RESUMEN
Vaccination is an effective method to prevent Newcastle disease (ND) in chickens. Marcol 52 and #10 white oil are mineral-based adjuvants and can be found in commercial inactivated ND virus vaccines. The present study demonstrated that a vegetable origin oil E515-D had lower polycyclic aromatic hydrocarbons and higher flash point than the commercial products Marcol 52 and #10 white oil. E515-D could be mixed with an aqueous phase containing ND virus antigen to form a stable water-in-oil vaccine emulsion and exhibited more potent adjuvant effects on the immune response than Marcol 52 and #10 white oil. Moreover, the absorption of E515-D-adjuvanted vaccine was faster than absorption of Marcol 52- and #10 white oil-adjuvanted vaccines when ND virus vaccines were injected in broilers. Therefore, E515-D was safe and could be a suitable adjuvant used in vaccines for food animals. In additionï¼E515-D is not easy to be flammable during shipping and storage owing to its higher flash point.
Asunto(s)
Adyuvantes Inmunológicos , Enfermedad de Newcastle , Virus de la Enfermedad de Newcastle , Panax , Saponinas , Aceite de Girasol , Vacunas Virales , Adyuvantes Inmunológicos/farmacología , Adyuvantes Inmunológicos/normas , Animales , Pollos/inmunología , Enfermedad de Newcastle/prevención & control , Virus de la Enfermedad de Newcastle/inmunología , Panax/química , Hojas de la Planta/química , Saponinas/inmunología , Saponinas/farmacología , Aceite de Girasol/química , Vacunas Virales/química , Vacunas Virales/inmunología , Vacunas Virales/normasRESUMEN
Toxoplasma gondii is an obligatory intracellular parasite, which can infect all warm-blooded animals including humans. Cytokines, including IL-15 and IL-7, play a critical role in the regulation of the homeostasis of naive and memory T cells. Co-administration the DNA vaccine with cytokines may improve its efficacy. IL-7 and IL-15 from splenic tissues of Kunming mice were cloned, and eukaryotic plasmid pVAX-IL-7-IL-15 was constructed. Kunming mice were administrated with DNA vaccine expressing T. gondii calcium-dependent protein kinase 1 (TgCDPK1), pVAX-CDPK1, in the presence or absence of IL-7 and IL-15 plasmids (pVAX-IL-7-IL-15), immune responses were analyzed including lymphoproliferative assay, cytokine and serum antibody measurements, flow cytometric surface markers on lymphocytes, and thus protective immunity against acute and chronic T. gondii infection was estimated. Mice injected with pVAX-CDPK1 supplemented with pVAX-IL-7-IL-15 showed higher Toxoplasma-specific IgG2a titers, Th1 responses associated with the production of IFN-γ, IL-2 as well as cell-mediated cytotoxic activity where stronger frequencies of IFN-γ secreting CD8+ and CD4+ T cells (CD8+/CD4+ IFN-γ+ T cells) compared to controls. Co-administration of pVAX-IL-7-IL-15 and pVAX-CDPK1 significantly (P < 0.05) increased survival time (18.07 ± 5.43 days) compared with pVAX-CDPK1 (14.13 ± 3.85 days) or pVAX-IL-7-IL-15 (11.73 ± 1.83 days) alone, and pVAX-IL-7-IL-15 + pVAX-CDPK1 significantly reduced the number of brain cysts (73.5%) in contrast to pVAX-CDPK1 (46.0%) or pVAX-IL-7-IL-15 alone (45.0%). Our results indicate that supplementation of DNA vaccine with IL-7 and IL-15 would facilitate specific humoral and cellular immune responses elicited by DNA vaccine against acute and chronic T. gondii infection in mice.
