Inmunogenicidad del antígeno ESAT-6 de Mycobacterium tuberculosis en monos búho

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Autores

Martha Calderon Carlos Parra-López Rosalba Alfonso Paola Barato Diana Giraldo Martha Pinto Manuel Patarroyo

Resumen

La ̇única vacuna disponible contra la tuberculosis es la cepaMycobacterium bovisBCG, que ofrece unaeficacia protectiva variable (0%-80%), siendo urgente un nuevo agente profil·ctico. Se han evaluado diversos candidatos a vacuna contra este patogeno, en los modelos animales de experimentaciÛn convencionales(murino, cobayo, conejo), obteniÈndose informaciÛn b·sica sobre el efecto de la vacuna en la carga bacterialfrente a un reto infeccioso, asÌ como tambiÈn la reducciÛn o prevenciÛn de la patologÌa en los pulmones uotros Ûrganos blanco; adem·s de los aspectos relacionados con la respuesta inmune hacia elMycobacteriumtuberculosis. Los primates no humanos tienen ventajas sobre los modelos convencionales en la evaluaciÛn devacunas, de hecho se ha verificado el comportamiento de agentes terapÈuticos en humanos despuÈs de habersido medida la capacidad protectiva de Èstos en monos con tuberculosis inducida. Los primates mas estudia-dos en la infección por micobacterias son el cynomulgus, y el rhesus, observ·ndose que estos animalesmantienen la infección en un estado subclÌnico, muy similar a la tuberculosis humana donde el 90% de lapoblación infectada mantiene la infecciÛn en un estado latente. Dado que el modelo animal debe semejar el comportamiento de las proteÌnas estudiadas en el ser humano, el monoAotuspuede representar ventajas enla investigación de tuberculosis por ser un primate con aproximadamente un 90% de similitud al humano encuanto a las molÈculas del sistema inmune estudiadas hasta hoy. La proteÌna ESAT-6 de (early secretoryantigenic target 6 kD) deMycobacterium tuberculosises un componente minoritario del filtrado de cultivode corto tiempo (CFP), ha sido genÈtica y quÌmicamente caracterizada e induce una potente respuestainmunogÈnica del tipo TH1. Este antÌgeno es secretado durante la fase inicial de crecimiento siendo fuerte-mente reconocido por animales y humanos infectados porMycobacterium tuberculosis, este hecho haceque su inclusiÛn en una futura vacuna anti-tuberculosis por subunidades y en pruebas de inmunodiagnÛstico.En este trabajo se estudiÛ la respuesta inmune del monoAotusfrente al antÌgeno micobacteriano ESAT-6 enforma recombinante (rESAT-6). El antÌgeno fue inmunizado junto con el adyuvante Montanide 720 producien-do una fuerte respuesta humoral y celular, no solo hacia rESAT-6 sino tambiÈn hacia la proteÌna nativa pre-sente en el filtrado de medio de cultivo deMycobacterium tuberculosis.La respuesta celular fue medidapor la incorporaciÛn de [3H]timidina en ensayos de linfoproliferaciÛn. La respuesta humoral se analizÛ porensayos de ELISA e inmunoblot, obteniÈndose altos tÌtulos de anticuerpos (hasta de 1:12,800) dirigidos rESAT-6. Se demostrÛ la naturaleza multiepitope de este antÌgeno ya que en general pÈptidos que mapean la proteÌnafueron especÌficamente reconocidos tanto a nivel celular como humoral. Se observÛ adem·s variaciÛn en larespuesta a la vacunación entre animal y animal, siendo una desventaja para un modelo de experimentación en cuanto a la predicción de la respuesta. Este estudio se constituye en un primer paso de evaluaciÛn delmonoAotuscomo modelo animal en tuberculosis.

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DOI: http://dx.doi.org/10.22490/24629448.344

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