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Vol. 42. Issue 1.
Pages 25-32 (January 2006)
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Vol. 42. Issue 1.
Pages 25-32 (January 2006)
Review Article
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Origin and Development of RUTI, a New Therapeutic Vaccine Against Mycobacterium tuberculosis Infection
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P.J. Cardonaa,b,
Corresponding author
pcardona@ns.hugtip.scs.es

Correspondence: Dr. P.J. Cardona. Unitat de Tuberculosi Experimental. Servei de Microbiologia. Hospital Universitari Germans Trias i Pujol. Ctra. del Canyet, s/n. 08916 Badalona. Barcelona. España
, I. Amata,b
a Unitat de Tuberculosi Experimental, Servei de Microbiologia, Fundació Institut per a la Investigació en Ciències de la Salut Germans Trias i Pujol, Badalona, Barcelona, Spain
b Universitat Autònoma de Barcelona, Barcelona, Spain
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This article reviews the pathophysiology of the latent form of Mycobacterium tuberculosis along with its natural history and progression in infected tissues. The proposed hypotheses regarding the relationship between M tuberculosis and the associated immune response, the cause of granuloma necrosis, the tolerance of a certain concentration of the bacillus in host tissues, the constant turnover of cells in the lung, and the effect of chemotherapy form the basis for the design of the therapeutic vaccine RUTI against latent M tuberculosis infection. This vaccine is generated from detoxified M tuberculosis cell fragments that facilitate a balanced T helper (Th) 1/Th2/Th3 response to a wide range of antigens along with intense antibody production. Treatment with RUTI following chemotherapy has been demonstrated to be effective in experimental models in mice and guinea pigs and does not exhibit toxicity.

Key words:
Latent bacilli
Immunotherapy
Mycobacterium tuberculosis
Koch phenomenon
Foamy macrophages
Experimental models
Tolerance
Chemotherapy
Th1/Th2

En este artículo se revisan la fisiopatología de la forma la-tente de Mycobacterium tuberculosis, su naturaleza y su evo-lución en los tejidos infectados. Las hipótesis planteadas en-tre la relación de este bacilo con la respuesta inmunitaria generada, el origen de la necrosis intragranulomatosa, la to-lerancia hacia cierta concentración bacilar en los tejidos del hospedador, el constante recambio celular en los pulmona-res y el efecto inducido por el tratamiento quimioterápico permiten conocer las bases para el diseño de la vacuna terapéutica RUTI contra la infección latente por M. tuberculosis. Se trata de una vacuna generada a partir de fragmentos ce-lulares de M. tuberculosis biotransformados que permiten generar una respuesta equilibrada de tipo Th1/Th2/Th3 ante un amplio abanico de antígenos, además de una intensa producción de anticuerpos. El tratamiento con RUTI, posterior a la quimioterapia, ya ha demostrado su eficacia en mo-delos experimentales en ratones y cobayas, sin generar nin-guna respuesta tóxica.

Palabras clave:
Bacilos latentes
Inmunoterapia
Mycobacterium tuberculosis
Fenómeno de Koch
Macrófagos foamy
Modelos experimentales
Tolerancia
Quimioterapia
Th1/Th2
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This work was supported by grants FIS 01/0644 and 01/3104 from the Spanish Ministry of Health, and by a grant from the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR) 2003.

Copyright © 2006. Sociedad Española de Neumología y Cirugía Torácica (SEPAR)
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