RESUMO
Intramammary infections in cattle resulting in mastitis have detrimental effects on cows' well-being, lifespan and milk production. In the host defense against S. aureus mastitis antibodies are thought to play an important role. To explore potential ways to increase antibody titers in the bovine mammary gland the effects of various adjuvants on the magnitude, isotype, and neutralizing capacity of antibodies produced following subcutaneous vaccine administration at different immunization sites were analyzed. In this study, α-toxoid was used as a model antigen and formulated in three different alum-based adjuvants: Alum-Saponin, Alum-Oil, and Alum-Saponin-Oil. Vaccines were administered near the suspensory ligament of the udder or in the lateral triangular area of the neck. At both immunization sites, immunization with α-toxoid in Alum-Saponin-Oil resulted in higher specific antibody titers in milk and serum as compared with Alum-Oil and Alum-Saponin, without favoring an IgG1, IgG2, or IgA response. Furthermore, the neutralizing capacity of milk serum and serum following immunization near the udder and in the neck was higher when Alum-Saponin-Oil was used as adjuvant compared with Alum-Oil and Alum-Saponin. Prime immunizations near the udder effectively increased both antibody isotype titers and neutralization titers, while prime plus boost immunizations were required to induce similar effects following immunization in the neck. Results indicate that subcutaneous administration of an Alum-Saponin-Oil based vaccine near the udder could be further explored for the development of a one-shot vaccination strategy to efficiently increase intramammary antibody responses.
Assuntos
Adjuvantes Imunológicos/farmacologia , Bovinos/imunologia , Glândulas Mamárias Animais/imunologia , Leite/imunologia , Toxoide Estafilocócico/administração & dosagem , Vacinação/veterinária , Adjuvantes Imunológicos/análise , Animais , Formação de Anticorpos , Feminino , Injeções Subcutâneas/veterinária , Pescoço , Vacinação/métodosRESUMO
Staphylococcus aureus causes significant illnesses throughout the world, including toxic shock syndrome (TSS), pneumonia, and infective endocarditis. Major contributors to S. aureus illnesses are secreted virulence factors it produces, including superantigens and cytolysins. This study investigates the use of superantigens and cytolysins as staphylococcal vaccine candidates. Importantly, 20% of humans and 50% of rabbits in our TSS model cannot generate antibody responses to native superantigens. We generated three TSST-1 mutants; G31S/S32P, H135A, and Q136A. All rabbits administered these TSST-1 toxoids generated strong antibody responses (titers>10,000) that neutralized native TSST-1 in TSS models, both in vitro and in vivo. These TSST-1 mutants lacked detectable residual toxicity. Additionally, the TSST-1 mutants exhibited intrinsic adjuvant activity, increasing antibody responses to a second staphylococcal antigen (ß-toxin). This effect may be due to TSST-1 mutants binding to the immune co-stimulatory molecule CD40. The superantigens TSST-1 and SEC and the cytolysin α-toxin are known to contribute to staphylococcal pneumonia. Immunization of rabbits against these secreted toxins provided complete protection from highly lethal challenge with a USA200 S. aureus strain producing all three exotoxins; USA200 strains are common causes of staphylococcal infections. The same three exotoxins plus the cytolysins ß-toxin and γ-toxin contribute to infective endocarditis and sepsis caused by USA200 strains. Immunization against these five exotoxins protected rabbits from infective endocarditis and lethal sepsis. These data suggest that immunization against toxoid proteins of S. aureus exotoxins protects from serious illnesses, and concurrently superantigen toxoid mutants provide endogenous adjuvant activity.