Asunto(s)
Interleucina-15/administración & dosificación , Interleucina-7/administración & dosificación , Vacunas Antiprotozoos/normas , Toxoplasma/inmunología , Toxoplasmosis/prevención & control , Vacunas de ADN/normas , Adyuvantes Inmunológicos/administración & dosificación , Adyuvantes Inmunológicos/normas , Animales , Anticuerpos Antiprotozoarios/biosíntesis , Anticuerpos Antiprotozoarios/sangre , Línea Celular , Femenino , Inmunidad Celular , Inmunoglobulina G/biosíntesis , Inmunoglobulina G/sangre , Interferón gamma/inmunología , Interleucina-15/genética , Interleucina-15/inmunología , Interleucina-7/genética , Interleucina-7/inmunología , Linfocitos/inmunología , Ratones , Plásmidos/administración & dosificación , Vacunas Antiprotozoos/administración & dosificación , Distribución Aleatoria , Organismos Libres de Patógenos Específicos , Bazo/citología , Bazo/inmunología , Análisis de Supervivencia , Toxoplasmosis/inmunología , Toxoplasmosis/mortalidad , Vacunas de ADN/administración & dosificaciónRESUMEN
Aluminum (Al) salt-based adjuvants are present in a large variety of licensed vaccines and their use is widely considered for formulations in clinical trials. Although the regulatory agencies have clearly stated the acceptable levels of Al salts in vaccines for human use, there are no general indications for preclinical research. This brief commentary reviews the current status of Al concentrations in licensed vaccines, the related potential toxicity in preclinical species, and proposes a general guideline for selection of suitable Al salt levels in preclinical models, focusing on the formulation development for recombinant protein antigens. A table with conversion factors is included in order to provide a tool for calculation of doses with different Al salts.
Asunto(s)
Adyuvantes Inmunológicos/química , Adyuvantes Inmunológicos/normas , Aluminio/química , Aluminio/normas , Vacunas/química , Vacunas/normas , Adyuvantes Inmunológicos/administración & dosificación , Aluminio/administración & dosificación , Aluminio/efectos adversos , Animales , Química Farmacéutica/métodos , Evaluación Preclínica de Medicamentos/métodos , Humanos , Vacunas/administración & dosificaciónRESUMEN
Quality control and quality assurance procedures are discussed for the agreed benchmark standard Freund's complete adjuvant (FCA). In addition, the use of the incomplete adjuvant (FIA) in the preparation of antisera is discussed. A major problem is the use of a safe and suitable mineral oil in FCA and FIA; manufacturers should provide infra-red spectra and gas liquid chromatography analyses. A range of safety tests, toxicity, pyrogenicity and endotoxin assays and advice on practical procedures for the use of these adjuvants are described.
Asunto(s)
Adyuvantes Inmunológicos/administración & dosificación , Adyuvantes Inmunológicos/normas , Adyuvante de Freund/administración & dosificación , Adyuvante de Freund/normas , Vacunación/métodos , Vacunación/normas , Animales , Modelos Animales , Control de CalidadRESUMEN
Adjuvants play an important role in the efficacy of vaccines as the antigens become more and more purified. Indeed recombinant proteins or synthetic peptides are safer than crude inactivated micro-organism, but less immunogenic. This can be balanced by specific adjuvants. But there is no universal adjuvants and their action is not yet clear and rely on different mechanisms. Then, they must be adapted according to several criteria, like the target species, the antigens, the type of immune response, the route of inoculation, or the duration of immunity. For this purpose different type of emulsions have been developed. Water in oil (W/O) emulsions induce a strong and long term immune response. Those based on mineral oils are known to be very efficient but can sometimes induce local reactions with reactive antigens. Non mineral oils are well tolerated but less efficient with poor immunogens. Multiphasic (W/O/W) emulsions can induce short and long term immune responses with various antigens and oil in water (O/W) emulsions are well tolerated and induce a short term immune response. New generation of adjuvants are based on a new concept called 'immunosol' and stem from the association of nanoparticles with a new immunostimulant. They can be used when emulsions are not suitable to obtain a good balance between safety and immunogenicity.
Asunto(s)
Adyuvantes Inmunológicos/administración & dosificación , Vacunas/administración & dosificación , Adyuvantes Inmunológicos/efectos adversos , Adyuvantes Inmunológicos/normas , Animales , Emulsiones , Humanos , Microesferas , Aceites , Control de Calidad , Seguridad , Vacunas/efectos adversos , Vacunas/normas , Drogas Veterinarias/administración & dosificación , Drogas Veterinarias/efectos adversos , Drogas Veterinarias/normas , AguaRESUMEN
In regulating vaccines, the US Food and Drug Administration (FDA) is governed by the Code of Federal Regulations. These regulations serve as the framework for product characterization, as well as preclinical and clinical testing strategies. Novel vaccine approaches such as combination vaccines, vectored vaccines, new adjuvants, and novel delivery systems pose unique regulatory challenges for the FDA. If US licensure is sought, communication with the FDA throughout the clinical development of a product is essential to identify and implement the appropriate strategies for demonstrating the safety and effectiveness of a new product.
