RESUMEN
El polisacárido Vi (PsVi) de Salmonella Typhi es un antígeno T-independiente y ha demostrado ser protector en adultos jóvenes. Sin embargo, para aumentar la respuesta de anticuerpos y conferir propiedades T-dependientes al polisacárido, se ha conjugado a proteínas. Dentro de los controles exigidos por los organismos regulatorios para estas vacunas está la identidad antigénica de sus componentes y para eso se recomiendan el uso de técnicas de Resonancia Magnética Nuclear o técnicas serológicas. El objetivo del presente trabajo, fue establecer las condiciones óptimas de trabajo de un Dot Blot que permitiera determinar, rápidamente, la identidad de los antígenos en vacunas conjugadas contra S. Typhi. Para ello, se estudiaron los tiempos de incubación, las concentraciones óptimas de anticuerpo monoclonal (AcM) y del ingrediente farmacéutico activo (IFA), así como los volúmenes de aplicación óptimos para las IFAs y formulaciones vacunales, tanto para el PsVi como para el toxoide diftérico (TD). Los resultados mostraron que para la determinación de la identidad antigénica fueron suficientes 5 µL de muestras de los conjugados monovalentes en una dilución de 1/10 (vol/vol) e igual volumen para las formulaciones vacunales. Quedó demostrado que la concentración de 2,5 µg/mL para el AcM contra el PsVi y a 2 µg/mL para el AcM contra TD fueron suficientes para la determinación; mientras que los tiempos de incubación fueron ajustados a 15 min con incubación a 37 ºC. Como conclusión del trabajo se puede decir que quedaron establecidas las condiciones óptimas de trabajo para la determinación rápida de la identidad antigénica del PsVi y del TD presentes en IFA y formulaciones vacunales conjugadas(AU)
Vi polysaccharide from Salmonella Typhi is a T-independent antigen that has proven to be protective in young adults. However, it has been conjugated to proteins in order to confer T-dependent properties to the polysaccharide, and improving the antibody response. The regulatory agencies require knowing the identity of antigens included in vaccines. The Nuclear Magnetic Resonance spectroscopy and serological techniques are recommended. The aim of this work was to establish the optimal working conditions of a Dot Blot that would allow to determine quickly the identity of the antigens in conjugate vaccines against S. Typhi. The incubation times, optimum concentrations of monoclonal antibodies (MAb) and active pharmaceutical ingredient (API), as well as optimum application volumes for APIs and vaccine formulations were studied for both, PsVi and diphtheria toxoid (DT). It was proven that 5 µL of samples of the monovalent conjugates were sufficient at a dilution of 1/10 (vol/vol) and an equal volume for the vaccine formulations. It was demonstrated that the concentration of 2.5 µg/mL for the MAb against PsVi and 2 µg/mL for the MAb against DT were suitable. The incubation times were adjusted to 15 min with incubation at 37 ºC. It was established a simple and rapid method for the specific identification of PsVi and DT present in API and conjugate vaccines(AU)
Asunto(s)
Humanos , Vacunas Conjugadas/uso terapéutico , Salmonella typhi/virología , Toxoide Diftérico/uso terapéutico , Espectroscopía de Resonancia Magnética/métodos , CubaRESUMEN
Infections caused by Corynebacterium diphtheriae frequently induce situations in which very small doses of antigens injected intradermally can cause strong inflammatory reactions. This bacterium secretes the diphtheria toxin (DT), a virulence factor that can be lethal to the human organism at doses below 0.1 mg/kg of body weight. The present work proposes alternative methods of DT purification using affinity chromatography and of DT detoxification through conjugating with the polymer methoxypolyethylene glycol activated(mPEG). Tests were performed to evaluate: the formation of edemas and the presence of dermonecrotic activity, in vitro cytotoxicity to Vero cells, the neutralizing activity of serum from guinea pigs immunized with the diphtheria toxoid inactivated with mPEG, and the immunogenic activity of the purified and modified toxin. The results indicated that purification with Blue Sepharose was an efficient method, yielding antigen purity equivalent to 2600 Lf/mg of protein nitrogen. The modification of the Purified Toxin with mPEG did not result in the formation of edema or necrosis although it was immunogenic and stimulated the formation of antibodies that could neutralize the Purified Toxin. The toxoidobtained from the purified toxin maintained its immunogenic characteristics, inducing antibodies with neutralizing activity; edema and necrosis were still observed, however.
Asunto(s)
Cobayas , Difteria/microbiología , Toxina Diftérica/aislamiento & purificación , Toxina Diftérica/toxicidad , Toxoide Diftérico/administración & dosificación , Toxoide Diftérico/uso terapéutico , Cromatografía de Afinidad/métodos , Pruebas de Toxicidad/métodosRESUMEN
In 54 transplant recipients diphtheria and tetanus immunity after primary vaccination was significantly lower than in 57 control subject and 35 patients on a dialysis regimen. After a booster, tetanus antibodies developed in the transplant recipients and dialysis patients but no diphtheria antibodies developed in two transplant recipients. No adverse reactions, including acute graft rejection episodes, occurred.