Assuntos
Toxinas Bacterianas/imunologia , Citotoxinas/imunologia , Proteínas Hemolisinas/imunologia , Coelhos/imunologia , Infecções Estafilocócicas/terapia , Staphylococcus aureus/imunologia , Superantígenos/imunologia , Adjuvantes Imunológicos/administração & dosagem , Animais , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/imunologia , Formação de Anticorpos , Proteínas de Bactérias/imunologia , Toxinas Bacterianas/administração & dosagem , Antígenos CD40/imunologia , Linhagem Celular , Citotoxinas/administração & dosagem , Endocardite Bacteriana/imunologia , Endocardite Bacteriana/microbiologia , Endocardite Bacteriana/terapia , Exotoxinas/imunologia , Feminino , Proteínas Hemolisinas/administração & dosagem , Humanos , Masculino , Testes de Neutralização , Pneumonia Estafilocócica/imunologia , Pneumonia Estafilocócica/microbiologia , Pneumonia Estafilocócica/terapia , Coelhos/microbiologia , Choque Séptico/imunologia , Choque Séptico/microbiologia , Choque Séptico/terapia , Infecções Estafilocócicas/imunologia , Infecções Estafilocócicas/microbiologia , Toxoide Estafilocócico/administração & dosagem , Toxoide Estafilocócico/imunologia , Vacinas Antiestafilocócicas/imunologia , Staphylococcus aureus/patogenicidade , Superantígenos/administração & dosagem , VacinaçãoRESUMO
The preservative thimerosal contains ethyl mercury (EtHg). Concerns over possible toxicity have re-emerged recently due to its presence in (swine and other) flu vaccines. We examined the potential accumulation of mercury in adults given repeated injections of a thimerosal-preserved vaccine for many years. Fifteen female patients were recruited from an outpatient clinic running a clinical trial with repeated injections (1 ml every 3-4 weeks) of a staphylococcus toxoid vaccine containing 0.01% thimerosal to treat chronic fatigue syndrome. Fifteen untreated female patients with the same diagnoses served as controls. Blood samples were taken before injecting the vaccine, 1 day later, about 2 weeks later, and just before the next injection. In the 15 controls, samples were taken twice. Blood was analyzed for total mercury and EtHg. The toxicokinetics were assessed for each patient separately as well as with a population-based pharmacokinetic model. Total mercury in blood increased on Day 1 in all treated patients (median: 0.33, range: 0.17-1.3 µg/l), as did EtHg (median: 0.14 µg/l, range: 0.06-0.43 µg/l). After a few weeks, levels were back to normal and similar to those in controls. Levels of methyl mercury (MeHg; from fish consumption) were much higher than those of EtHg. After exclusion of an outlier, the mean half-life in a population-based model was 5.6 (95% CI: 4.8-6.3) days. The results indicate that mercury from thimerosal is not accumulated in blood in adults. This is in accordance with short half-lives and rapid metabolism of EtHg to inorganic mercury.
Assuntos
Mercúrio/sangue , Conservantes Farmacêuticos/farmacocinética , Toxoide Estafilocócico/farmacocinética , Timerosal/farmacocinética , Adulto , Idoso , Ensaios Clínicos como Assunto , Feminino , Meia-Vida , Humanos , Injeções Subcutâneas , Masculino , Mercúrio/toxicidade , Compostos de Metilmercúrio/sangue , Compostos de Metilmercúrio/toxicidade , Pessoa de Meia-Idade , Conservantes Farmacêuticos/química , Toxoide Estafilocócico/administração & dosagem , Toxoide Estafilocócico/química , Timerosal/sangue , Timerosal/química , Fatores de TempoRESUMO
Immunomodulators licopid (synthetic analogue of muramylpeptide) and purified staphylococcal toxoid (PST) in some variants of experiments on mice caused adverse immunologic effects: enhancement of virus-induced immunosupression, shift from latent immunosupression (revealed only by low, but not standard, doses of test-antigen) to manifested one. Described adverse effects are not a contraindication for use of the studied drugs in practice. Their adverse effects were revealed only after single inoculation, whereas in clinical conditions PST and licopid are used by courses with duration of 5-7 and 10 days respectively. Our experiments show that inoculation of suppressive doses of the preparations repeated by 2-4 times can prevent the shift from latent to manifested immunosupression. Enhancement of immunosupression was not observed in case of combined administration of suppressive doses of PST and adjuvant dose of licopid.