Asunto(s)
Industria Farmacéutica/normas , United States Food and Drug Administration/legislación & jurisprudencia , United States Food and Drug Administration/tendencias , Vacunas/normas , Adyuvantes Inmunológicos/efectos adversos , Adyuvantes Inmunológicos/normas , Adyuvantes Inmunológicos/uso terapéutico , Ensayos Clínicos como Asunto/efectos adversos , Ensayos Clínicos como Asunto/normas , Sistemas de Liberación de Medicamentos/efectos adversos , Sistemas de Liberación de Medicamentos/normas , Evaluación Preclínica de Medicamentos/efectos adversos , Evaluación Preclínica de Medicamentos/normas , Vectores Genéticos/efectos adversos , Vectores Genéticos/genética , Vectores Genéticos/normas , Concesión de Licencias , Control de Calidad , Estados Unidos , Vacunas/efectos adversos , Vacunas/uso terapéutico , Vacunas Atenuadas/efectos adversos , Vacunas Atenuadas/normas , Vacunas Atenuadas/uso terapéutico , Vacunas Combinadas/efectos adversos , Vacunas Combinadas/normas , Vacunas Combinadas/uso terapéuticoRESUMEN
OBJECTIVE: To determine efficacy of vaccines incorporating QuilA, alum, dextran combined with mineral oil, or Freund adjuvant for immunization of feedlot cattle against Streptococcus bovis and Lactobacillus spp. ANIMALS: 24 steers housed under feedlot conditions. PROCEDURE: Steers were randomly assigned to 4 experimental groups and a control group. Animals in experimental groups were inoculated on days 0 and 26 with vaccines containing Freund adjuvant (FCA), QuilA, dextran combined with mineral oil (Dex), or alum as adjuvant. Serum anti-S bovis and anti-Lactobacillus IgG concentrations were measured, along with fecal pH, ruminal fluid pH, and number of S bovis and Lactobacillus spp in ruminal fluid. RESULTS: Throughout the study, serum anti-S bovis and anti-Lactobacillus IgG concentrations for animals in the Dex, QuilA, and alum groups were similar to or significantly higher than concentrations for animals in the FCA group. Serum anti-S bovis and anti-Lactobacillus IgG concentrations were significantly increased on days 26 through 75 in all 4 experimental groups, and there was a linear relationship between anti-S bovis and anti-Lactobacillus IgG concentrations. For animals in the QuilA and Dex groups, mean pH of feces throughout the period of experiment were significantly higher and numbers of S bovis and Lactobacillus spp in ruminal fluid on day 47 were significantly lower than values for control cattle. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that immunization of feedlot steers against S bovis and Lactobacillus spp with vaccines incorporating Freund adjuvant, QuilA, dextran, or alum as an adjuvant effectively induced high, long-lasting serum anti-S bovis and anti-Lactobacillus IgG concentrations. Of the adjuvants tested, dextran may be the most effective.
