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Clin. Vaccine Immunol. doi:10.1128/CVI.00094-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Induction of a specific strong polyantigenic cellular immune response after short-term chemotherapy controls bacillary reactivation in murine and guinea pig experimental models of tuberculosis

Unitat de Tuberculosi Experimental, Department of Microbiology, Fundació Institut per a la Investigació en Ciències de la Salut Germans Trias i Pujol, Universitat Autònoma de Barcelona, Crta del Canyet s/n, 08916, Badalona, Catalonia, Spain; CIBeRES. Spain; Lionex Diagnostics & Therapeutics GMBH, Braunschweig, Germany

^* To whom correspondence should be addressed. Email: pcardona.igtp.germanstrias{at}gencat.cat.

	Abstract

RUTI is a therapeutic vaccine generated from detoxified and liposomed Mycobacterium tuberculosis (MTB) cell fragments that has demonstrated its efficacy in the control of bacilli reactivation after short-term chemotherapy. The aim of the study was to characterize the cellular immune response generated after the therapeutic administration of RUTI and to corroborate the lack of toxicity of the vaccine. Mice and guinea pig experimental models were infected with a low-dose M.tuberculosis aerosol. RUTI-treated animals showed the lowest bacillary load in the two experimental models used. RUTI also decreased the percentage of pulmonary granulomatous infiltration in the mice and the guinea-pig model. This was not the case after BCG treatment. Cellular immunity was studied through the characterization of the intracellular IFN- producing cells and IFN- secreting cells in splenocytes after stimulation with MTB specific structural and growth-related antigens. Our data show that the difference between the therapeutic administration of BCG and RUTI resides mainly in the stronger activation of IFN-+ CD4+ and CD8+ cells against PPD, ESAT-6 and Ag85B. Both vaccines also triggered a specific immune response against the MTB structural antigens 16 kDa, and 38 kDa, and a marked mRNA expression of IFN-, TNF, IL-12, iNOS and RANTES in the lung. The results show that RUTI therapeutic effect is not only linked to the induction of a Th1 response but to the stimulation of a quicker and stronger specific immunity against structural and growth-related antigens that reduces both the bacillary load and the pulmonary pathology.