Asunto(s)
Toxoide Diftérico/uso terapéutico , Difteria/prevención & control , Trasplante de Riñón , Diálisis Renal , Toxoide Tetánico/uso terapéutico , Tétanos/prevención & control , Adolescente , Adulto , Humanos , Esquemas de InmunizaciónRESUMEN
Se comentan los recientes aportes terapéuticos, dividiéndose el trabajo en los siguientes capítulos: I)Resistencia bacteriana a los diversos fármacos, en especial a la D.D.S. en su forma secundaria, así como la primaria. Dosis a emplear con la monoterapia. Causas de aparición de la resistencia (tratamiento irregular y/o bajas dosis). II) Asociación medicamentosa: sus ventajas y los principales esquemas en enfermos vírgenes y en casos de resistencia a las sulfonas. III) Tratamiento de la reacción leprosa. IV) Inmunoterapia en lepra: sus objetivos, los medios más comúnmente empleados, sus riesgos y efectos colaterales
Asunto(s)
Humanos , Lepra/tratamiento farmacológico , Lepra/terapia , Sulfonas/administración & dosificación , Sulfonas/uso terapéutico , Rifampin/administración & dosificación , Rifampin/efectos adversos , Rifampin/uso terapéutico , Farmacorresistencia Microbiana , Factor de Transferencia/uso terapéutico , Levamisol/efectos adversos , Levamisol/uso terapéutico , Vacuna BCG/efectos adversos , Vacuna BCG/uso terapéutico , Toxoide Diftérico/efectos adversos , Toxoide Diftérico/uso terapéutico , InmunoterapiaRESUMEN
Se comentan los recientes aportes terapéuticos, dividiéndose el trabajo en los siguientes capítulos: I)Resistencia bacteriana a los diversos fármacos, en especial a la D.D.S. en su forma secundaria, así como la primaria. Dosis a emplear con la monoterapia. Causas de aparición de la resistencia (tratamiento irregular y/o bajas dosis). II) Asociación medicamentosa: sus ventajas y los principales esquemas en enfermos vírgenes y en casos de resistencia a las sulfonas. III) Tratamiento de la reacción leprosa. IV) Inmunoterapia en lepra: sus objetivos, los medios más comúnmente empleados, sus riesgos y efectos colaterales
Asunto(s)
Humanos , Lepra/tratamiento farmacológico , Rifampin/administración & dosificación , Rifampin/efectos adversos , Rifampin/uso terapéutico , Sulfonas/administración & dosificación , Sulfonas/uso terapéutico , Farmacorresistencia Microbiana , Vacuna BCG/efectos adversos , Vacuna BCG/uso terapéutico , Levamisol/efectos adversos , Levamisol/uso terapéutico , Factor de Transferencia/uso terapéutico , Inmunoterapia , Lepra/terapia , Toxoide Diftérico/efectos adversos , Toxoide Diftérico/uso terapéuticoAsunto(s)
Vacuna contra la Tos Ferina/efectos adversos , Vacuna contra la Tos Ferina/uso terapéutico , Vacuna contra la Tos Ferina/toxicidad , Toxoide Diftérico/efectos adversos , Toxoide Diftérico/toxicidad , Toxoide Diftérico/uso terapéutico , Toxoide Tetánico/efectos adversos , Toxoide Tetánico/toxicidad , Toxoide Tetánico/uso terapéuticoRESUMEN
We immunized 24 patients (mean age 15.2 +/- 9.3 months) with polyribosylribitol phosphate-diphtheria toxoid conjugate vaccine (PRP-D) 2 months after a systemic Haemophilus influenzae type b infection. Children less than 24 months of age were immunized twice. Serum was obtained for antibody to PRP before and 1 or 2 months after immunization. Three of five children greater than 24 months of age and three of six children 18 to 24 months of age developed greater than 1 microgram/ml of antibody after immunization, and geometric mean postimmunization levels were significantly greater than preimmunization levels for both groups. However, two children who failed to respond to conventional PRP vaccine did not respond as expected to one dose of PRP-D. For children 7 to 17 months of age, the geometric mean PRP antibody levels increased as follows: preimmunization, 0.05 micrograms/ml; after the first dose, 0.28 micrograms/ml (p = 0.003); and after the second dose, 3.39 micrograms/ml (p = 0.001). Of 13 children, 10 developed antibody values greater than 1.0 micrograms/ml. PRP conjugate vaccines are immunogenic in young children who have not developed protective PRP antibody levels after a systemic H. Influenzae type b infection.
