Suppressive and additive effects in protection mediated by combinations of monoclonal antibodies specific for merozoite surface protein 1 of Plasmodium yoelii

<p>Abstract</p> <p>Background</p> <p>The merozoite surface protein (MSP)-1 is a target antigen of protective immunity and a malaria vaccine candidate. The nature of this protective immune response warrants further investigation: although specific antibody is thought to play a major role, the mechanisms of protection are still unclear. Monoclonal antibodies (mAbs) specific for the C-terminus of MSP-1 from <it>Plasmodium yoelii </it>have been shown previously to provide protection against challenge infection when administered by passive immunization to mice. Three protective mAbs were re-examined and, in particular, the effect of combinations of antibodies on the protection provided was studied. It was found that a combination of two antibodies can either provide additive protective effects or result in a suppression of protection. In this report the importance of antibody subclass and epitope specificity in the outcome of these passive immunization experiments are discussed.</p> <p>Methods</p> <p>The minimum protective dose (MPD) for each mAb was determined, and then combinations of antibody at their MPD were investigated for their ability to control parasitaemia and promote survival in groups of mice. Mice were inoculated over three days with the MPD and challenged with a blood stage infection of the virulent <it>P. yoelii </it>17 XL. The resultant parasitaemia was assessed daily on Giemsa-stained blood films. Following the infection the presence of MSP-1 specific antibodies in the sera was monitored, and the proliferative responses of cells in the spleen of protected mice were measured.</p> <p>Results</p> <p>Combining antibodies resulted in either an additive effect on protection, with reduced peak parasitaemia and better survival, or resulted in a suppression of protection over that achieved by a single antibody alone. An additive effect was observed when B6 and F5 that have the same isotype and similar fine specificity, were combined. However, a combination of mAb D3, an IgG2a, with either B6 or F5 (both IgG3) suppressed protection, an effect that may have been due to the combination of different isotypes or to the different fine specificity of the antibodies.</p> <p>Conclusions</p> <p>These results suggest that a combination of protective antibodies with either the same or different isotypes can produce either an additive or a suppressive effect in passive immunization. This phenomenon may be important in better understanding immunity in this experimental mouse model of malaria.</p

Influencia de variables ambientales sobre la presenciade Panstrongylus Geniculatus (Latreille, 1811) en domicilios del área metropolitana de Caracas, Venezuela

oai:ojs2.tesla.puertomaderoeditorial.com.ar:article/1Panstrongylus geniculatus (Latreille, 1811) (Reduviidae: Triatominae) is a hematophagous bug generally associated with the wild cycle of Trypanosoma cruzi Chagas, 1909, the etiological agent of Chagas disease. The incursions of this insect into homes located in urban and peri-urban areas cause alarm in the population and are becoming more and more frequent. As a contribution to the available knowledge on the biology and ecology of P. geniculatus as a species that transmits T. cruzi in this type of environment, the objective was to explore the influence of six environmental variables (altitude, monthly precipitation, relative humidity, average temperature , solar radiation and wind speed) on the distribution of specimens of this species captured in homes of 12 localities of the Metropolitan Area of ​​Caracas (AMC). The parasitological evaluation of the 39 insects examined showed that about 90% of them presented flagellate forms in their feces. The largest number of specimens came from collections in localities of the Miranda state (n = 32), with reports being more common during the months of May and June. Principal Component Analysis (PCA) applied to these data as an exploratory tool concentrates 60% of the variance in the first two principal components and suggests monthly precipitation (mm) and relative humidity (%) as possible environmental variables. explanations of the presence of this species in homes of the AMC.Panstrongylus geniculatus (Latreille, 1811) (Reduviidae: Triatominae) es un chinche hematófago asociado generalmente al ciclo silvestre del Trypanosoma cruzi Chagas, 1909, agente etiológico de la Enfermedad de Chagas. Las incursiones de este insecto en domicilios ubicados en zonas urbanas y periurbanas causan alarma en la población y se hacen cada vez más frecuentes. Como un aporte al conocimiento disponible sobre la biología y ecología de P. geniculatus como especie transmisora de T. cruzi en este tipo de ambientes, se propuso como objetivo explorar la influencia de seis variables ambientales (altitud, precipitación mensual, humedad relativa, temperatura media, radiación solar y velocidad del viento) sobre la distribución de especímenes de esta especie capturados en domicilios de 12 localidades del Área Metropolitana de Caracas (AMC). La evaluación parasitológica de los 39 insectos examinados mostró que cerca del 90% de ellos presentaron formas flageladas en sus heces. La mayor cantidad de ejemplares provinieron de colectas en localidades del estado Miranda (n = 32), siendo más comunes los reportes durante los meses de mayo y junio. El Análisis de Componentes Principales (ACP) aplicado a estos datos la data como herramienta exploratoria concentra en los primeros dos componentes principales un 60% de la varianza y sugiere a la precipitación mensual (mm) y la humedad relativa (%) como posibles variables ambientales explicativas de la presencia de esta especie en domicilios del AMC