Asunto(s)
Adyuvantes Inmunológicos/normas , Vacunas Bacterianas/normas , Enfermedades de los Bovinos/inmunología , Lactobacillus/inmunología , Infecciones Estreptocócicas/veterinaria , Streptococcus bovis/inmunología , Adyuvantes Inmunológicos/administración & dosificación , Compuestos de Alumbre/administración & dosificación , Compuestos de Alumbre/normas , Análisis de Varianza , Animales , Anticuerpos Antibacterianos/biosíntesis , Anticuerpos Antibacterianos/sangre , Anticoagulantes/administración & dosificación , Anticoagulantes/normas , Vacunas Bacterianas/administración & dosificación , Vacunas Bacterianas/inmunología , Peso Corporal , Bovinos , Enfermedades de los Bovinos/microbiología , Enfermedades de los Bovinos/prevención & control , Dextranos/administración & dosificación , Dextranos/normas , Heces/microbiología , Adyuvante de Freund/administración & dosificación , Adyuvante de Freund/normas , Concentración de Iones de Hidrógeno , Inmunoglobulina G/biosíntesis , Inmunoglobulina G/sangre , Modelos Lineales , Masculino , Saponinas de Quillaja , Distribución Aleatoria , Rumen/microbiología , Saponinas/administración & dosificación , Saponinas/normas , Infecciones Estreptocócicas/sangre , Infecciones Estreptocócicas/inmunología , Infecciones Estreptocócicas/prevención & control , Vacunas Estreptocócicas/administración & dosificación , Vacunas Estreptocócicas/inmunología , Vacunas Estreptocócicas/normas , Vacunación/veterinariaAsunto(s)
Adyuvantes Inmunológicos/uso terapéutico , Neoplasias/tratamiento farmacológico , Preparaciones de Plantas , Proteínas de Plantas , Toxinas Biológicas/uso terapéutico , Adyuvantes Inmunológicos/efectos adversos , Adyuvantes Inmunológicos/normas , Animales , Relación Dosis-Respuesta a Droga , Humanos , Ratas , Proteínas Inactivadoras de Ribosomas Tipo 2 , Toxinas Biológicas/efectos adversos , Toxinas Biológicas/normas , Células Tumorales Cultivadas/efectos de los fármacos , Ensayo de Tumor de Célula MadreRESUMEN
Taking advantage of an unique, legally generous regulation, proprietary anthroposophic and phytotherapeutic mistletoe preparations are on the market in Germany. One constituent of the extract, the galactoside-specific lectin, is a potent biological response modifier in a very narrow low-dose range. Although the clinical implications of the lectin effects remain to be rigorously defined, this activity already prompted companies to eliminate the common batch-to-batch variations in favor of standardization, keeping the lectin content, which could otherwise vary drastically, purportedly constant. Based on literature data, immunomodulation by the lectin involves enhanced secretion of multifunctional proinflammatory cytokines such as IL-6. The apparently context-dependent ambivalence of their actions includes capacity to serve as autocrine and paracrine tumor growth and survival factors for a wide variety of tumor cell types in vitro and in vivo, as illustrated by the literature presented. The potential for clinical risks is indicated to be non-negligible, e.g. for lymphomas, advanced-stage melanomas and renal cell carcinomas. Moreover, negative effects of immunomodulatory lectin or extract treatment have already been reported. To reliably prove clinical efficacy and exclude lack of undesired side effects for each tumor class and stage, it is mandatory to evaluate the performance of this experimental therapy modality exclusively in relevant preclinical settings and strictly controlled clinical studies to obey the generally accepted rule: primum non nocere.
Asunto(s)
Adyuvantes Inmunológicos/normas , Preparaciones de Plantas , Proteínas de Plantas , Toxinas Biológicas/normas , Adyuvantes Inmunológicos/efectos adversos , Adyuvantes Inmunológicos/uso terapéutico , Citocinas/sangre , Relación Dosis-Respuesta a Droga , Aprobación de Drogas/legislación & jurisprudencia , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/inmunología , Proteínas Inactivadoras de Ribosomas Tipo 2 , Toxinas Biológicas/efectos adversos , Toxinas Biológicas/uso terapéutico , Resultado del TratamientoRESUMEN
It could be shown from several experiments that carbohydrate-binding mistletoe lectins represent the pharmacologically active constituents of mistletoe extracts. On the basis of these findings, it was possible to develop an extract preparation standardized with respect to the mistletoe lectin concentration. This drug is the first mistletoe preparation that fulfills the criteria of the guidelines for the development of drugs (1) regarding its quality and stability of the active ingredients under certain storage conditions. The quality of this preparation has also been shown in several animal models to demonstrate antitumoral potencies.
