Mycobacterium tuberculosisESAT-6 antigen immunogenicity in Owl Monkeys
Mycobacterium tuberculosisESAT-6 antigen immunogenicity in Owl Monkeys
Mycobacterium tuberculosisESAT-6 antigen immunogenicity in Owl Monkeys
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La única vacuna disponible contra la tuberculosis es la cepa Mycobacterium bovis BCG, que ofrece una eficacia protectiva variable (0%-80%), siendo urgente un nuevo agente profiláctico. Se han evaluado diversos candidatos a vacuna contra este patógeno, en los modelos animales de experimentación convencionales (murino, cobayo, conejo), obteniéndose información básica sobre el efecto de la vacuna en la carga bacterial frente a un reto infeccioso, así como también la reducción o prevención de la patología en los pulmones u otros órganos blanco; además de los aspectos relacionados con la respuesta inmune hacia el Mycobacterium tuberculosis. Los primates no humanos tienen ventajas sobre los modelos convencionales en la evaluación de vacunas, de hecho se ha verificado el comportamiento de agentes terapéuticos en humanos después de haber sido medida la capacidad protectiva de éstos en monos con tuberculosis inducida. Los primates más estudiados en la infección por micobacterias son el cynomulgus, y el rhesus, observándose que estos animales mantienen la infección en un estado subclínico, muy similar a la tuberculosis humana donde el 90% de la población infectada mantiene la infección en un estado latente.Dado que el modelo animal debe semejar el comportamiento de las proteínas estudiadas en el ser humano, el mono Aotus puede representar ventajas en investigación de tuberculosis por ser un primate con aproximadamente un 90% de similitud al humano en cuanto a las moléculas del sistema inmune estudiadas hasta hoy. La proteína ESAT-6 de (early secretory antigenic target 6 kD) de Mycobacterium tuberculosis es un componente minoritario del filtrado de cultivo de corto tiempo (CFP), ha sido genética y químicamente caracterizada e induce una potente respuesta inmunogénica del tipo TH1. ... Several ESAT-6-based vaccines have been widely studied in different animal models, presenting potent ability to induce both cellular and humoral responses. As ESAT-6 is a well-characterized mycobacterial antigen, its capacity to induce immune responses in a nonhuman primate model has been evaluated. The immunization of recombinant ESAT-6 (rESAT-6) in Aotus nancymaae monkeys has elicited a strong cellular response, not just to rESAT-6, but also to the native protein present in Mycobacterium tuberculosis culture filtrate proteins measured as [3H]thymidine incorporation in lymphocyte proliferation assays. High humoral response was also observed, having antibody titers of 1:12,800 directed towards rESAT-6. The protein.s multi-epitope nature was further demonstrated since several peptide sequences were specifically recognized at both cellular and humoral level. The high immunogenicity observed, as well as the relatively high characterization of the Aotus. immune system at molecular level, are two advantage to propose Aotus nancymaae as animal model for studying M. tuberculosis infection; however, our results reveal an animal-to-animal variation in response to vaccination, this could be a disadvantage
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