efectos adversos , Vacuna contra la Tos Ferina/toxicidad , Conejos , Vacunas Acelulares/administración & dosificación , Vacunas Acelulares/efectos adversos , Vacunas Acelulares/toxicidad , Tos Ferina/sangreRESUMEN
Strains of B. pertussis isolated from patients in Moscow in 2001-2005 as well as strains included in locally produced diphtheria-tetanus-whole cell pertussis (DTP) vaccine were studied. Nucleotide sequences in genes of pertactin and S1-subunit of pertussis toxin of isolated strains, their immunobiological properties and opportunity to use for producing of the acellular pertussis vaccine were determined. Genes of pertactin and S1-subunit of pertussis toxin in the isolated wild strains differed from the same genes in strains included in the local DTP vaccine. Majority of the isolated strains belonged to serotype 1.0.3 and were markedly virulent.
Asunto(s)
Bordetella pertussis/inmunología , Vacuna contra la Tos Ferina , Vacunación , Tos Ferina/microbiología , Alelos , Animales , Antígenos Bacterianos/genética , Antígenos Bacterianos/inmunología , Proteínas de la Membrana Bacteriana Externa/genética , Proteínas de la Membrana Bacteriana Externa/inmunología , Proteínas Bacterianas/análisis , Proteínas Bacterianas/genética , Secuencia de Bases , Bordetella pertussis/clasificación , Bordetella pertussis/genética , Bordetella pertussis/patogenicidad , Genes Bacterianos/genética , Humanos , Ratones , Moscú , Toxina del Pertussis/análisis , Toxina del Pertussis/genética , Toxina del Pertussis/inmunología , Vacuna contra la Tos Ferina/administración & dosificación , Vacuna contra la Tos Ferina/química , Vacuna contra la Tos Ferina/inmunología , Subunidades de Proteína/genética , Subunidades de Proteína/inmunología , Serotipificación , Virulencia , Factores de Virulencia de Bordetella/genética , Factores de Virulencia de Bordetella/inmunología , Tos Ferina/prevención & controlRESUMEN
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.
Asunto(s)
Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/administración & dosificación , Difteria/prevención & control , Tétanos/prevención & control , Vacunación , Tos Ferina/prevención & control , Hidróxido de Aluminio/administración & dosificación , Animales , Relación Dosis-Respuesta Inmunológica , Cobayas , Inyecciones Subcutáneas , Ratones , Compuestos Orgánicos/administración & dosificaciónRESUMEN
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.
Asunto(s)
Adyuvantes Inmunológicos/administración & dosificación , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/administración & dosificación , Inmunización , Vacunas Acelulares/administración & dosificación , Tos Ferina/prevención & control , Animales , Células Productoras de Anticuerpos/inmunología , Vacuna contra Difteria, Tétanos y Tos Ferina/administración & dosificación , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/inmunología , Relación Dosis-Respuesta Inmunológica , Evaluación Preclínica de Medicamentos , Eritrocitos/inmunología , Hipersensibilidad Tardía/etiología , Inmunidad Celular , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos CBA , Ovinos , Toxoide Estafilocócico/administración & dosificación , Vacunas Acelulares/inmunología , Tos Ferina/inmunologíaRESUMEN
As shown in this work, the synthetic immunomodulator glucosaminylmuramyldipeptide (GMDP) can be included into acellular pertussis vaccine (APV). The optimal doses of GMDP, ranging from 0.001 to 0.0001 microg, have been found. These doses enhance the protective activity of APV, especially its low-active doses. GMDP decrease the manifestations of toxic, anaphylactogenic and pyrogenic properties of APV, which may lead to the decrease of the antigenic load of APV on the body of the vaccines and thus to lessening the side-effects of vaccination. GMDP has been shown to considerably increase, in comparison with common pertussis vaccine and APV, the percentage of phagocytizing leukocytes by day 14. The immunization of mice with APV with and without GMDP in doses of 0.01 and 0.001 microg leads to a change in T-lymphocyte/B-lymphocyte ratio in the population of spleen lymphocytes.
Asunto(s)
Acetilmuramil-Alanil-Isoglutamina/análogos & derivados , Acetilmuramil-Alanil-Isoglutamina/administración & dosificación , Inmunización , Factores Inmunológicos/administración & dosificación , Vacuna contra la Tos Ferina/administración & dosificación , Tos Ferina/prevención & control , Acetilmuramil-Alanil-Isoglutamina/inmunología , Animales , Animales no Consanguíneos , Relación Dosis-Respuesta Inmunológica , Evaluación Preclínica de Medicamentos , Femenino , Fiebre/inducido químicamente , Factores Inmunológicos/inmunología , Inyecciones Intraperitoneales , Leucocitos/inmunología , Recuento de Linfocitos , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos CBA , Vacuna contra la Tos Ferina/efectos adversos , Fagocitosis , Bazo/inmunología , Vacunas Acelulares/administración & dosificación , Tos Ferina/inmunologíaRESUMEN
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.
Asunto(s)
Intestinos/patología , Hígado/patología , Pulmón/patología , Vacuna contra la Tos Ferina/farmacología , Bazo/patología , Timo/patología , Adyuvantes Inmunológicos/farmacología , Animales , Inmunidad Celular , Intestinos/inmunología , Hígado/inmunología , Pulmón/inmunología , Ratones , Especificidad de Órganos , Vacuna contra la Tos Ferina/inmunología , Bazo/inmunología , Timo/inmunología , Vacunas Acelulares/inmunología , Vacunas Acelulares/farmacologíaRESUMEN
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.
Asunto(s)
Anticuerpos Antibacterianos/biosíntesis , Bordetella pertussis/inmunología , Inmunización , Vacuna contra la Tos Ferina/inmunología , Adhesinas Bacterianas/inmunología , Animales , Anticuerpos Antibacterianos/sangre , Células CHO , Cricetinae , Pruebas de Hemaglutinación , Hemaglutininas/inmunología , Técnicas para Inmunoenzimas , Ratones , Pruebas de Neutralización , Toxina del Pertussis , Vacuna contra la Tos Ferina/administración & dosificación , Conejos , Vacunación , Vacunas Acelulares/inmunología , Vacunas de Productos Inactivados/inmunología , Factores de Virulencia de Bordetella/inmunología , Tos Ferina/prevención & controlRESUMEN
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.
Asunto(s)
Acetilmuramil-Alanil-Isoglutamina/análogos & derivados , Adyuvantes Inmunológicos/farmacología , Líquido Ascítico/citología , Macrófagos Peritoneales/efectos de los fármacos , Macrófagos Peritoneales/enzimología , Vacuna contra la Tos Ferina/farmacología , 5'-Nucleotidasa/efectos de los fármacos , Acetilmuramil-Alanil-Isoglutamina/farmacología , Adenosina Trifosfatasas/efectos de los fármacos , Animales , Relación Dosis-Respuesta a Droga , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos CBA , Vacunas de Productos Inactivados/farmacologíaAsunto(s)
Adyuvantes Inmunológicos/farmacología , Formación de Anticuerpos/efectos de los fármacos , Glicopéptidos/farmacología , Hipersensibilidad Tardía/inmunología , Animales , Relación Dosis-Respuesta Inmunológica , Eritrocitos/inmunología , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos CBARESUMEN
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.