Asunto(s)
Anticuerpos Antibacterianos/biosíntesis , Vacunas Bacterianas/uso terapéutico , Toxoide Diftérico/uso terapéutico , Infecciones por Haemophilus/inmunología , Vacunas contra Haemophilus , Haemophilus influenzae/inmunología , Vacunas Bacterianas/administración & dosificación , Preescolar , Toxoide Diftérico/administración & dosificación , Humanos , Inmunización , Lactante , Factores de Tiempo , VacunaciónRESUMEN
At approximately 2 years of age, 27 infants previously immunized at 9 to 15 months of age with two doses of polyribosylribitol phosphate-diphtheria toxoid conjugate vaccine (PRP-D) and 23 infants immunized with polyribosylribitol phosphate (PRP) vaccine were given a single injection of PRP-D. Pre- and post-immunization sera were obtained. No serious local or systemic reactions were observed. The PRP-D recipients had a geometric mean anti-PRP antibody level of 4.8 micrograms/ml 1 month after the second primary injection, retained 1.2 microgram/ml 1 year later, and had a level of 71 micrograms/ml after the booster immunization. In contrast, PRP recipients had a geometric mean level of 0.083 microgram/ml 1 month after the second primary injection, retained 0.042 microgram/ml 1 year later, and after a single dose of PRP-D at approximately 2 years of age had a geometric mean level of 8.6 micrograms/ml. The significantly higher antibody response in the prior PRP-D recipients suggests the recall of immunologic memory induced by the PRP-D vaccine.
Asunto(s)
Vacunas Bacterianas/uso terapéutico , Toxoide Diftérico/uso terapéutico , Haemophilus influenzae/inmunología , Inmunización Secundaria , Polisacáridos/administración & dosificación , Anticuerpos Antibacterianos/inmunología , Vacunas Bacterianas/administración & dosificación , Ensayos Clínicos como Asunto , Toxoide Diftérico/administración & dosificación , Humanos , Memoria Inmunológica , LactanteAsunto(s)
Toxoide Diftérico/efectos adversos , Vacuna contra la Tos Ferina/efectos adversos , Muerte Súbita del Lactante/inducido químicamente , Toxoide Tetánico/efectos adversos , Toxoide Diftérico/uso terapéutico , Vacuna contra Difteria, Tétanos y Tos Ferina , Combinación de Medicamentos/efectos adversos , Combinación de Medicamentos/uso terapéutico , Humanos , Lactante , Vacuna contra la Tos Ferina/uso terapéutico , Muerte Súbita del Lactante/epidemiología , Tennessee , Toxoide Tetánico/uso terapéuticoRESUMEN
The capsular polysaccharide of Haemophilus influenzae type b is a poor immunogen in human infants. In an attempt to enhance immunogenicity, this polysaccharide was covalently coupled to diphtheria toxoid and the conjugate tested as a vaccine in adult volunteers. Two injections of PRP-D vaccine were given, separated by one month. The anti-PRP antibody responses in this group were compared with those in a group receiving a comparable dose (20 micrograms) of conventional PRP vaccine. Both vaccines were well tolerated. A single injection of PRP-D was significantly more immunogenic than PRP, eliciting higher serum concentrations of total anti-PRP antibody 1 month later (geo means of 248 and 62 micrograms/ml, respectively; P less than 0.001). In addition, higher concentrations of IgG anti-PRP antibody were observed in the PRP-D group (P less than 0.001). One month after reinjection of vaccine, subjects receiving PRP-D showed a small but significant decline in total antibody (P = 0.03), whereas the serum antibody concentrations in the group that received PRP remained unchanged. At 12 months, the antibody concentrations of the two groups were not significantly different. Bactericidal activity and passive protection activity (infant rat model) were tested in pooled sera from the three highest and three lowest responders in each vaccine group; both PRP and PRP-D vaccines induced biologically active anti-PRP antibody. Thus PRP-D was found to elicit biologically active serum antibody and to be more immunogenic in adults than PRP vaccine; however, the duration of higher concentrations of antibody was transient.