Assuntos
Acetilmuramil-Alanil-Isoglutamina/análogos & derivados , Hospedeiro Imunocomprometido/imunologia , Fatores Imunológicos/efeitos adversos , Terapia de Imunossupressão , Toxoide Estafilocócico/efeitos adversos , Acetilmuramil-Alanil-Isoglutamina/administração & dosagem , Acetilmuramil-Alanil-Isoglutamina/efeitos adversos , Acetilmuramil-Alanil-Isoglutamina/imunologia , Animais , Células Produtoras de Anticorpos/imunologia , Relação Dose-Resposta Imunológica , Esquema de Medicação , Vírus da Encefalite da Califórnia/imunologia , Enterovirus/imunologia , Fatores Imunológicos/administração & dosagem , Injeções Intraperitoneais , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos CBA , Toxoide Estafilocócico/administração & dosagem , Toxoide Estafilocócico/imunologia , Fatores de TempoRESUMO
With adaptive transfer method it has been shown that immunomodulator purified staphylococcal toxoid (PST) changed (stimulate or suppress) antigen-presenting function (APF) of mice peritoneal macrophages (MF) in vivo. This phenomenon was registered during assessment of ability of peritoneal MF to present heterologous (with regard to PST) antigen--sheep erythrocytes (SE). Modulation vector depended from time interval between PST and SE inoculations. Inoculation of PST 1.5 h before SE resulted in stimulation of APF. When SE were inoculated to donor mice 24 h after PST, suppression of APF was developed. Suppression of APF was observed along with suppression of proinflammatory cytokines (IL-1beta, IL-6, TNF-alpha) as well as B-lymphocytes growth factor (IL-4). When cytokine profile was assessed 4 h after PST injection, the suppression of synthesis of these cytokines was not observed. Production of IL-12 increased in 9-12 times in 4 and 24 h after PST injection.
Assuntos
Citocinas/biossíntese , Macrófagos Peritoneais/imunologia , Toxoide Estafilocócico/imunologia , Animais , Apresentação de Antígeno , Eritrócitos/imunologia , Interleucina-12/biossíntese , Interleucina-1beta/biossíntese , Interleucina-4/biossíntese , Interleucina-6/biossíntese , Masculino , Camundongos , Camundongos Endogâmicos CBA , Ovinos , Toxoide Estafilocócico/administração & dosagem , Fatores de Tempo , Fator de Necrose Tumoral alfa/biossínteseRESUMO
Effect of immunomodulators for microbial origin on innate immunity and antitumor system was continued to study. Immunomodificator Immunovac VP-4, purified staphylococcal toxoid and glucosaminyl muramyl dipeptide (GMDP) equally enhanced cytotoxicity of mononuclear leukocytes of peripheral blood of healthy donors. Index of cytotoxicity was 2.78, 2.77 and 2.70 respectively. Reduced metastatic progression of Lewis lung carcinoma in mice was observed after Immunovac VP-4 and GMDP administration. Effectiveness was seen when preparations administered according to schedules including their administration before implantation of the tumor. If preparations were administered number of metastases reduced in 4.4-5.6 times and size of metastases reduced in 7-10 times. Interplay between antitumor activity of studied immunomodulators and cytotoxic activity of NK-cells, which are base effectors of antitumor immune response, are discussed.
Assuntos
Acetilmuramil-Alanil-Isoglutamina/análogos & derivados , Adjuvantes Imunológicos/uso terapêutico , Vacinas Bacterianas/imunologia , Vacinas Bacterianas/uso terapêutico , Carcinoma Pulmonar de Lewis/tratamento farmacológico , Fatores Imunológicos/imunologia , Leucócitos Mononucleares/imunologia , Neoplasias Pulmonares/tratamento farmacológico , Toxoide Estafilocócico/imunologia , Toxoide Estafilocócico/uso terapêutico , Vacinas Combinadas/imunologia , Vacinas Combinadas/uso terapêutico , Acetilmuramil-Alanil-Isoglutamina/imunologia , Acetilmuramil-Alanil-Isoglutamina/uso terapêutico , Adjuvantes Imunológicos/administração & dosagem , Animais , Vacinas Bacterianas/administração & dosagem , Carcinoma Pulmonar de Lewis/patologia , Carcinoma Pulmonar de Lewis/secundário , Testes Imunológicos de Citotoxicidade , Esquema de Medicação , Humanos , Injeções Intraperitoneais , Células K562 , Pulmão/patologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/secundário , Camundongos , Camundongos Endogâmicos C57BL , Metástase Neoplásica/tratamento farmacológico , Toxoide Estafilocócico/administração & dosagem , Vacinas Combinadas/administração & dosagemRESUMO
Chronic experiments lasting for 5 weeks were carried out in 40 nonpedigree mature dogs. It has been detected that preliminary immunization with staphylococcus anatoxin potentiates the compensation mechanisms in the course of postresuscitation period, stimulates cell proliferation by increasing cardiac output that is an adaptive reaction of the cardiovascular system in postresuscitation period and provides optimal metabolism of the organism.