Glibenclamide, a Blocker of K(+)(ATP) Channels, Shows Antileishmanial Activity in Experimental Murine Cutaneous Leishmaniasis

Glibenclamide reduced the rate of lesion growth in BALB/c mice infected with Leishmania (Leishmania) mexicana, the effect was dose dependent, and the highest dose proved more effective than glucantime. Cross-resistance to glucantime was found in animals infected with a glibenclamide-resistant line, but combined therapy reduced lesion progression even in the glibenclamide-resistant strain

Experimental heteroxenous cycle of Lagochilascaris minor Leiper, 1909 (Nematoda: Ascarididae) in white mice and in cats

Reports of natural infections of sylvatic carnivores by adult worms of species similar to Lagochilascaris minor in the Neotropical region led to attempts to estabilish experimental cycles in laboratory mice and in cats. Also, larval development was seen in the skeletal muscle of an agouti (Dasyprocta leporina) infected per os with incubated eggs of the parasite obtained from a human case. In cats, adult worms develop and fertile eggs are expelled in the feces: in mice, larval stages of the parasite develop, and are encapsulate in the skeletal muscle, and in the adipose and subcutaneous connective tissue. From our observations, we conclude that the larva infective for the mouse is the early 3rd stage, while for the final host the infective form is the later 3rd stage. A single moult was seen in the mouse, giving rise to a small population of 4th stage larvae, long after the initial infection

SPECIFIT'Y IN THE IMMUNE RESPONSE AGAINST SOMATIC ANTIGENS OF Lagochilascaris minor AND ITS RELATIONSHIPS WITH SIMILAR ANTIGENS OF Ascaris lumbricoides AND Toxocara canis