Asunto(s)
Formación de Anticuerpos , Vacunas Bacterianas/inmunología , Toxoide Diftérico/inmunología , Haemophilus influenzae/inmunología , Polisacáridos/inmunología , Adulto , Toxoide Diftérico/sangre , Toxoide Diftérico/uso terapéutico , Infecciones por Haemophilus/sangre , Infecciones por Haemophilus/tratamiento farmacológico , Infecciones por Haemophilus/inmunología , Humanos , Inmunoglobulina G/inmunología , Inmunoterapia/métodos , Polisacáridos/sangre , Polisacáridos/uso terapéutico , RadioinmunoensayoRESUMEN
Up to June 1963 there were 59 reported cases of diptheria. Comparison with previous years showed increasing tendency and in view of a low immune status of the population and the wide scatter of the cases throughout metropolitan Kingston, it was felt that the only effective method of control would be mass immunization aimed at the susceptible age group. The population at risk was 110,697. To cover this large number in the period of one month to enable three doses to be given at monthly intervals, hypo-jet injector guns were used and over 200,000 anti-diphtheria injections were given. This covered with significant protection over 50 percent of the target group. Since the campaign diphtheria has been considerably reduced (AU)
Asunto(s)
Humanos , Difteria/prevención & control , Toxoide Diftérico/uso terapéutico , Promoción de la Salud , Inmunización , Jamaica/epidemiologíaRESUMEN
Duración media de vida en La Rioja, San Juan y Mendoza; Ensayo de nuevas bases y orientaciones para la protección e higiene materno-infantil en el interior; Sífilis congénita y organización de la lucha contra el peligro heredo-luético; Difteria; Lucha antibociosa; Función higiénico-social del dispensario en la lucha contra la mortalidad infantil
Asunto(s)
Argentina , Sífilis Congénita/epidemiología , Difteria/epidemiología , Toxoide Diftérico/uso terapéutico , Bocio Endémico/prevención & control , Bocio/prevención & control , Esperanza de Vida , Salud Materno-Infantil , Mortalidad Infantil , Sífilis Congénita/mortalidad , Sífilis Congénita/prevención & control , Difteria/mortalidad , Toxoide Diftérico/administración & dosificación , Toxoide Diftérico/inmunología , Bocio Endémico/tratamiento farmacológico , Bocio Endémico/terapia , Bocio/tratamiento farmacológico , Bocio/terapia , Planes y Programas de Salud , Política de Salud , Promoción de la Salud , Registros Médicos , Legislación como Asunto , Atención Prenatal , Encuestas Sanitarias acerca de Suministro de Agua , Medicina Preventiva , Servicios Preventivos de Salud , Programas de Inmunización , Medicina Social , Factores Socioeconómicos , Grupos de RiesgoRESUMEN
Duración media de vida en La Rioja, San Juan y Mendoza; Ensayo de nuevas bases y orientaciones para la protección e higiene materno-infantil en el interior; Sífilis congénita y organización de la lucha contra el peligro heredo-luético; Difteria; Lucha antibociosa; Función higiénico-social del dispensario en la lucha contra la mortalidad infantil
Asunto(s)
Argentina , Bocio Endémico/prevención & control , Bocio/prevención & control , Difteria/epidemiología , Sífilis Congénita/epidemiología , Toxoide Diftérico/uso terapéutico , Bocio Endémico/terapia , Bocio Endémico/tratamiento farmacológico , Bocio/terapia , Bocio/tratamiento farmacológico , Atención Prenatal , Difteria/mortalidad , Esperanza de Vida , Factores Socioeconómicos , Grupos de Riesgo , Legislación como Asunto , Encuestas Sanitarias acerca de Suministro de Agua , Medicina Preventiva , Medicina Social , Mortalidad Infantil , Planes y Programas de Salud , Política de Salud , Programas de Inmunización , Promoción de la Salud , Registros Médicos , Salud Materno-Infantil , Servicios Preventivos de Salud , Sífilis Congénita/mortalidad , Sífilis Congénita/prevención & control , Toxoide Diftérico/administración & dosificación , Toxoide Diftérico/inmunologíaRESUMEN
Using guinea-pigs infected experimentally with human tubercle bacilli and rabbits infected experimentally with bovine tubercle bacilli, a series of studies was made to ascertain whether or not diphtheria toxoid would influence the expected course of the resultant tuberculosis. Seventhy guinea-pigs and ten rabbits were used. The administration of toxoid in relation to the inoculation of the animals with the infective agent varied in the different studies. In two groups of guinea-pigs, treatment was started the same day that the animals were infected. In another group treatment was delayed for four weeks after the animals had been infected, and in another group the guinea-pigs had received two doses of toxoid one month apart before being infected. The rabbits received the first dose of toxoid simultaneously with the infective organism. The initial dose of toxoid for the guinea-pigs was 0.1 cc. Subsequent doses were administered every two weeks, with each succeeding dose 0.05cc. greater than the preceding dose. The initial dose for rabbits was 0.2cc. This was increased by 0.1cc. at each succeeding injection, whch was at two week intervals. The toxoid was injected intramuscularly. The experiments continued until all of the animals had died, which was somewhat in excess of seven months. All of the animals died of tuberculosis, and there were no significant differences between the treated and the untreated froups. The results indicate quite convincingly that under the conditions of the experiments diphtheria toxoid failed to exert any significant deterrent effect on tuberculosis experimentally induced in guine´-pigs and in rabbits.