Assuntos
Débito Cardíaco/efeitos dos fármacos , Imunização , Ressuscitação , Toxoide Estafilocócico/uso terapêutico , Animais , Proliferação de Células/efeitos dos fármacos , Cães , Miocárdio/patologia , Choque Hemorrágico/terapia , Toxoide Estafilocócico/administração & dosagemRESUMO
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.
Assuntos
Adjuvantes Imunológicos/administração & dosagem , Vacinas contra Difteria, Tétano e Coqueluche Acelular/administração & dosagem , Imunização , Vacinas Acelulares/administração & dosagem , Coqueluche/prevenção & controle , Animais , Células Produtoras de Anticorpos/imunologia , Vacina contra Difteria, Tétano e Coqueluche/administração & dosagem , Vacinas contra Difteria, Tétano e Coqueluche Acelular/imunologia , Relação Dose-Resposta Imunológica , Avaliação Pré-Clínica de Medicamentos , Eritrócitos/imunologia , Hipersensibilidade Tardia/etiologia , Imunidade Celular , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos CBA , Ovinos , Toxoide Estafilocócico/administração & dosagem , Vacinas Acelulares/imunologia , Coqueluche/imunologiaRESUMO
Interaction peculiarities of three components of the immune human homeostasis-antigens of blood groups AB0, staphylococcus antigens and antistaphylococcus antibodies have been investigated. Donors (85) of antistaphylococcus plasma immunized by staphylococcus anatoxin have been investigated. It is found that the nasal staphylococcus carriage in donors depends on the level of specific and natural antibodies and on the coincidence between the staphylococcus antigen structure and the protein substance of the specific blood group factors.
Assuntos
Sistema ABO de Grupos Sanguíneos/imunologia , Anticorpos Antibacterianos/sangue , Doadores de Sangue , Mucosa Nasal/microbiologia , Infecções Estafilocócicas/microbiologia , Staphylococcus/imunologia , Portador Sadio , Humanos , Infecções Estafilocócicas/sangue , Infecções Estafilocócicas/prevenção & controle , Toxoide Estafilocócico/administração & dosagem , Staphylococcus/isolamento & purificação , VacinaçãoRESUMO
On the 50 volunteers from 20 to 40 years old gomeostasis indexes of inoculating by staphylococci cleaning adsorbing anatoxini donors, before have been revactinated against tetanus, were studied. It was established, that attract of plasmaferes donors to consistent immunization by tetani and staphylococci anatoxini don't call negative alterations in their gomeostasis indexes. Results of study demonstrate, that it's possibly to attract for immunization by staphylococci anatoxini donors, before have been revactinated against tetanus.
Assuntos
Doadores de Sangue , Homeostase/imunologia , Toxoide Estafilocócico/administração & dosagem , Vacinas Antiestafilocócicas/administração & dosagem , Toxoide Tetânico/administração & dosagem , Adulto , Anticorpos Antibacterianos/sangue , Humanos , Imunização , Toxoide Estafilocócico/efeitos adversos , Toxoide Estafilocócico/imunologia , Vacinas Antiestafilocócicas/efeitos adversos , Vacinas Antiestafilocócicas/imunologia , Toxoide Tetânico/efeitos adversos , Toxoide Tetânico/imunologiaRESUMO
The action of immunomodulators, purified staphylococcal toxoid (PST) and lycopid, on secondary immunodeficiency state developing during infection caused by Coxsackie virus B3 was studied. This defect was manifested by delayed hypersensitivity to sheep red blood cells (SRBC) and the suppression of neutralizing antibodies to poliomyelitis virus. Depending on the scheme of the experiment, PST normalized the defects of immune response to SRBC or poliovirus, increased suppression or showed no activity. Lycopid corrected the defects of humoral response to SRBC. The combination of PST and lycopid was found to produce no increase of suppression. The suggestion was made on the expediency of combination of two (and probably more) immunomodulators for increasing the efficiency of correction of secondary immunodeficiency.
