Caracterització de la resposta immune induïda per RUTI en el tractament de la infecció tuberculosa latent experimental

by Guirado Cáceres, Evelyn

Abstract (Summary)
It has been estimated that one third of mankind harbors a latent infection with Mycobacterium tuberculosis. In a 10% of cases a reactivation in the bacillary load will generate active tuberculosis (TB). This is especially dangerous because we dont know the mechanisms implicated in this reactivation process. In other words, we dont have prediction factors. Furthermore, the chemotherapy treatment is 9 months of isoniazida. Studies about evolution of the lung lesions in the experimental TB model in mice allowed us to generate a TB humanized model. The main purpose of this model was to generate pulmonary intragranulomatous necrosis (INPG). Initially, necrosis was generated with intranasal inoculation of LPS, but there was a high mortality associated (up to 20%). Then humanized model were standardized with aerosol infection with Mycobacterium tuberculosis strains that develop necrosis spontaneously. The new humanized model allow us to test a new immunotherapeutic strategy based on the hypothesis that after a short-term chemotherapy the vaccine RUTI (Mycobacterium tuberculosis fragmented and detoxified) is able to control bacillary reactivation, and it could be a good immunotherapeutic tool to reduce the duration of treatment. In this sense, initial studies showed that all subtypes of IgG against proteins contained in the vaccine were implied. And the immune response generated with RUTI implied a bactericidal activity in resistant (C57BL/6) and susceptible (DBA/2) mice strains. Further studies were carried out in order to evaluate humoral and cellular components of immune response generated with RUTI. Passive serum-therapy with polyclonal antibodies obtained from DBA/2 mice immunized with RUTI in immunodepressed mice model (scid) revealed a capacity to control bacillary reactivation by humoral immune response and a reduction in the presence of granulomas and abscesses. And RUTI-immunotherapy treated mice revealed the same capacity. Finally, any toxicity effects were found in RUTI vaccinated animals. Our data suggest that RUTI would be useful immunotherapeutic vaccine against Mycobacterium tuberculosis infection by triggering a wide response against a lot of peptides present both in growing and non growing bacilli.
This document abstract is also available in Catalan.
Bibliographical Information:

Advisor:Cardona i Iglesias, Pere-Joan

School:Universitat Autónoma de Barcelona

School Location:Spain

Source Type:Master's Thesis

Keywords:409 departament de genetica i microbiologia


Date of Publication:03/17/2008

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