Asunto(s)
Adyuvantes Inmunológicos/uso terapéutico , Antineoplásicos Fitogénicos/uso terapéutico , Neoplasias/tratamiento farmacológico , Preparaciones de Plantas , Proteínas de Plantas , Toxinas Biológicas/uso terapéutico , Adyuvantes Inmunológicos/efectos adversos , Adyuvantes Inmunológicos/normas , Antineoplásicos Fitogénicos/efectos adversos , Antineoplásicos Fitogénicos/normas , Estabilidad de Medicamentos , Almacenaje de Medicamentos , Humanos , Estándares de Referencia , Proteínas Inactivadoras de Ribosomas Tipo 2 , Toxinas Biológicas/efectos adversos , Toxinas Biológicas/normas , Resultado del TratamientoRESUMEN
This article describes and discusses five placebo-controlled randomized studies investigating the immunomodulatory activity of preparations containing extracts of Echinacea in healthy volunteers. A total of 134 (18 female and 116 male) healthy volunteers between 18 and 40 years of age were studied. Two studies tested intravenous homeopathic complex preparations containing Echinacea angustifolia D1 (study 1) and D4 (study 5). Two studies (2 and 3a) tested oral alcoholic extracts of roots of E. purpurea, one study an extract of E. pallida roots (study 3b), and one study an extract of E. purpurea herb (study 4). Test and placebo preparations were applied for four (study 5) or five (studies 1-4) consecutive days. The primary outcome measure for immunomodulatory activity was the relative phagocytic activity of polymorphonuclear neutrophil granulocytes (PNG), measured in studies 1 and 2 with a microscopic method and in studies 3, 4, and 5 with two different cytometric methods. The secondary outcome measure was the number of leukocytes in peripheral venous blood. Safety was assessed by a screening program of blood and other objective parameters as well as by documentation of all subjective side effects. In studies 1 and 2 the phagocytic activity of PNG was significantly enhanced compared with placebo [maximal stimulation 22.7% (95% confidence interval 17.5-27.9%) and 54.0% (8.4-99.6%), respectively], while in the other studies no significant effects were observed. Analysis of intragroup differences revealed significant changes in phagocytic activity during the observation periods in five test and three control groups. Leukocyte number was not influenced significantly in any study. Side effects due to the test preparations could not be detected. Our studies provide evidence for immunomodulatory activity of the homeopathic combination tested in study 1 and the E. purpureae radix extract tested in study 2. The negative results of the other three studies are difficult to interpret due to the different methods for measuring phagocytosis, the relevant changes in phagocytic activity within most placebo and treatment groups during the observation period, and the small sample sizes. Future studies should be performed on patients rather than healthy volunteers and use standardized or chemically defined monopreparations of Echinacea.
Asunto(s)
Adyuvantes Inmunológicos/normas , Antiinflamatorios no Esteroideos/inmunología , Granulocitos/efectos de los fármacos , Homeopatía/normas , Recuento de Leucocitos/efectos de los fármacos , Neutrófilos/efectos de los fármacos , Fagocitosis/efectos de los fármacos , Extractos Vegetales/inmunología , Adyuvantes Inmunológicos/química , Adolescente , Adulto , Antiinflamatorios no Esteroideos/química , Química Farmacéutica , Método Doble Ciego , Echinacea , Femenino , Citometría de Flujo , Humanos , Masculino , Extractos Vegetales/química , Método Simple CiegoAsunto(s)
Adyuvantes Inmunológicos/normas , Evaluación Preclínica de Medicamentos/métodos , Acetilmuramil-Alanil-Isoglutamina/farmacología , Adyuvantes Inmunológicos/uso terapéutico , Adyuvantes Inmunológicos/toxicidad , Amantadina/análogos & derivados , Amantadina/farmacología , Animales , Replicación del ADN/efectos de los fármacos , Dipéptidos/farmacología , Relación Dosis-Respuesta Inmunológica , Evaluación Preclínica de Medicamentos/normas , Reacción Injerto-Huésped/efectos de los fármacos , Inmunoterapia , Inflamación/inducido químicamente , Ratones , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Relación Estructura-Actividad , Timidina Quinasa/antagonistas & inhibidoresRESUMEN
The water-in-oil-in-water (w/o/w) emulsion showed potent adjuvant effect on the antibody formation to thymus-dependent antigens, but not to thymus-independent antigens. In hapten-carrier system the priming with carrier in the w/o/w emulsion enhanced more effectively the carrier specific helper function than did the priming with carrier in free solution. The cells responsible for the helper function were radioresistant. In the adoptive cell transfer system, the w/o/w emulsion was shown to enhance helper cell function. It is discussed that our w/o/w emulsion exerts the adjuvant effect by enhancing helper T cell activity.