Assuntos
Acetilmuramil-Alanil-Isoglutamina/análogos & derivados , Acetilmuramil-Alanil-Isoglutamina/imunologia , Enterovirus Humano B , Infecções por Enterovirus/imunologia , Imunidade/imunologia , Toxoide Estafilocócico/imunologia , Acetilmuramil-Alanil-Isoglutamina/administração & dosagem , Adjuvantes Imunológicos/administração & dosagem , Animais , Terapia de Imunossupressão , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos CBA , Camundongos Endogâmicos DBA , Toxoide Estafilocócico/administração & dosagemRESUMO
In this study, the adjuvant effect of the sustained release biodegradable nanospheres (100-150 nm in diameter) has been compared with alum. Nanospheres were formulated using a biodegradable polylactic polyglycolic acid copolymer (PLGA, 50:50) containing Staphylococcal Enterotoxin B (SEB) toxoid as a model vaccine antigen. Systemic immune response of the nanospheres containing toxoid was studied in rabbits by subcutaneous immunization. The data demonstrated that approximately 30% of the toxoid activity was lost following its encapsulation into nanospheres. Under in vitro conditions, nanospheres demonstrated sustained release of the toxoid. However, only 20% of the antigenic toxoid was released over the first 2 weeks of the release study. Immunization of animals with equal doses of toxoid, either using nanospheres or alum induced a comparable systemic immune response (IgG, IgM and IgA). The immune response reached a maximum level at 7 weeks post-immunization, which then gradually declined with time. The booster dose of toxoid at 19 weeks, either using alum or nanospheres induced similar immune response in both the groups, but was greater than the primary immune response. The studies, thus, suggest that biodegradable nanospheres could be used as a vaccine adjuvant.
Assuntos
Adjuvantes Imunológicos/administração & dosagem , Compostos de Alúmen/química , Enterotoxinas/química , Enterotoxinas/imunologia , Toxoide Estafilocócico/química , Toxoide Estafilocócico/imunologia , Compostos de Alúmen/administração & dosagem , Animais , Biodegradação Ambiental , Relação Dose-Resposta Imunológica , Portadores de Fármacos , Estabilidade de Medicamentos , Eletroforese em Gel de Poliacrilamida , Enterotoxinas/administração & dosagem , Ensaio de Imunoadsorção Enzimática , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Injeções Subcutâneas , Masculino , Microscopia Eletrônica de Varredura , Microesferas , Tamanho da Partícula , Coelhos , Toxoide Estafilocócico/administração & dosagemRESUMO
The paper presents one clinical study effected by fourty-four patients with endogenous uveitis which beneficiary of a general treatment with staphylococcal anatoxin. The conclusions of the study impose that one effective treatment is obtained at the young patients with anterior, acute uveitis with moderate inflammatory phenomenon and what present one effective answer of the lymphocyte T by interleukin 1. The application of the treatment suppose several exams reminiscent of the immunologic status especially of the cellular immunology.
Assuntos
Toxoide Estafilocócico/administração & dosagem , Uveíte Anterior/tratamento farmacológico , Doença Aguda , Adolescente , Adulto , Criança , Feminino , Humanos , Imunidade Celular/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Fatores de Tempo , Uveíte Anterior/imunologiaAssuntos
Adjuvantes Imunológicos/administração & dosagem , Vírus da Encefalite da Califórnia , Encefalite da Califórnia/terapia , Toxoide Estafilocócico/administração & dosagem , Adjuvantes Imunológicos/efeitos adversos , Animais , Avaliação Pré-Clínica de Medicamentos , Encefalite da Califórnia/imunologia , Tolerância Imunológica/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos CBA , Toxoide Estafilocócico/efeitos adversos , Fatores de TempoRESUMO
Purified staphylococcal toxoid (PST) was shown to be capable of preventing the development of secondary antigen-nonspecific immune deficiency in mice, immunized with whole-cell pertussis vaccine. The immunocorrective action of PST was manifested after its injection before (on day -1), simultaneously with and after (on day +1) the injection of whole-cell pertussis vaccine. Correction was either complete or partial, depending on the scheme of the experiment and the dose of PST.