Keywords: Lagochilascaris minor, nematode, somatic antigens; specific antibodies, Ascaris lumbricoides, Toxocara canis, cross- reactivity.   RESUMEN   ESPECIFICIDAD DE LA RESPUESTA INMUNE FRENTE A LOS ANTIGENOS SOMATICOS DE Lagochilascaris minor Leiper, 1909, INTER-RELACIONES CON ANTIGENOS SIMILARES DE Ascaris lumbricoides Y Toxocara canis. Lagochilascaris minores un nematodo parásito del hombre rural de la Región Neotropical, en el cual coloniza cavidades aéreas y tejidos de la cabeza y el cuello. Se ha estudiado en primer término, antígenos somáticos y de membranas en gusanos adultos, mediante el uso de detergentes de conocida eficacia. Se obtuvieron 3 extractos proteicos a 4°C y 50.000 g, y con igual técnica, extractos de adultos de Ascaris lumbricoides y Toxocara canis, nematodos ascaridios cosmopolitas que infectan también al hombre. Las concentraciones proteicas de los extractos fueron elevadas, así, para el No 1 de L. minor, A. lumbricoides y T. canis alcanzaron 480, 1.920 y 1.305,g/ml, respectivamente, y para el N° 2 fue de 705, 1.980 y 1.785 g/ml, en el mismo orden. Anticuerpos homólogos para L. minor fueron obtenidos de una paciente con 12 años de enfermedad, y de roedores infectados experimentalmente, los cuales desarrollaron solamente estadios larvales, en sus tejidos. También se estudiaron los sueros de familiares y allegados a la paciente. Geles de Poliacrilamida en presencia de SDS (SDS-PAGE), fueron usados para el análisis electroforetico de los extractos, identificando los antígenos por la técnica de Immunoblotting. Los inmunocomplejos se identificaron por una prueba de proteína A~radioiodinada y auto-radiografía a -70°C. Los antígenos fueron enfrentados a los anticuerpos por la técnica de ouchterlony y solamente el suero·de la paciente dio 3 bandas de precipitación, con los 3 extractos de L. minor y sólo 1 con los de A. lumbricoides y T. canis. Fue demostrado un antígeno dominante en L. minor de peso molecular (p. m.) 120.000, el cual fue reconocido por todos los sueros (con excepción de un suero humano control negativo), y otro de p. m. > 200.000 el cual fue reconocido por el de la paciente, un tío, 2 hermanos y de un conejo. En la confrontación de los sueros frente antígenos de A. /umbricoides, hubo reacción con 3 de ellos, cuyos p.m. fueron > 200.000, 120.000 y 65.000. Estos resultados demuestran la existencia de anticuerpos en la paciente, sus familiares y animales infectados experimentalmente, que no son detectados por ouchterlony, siendo probable que antígenos de p. m. > 200.000 y 120.000, sean comunes a L. minor y A. /umbricoides

Amiodarone has intrinsic anti-Trypanosoma cruzi activity and acts synergistically with posaconazole

There is no effective treatment for the prevalent chronic form of Chagas' disease in Latin America. Its causative agent, the protozoan parasite Trypanosoma cruzi, has an essential requirement for ergosterol, and ergosterol biosynthesis inhibitors, such as the antifungal drug posaconazole, have potent trypanocidal activity. The antiarrhythmic compound amiodarone, frequently prescribed for the symptomatic treatment of Chagas' disease patients, has also recently been shown to have antifungal activity. We now show here for the first time that amiodarone has direct activity against T. cruzi, both in vitro and in vivo, and that it acts synergistically with posaconazole. We found that amiodarone, in addition to disrupting the parasites' Ca2+ homeostasis, also blocks ergosterol biosynthesis, and that posaconazole also affects Ca2+ homeostasis. These results provide logical explanations for the synergistic activity of amiodarone with azoles against T. cruzi and open up the possibility of novel, combination therapy approaches to the treatment of Chagas' disease using currently approved drugs.Fil: Benaim, Gustavo. Universidad Central de Venezuela, Facultad de Ciencias; Venezuela. Instituto Internacional de Estudios Avanzados; VenezuelaFil: Sanders, John M.. University of Illinois at Urbana; Estados UnidosFil: Garcia Marchán, Yael. Universidad Central de Venezuela, Facultad de Ciencias; VenezuelaFil: Colina, Claudia. Instituto Venezolano de Investigaciones Científicas; VenezuelaFil: Lira, Renee. Instituto Venezolano de Investigaciones Científicas; VenezuelaFil: Caldera, Aura R.. Instituto Venezolano de Investigaciones Científicas; VenezuelaFil: Payares, Gilberto. Universidad Central de Venezuela. Facultad de Ciencias; VenezuelaFil: Sanoja, Cristina. Universidad Central de Venezuela. Facultad de Ciencias; VenezuelaFil: Burgos, Juan Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Leon-Rossell, Annette. University of Illinois. Urbana - Champaign; Estados UnidosFil: Concepcion, Juan Luis. Universidad de los Andes; VenezuelaFil: Schijman, Alejandro Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Levin, Mariano Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Institut Cochin; FranciaFil: Oldfield, Eric. University of Illinois. Urbana - Champaign; Estados UnidosFil: Urbina, Julio A.. Instituto Venezolano de Investigaciones Científicas; Venezuel