Assuntos
Adjuvantes Imunológicos/administração & dosagem , Síndromes de Imunodeficiência/tratamento farmacológico , Vacina contra Coqueluche/efeitos adversos , Toxoide Estafilocócico/administração & dosagem , Animais , Células Produtoras de Anticorpos/efeitos dos fármacos , Células Produtoras de Anticorpos/imunologia , Relação Dose-Resposta Imunológica , Avaliação Pré-Clínica de Medicamentos , Eritrócitos/imunologia , Síndromes de Imunodeficiência/induzido quimicamente , Síndromes de Imunodeficiência/imunologia , Injeções Intraperitoneais , Camundongos , Camundongos Endogâmicos CBA , Vacina contra Coqueluche/administração & dosagem , Baço/efeitos dos fármacos , Baço/imunologia , Fatores de TempoAssuntos
Anemia/terapia , Transfusão de Sangue/métodos , Transfusão de Eritrócitos , Abscesso Pulmonar/terapia , Substitutos do Plasma/administração & dosagem , Pneumonia Estafilocócica/terapia , Toxoide Estafilocócico/administração & dosagem , Anemia/etiologia , Criança , Terapia Combinada , Humanos , Abscesso Pulmonar/sangue , Abscesso Pulmonar/complicações , Pneumonia Estafilocócica/sangue , Pneumonia Estafilocócica/complicaçõesAssuntos
Empiema Pleural/terapia , Imunoterapia/métodos , Interferon-alfa/biossíntese , Leucócitos/metabolismo , Abscesso Pulmonar/terapia , Osteomielite/terapia , Infecções Estafilocócicas/terapia , Toxoide Estafilocócico/administração & dosagem , Adolescente , Criança , Pré-Escolar , Empiema Pleural/imunologia , Humanos , Lactente , Interferon-alfa/imunologia , Leucócitos/imunologia , Abscesso Pulmonar/imunologia , Osteomielite/imunologia , Infecções Estafilocócicas/imunologiaRESUMO
Microspheres composed of biocompatible, biodegradable poly(DL-lactide-co-glycolide) (DL-PLG) and staphylococcal enterotoxin B (SEB) toxoid were evaluated as a vaccine delivery system when subcutaneously injected into mice. As measured by circulating immunoglobulin G (IgG) antitoxin titers, the delivery of SEB toxoid via DL-PLG microspheres, 1 to 10 microns in diameter, induced an immune response which was approximately 500 times that seen with nonencapsulated toxoid. The kinetics, magnitude, and duration of the antitoxin response induced with microencapsulated toxoid were similar to those obtained when an equal toxoid dose was administered as an emulsion with complete Freund adjuvant. However, the microspheres did not induce the inflammation and granulomata formation seen with complete Freund adjuvant. The adjuvant activity of the microspheres was not dependent on the superantigenicity of SEB toxin and was equally effective at potentiating circulating IgG antitrinitrophenyl levels in response to microencapsulated trinitrophenyl-keyhole limpet hemocyanin. Empty DL-PLG microspheres were not mitogenic, and SEB toxoid injected as a mixture with empty DL-PLG microspheres was no more effective as an immunogen than toxoid alone. Antigen-containing microspheres 1 to 10 microns in diameter exhibited stronger adjuvant activity than those greater than 10 microns, which correlated with the delivery of the 1- to 10-microns, but not the greater than 10-microns, microspheres into the draining lymph nodes within macrophages. The antibody response induced through immunization with microencapsulated SEB toxoid was protective against the weight loss and splenic V beta 8+ T-cell expansion induced by intravenous toxin administration. These results show that DL-PLG microsphere vaccine delivery systems, which are composed of pharmaceutically acceptable components, possess a strong adjuvant activity for their encapsulated antigens.
Assuntos
Adjuvantes Imunológicos , Anticorpos Antibacterianos/biossíntese , Materiais Biocompatíveis , Enterotoxinas/imunologia , Ácido Láctico , Ácido Poliglicólico , Polímeros , Toxoide Estafilocócico/imunologia , Staphylococcus aureus/imunologia , Adjuvantes Imunológicos/administração & dosagem , Animais , Biodegradação Ambiental , Portadores de Fármacos , Enterotoxinas/administração & dosagem , Feminino , Imunoglobulina G/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Microesferas , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Toxoide Estafilocócico/administração & dosagem , Linfócitos T/imunologiaRESUMO
The protective potency of purified staphylococcal toxoid by the survival rate of immunized mice challenged with the culture of Staphylococcus aureus strain L-1726 and the antigenic properties of the toxoid, determined by the level of antitoxin in the blood of mice and by the intensity of cell-mediated immunity in the spleen-cell migration inhibition test, were studied. The experiments were made on CBA and C57BL/6 mice. Purified staphylococcal toxoid was shown to possess antigenic and protective properties in a wide range of doses between 0.15 and 15 binding units per mouse. The protective effect of the toxoid in CBA mice was manifested in the presence of circulating antibodies and cell-mediated reaction or only in the presence of the toxoid. In C57BL/6 mice the protective effect of the toxoid was less pronounced and appeared in combination with the induction of cell-mediated immunity in the presence of an extremely low antibody level (0.062 I.U.).