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Clinical and Vaccine Immunology, August 2008, p. 1229-1237, Vol. 15, No. 8
1071-412X/08/$08.00+0     doi:10.1128/CVI.00094-08
Copyright © 2008, American Society for Microbiology. 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{triangledown}

Evelyn Guirado,1,2 Olga Gil,1,2 Neus Cáceres,1 Mahavir Singh,3 Cristina Vilaplana,1,2 and Pere-Joan Cardona1,2*

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 can Ruti s/n, 08916 Badalona, Catalonia, Spain,1 Ciber Enfermedades Respiratorias, Palma de Mallorca, Spain,2 Lionex Diagnostics and Therapeutics GMBH, Braunschweig, Germany3

Received 17 March 2008/ Returned for modification 7 April 2008/ Accepted 21 May 2008

RUTI is a therapeutic vaccine that is generated from detoxified and liposomed Mycobacterium tuberculosis cell fragments that has demonstrated its efficacy in the control of bacillus reactivation after short-term chemotherapy. The aim of this 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. Mouse and guinea pig experimental models were infected with a low-dose M. tuberculosis aerosol. RUTI-treated animals showed the lowest bacillary load in both experimental models. RUTI also decreased the percentage of pulmonary granulomatous infiltration in the mouse and guinea pig models. This was not the case after Mycobacterium bovis BCG treatment. Cellular immunity was studied through the characterization of the intracellular gamma interferon (IFN-{gamma})-producing cells after the splenocytes' stimulation with M. tuberculosis-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-{gamma}+ CD4+ cells and CD8+ cells against tuberculin purified protein derivative, ESAT-6, and Ag85B that RUTI generates. Both vaccines also triggered a specific immune response against the M. tuberculosis structural antigens Ag16kDa and Ag38kDa and a marked mRNA expression of IFN-{gamma}, tumor necrosis factor, interleukin-12, inducible nitric oxide synthase, and RANTES in the lung. The results show that RUTI's therapeutic effect is linked not only to the induction of a Th1 response but also 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.

* Corresponding author. Mailing address: Unitat de Tuberculosi Experimental, Department of Microbiology, Fundació Institut per a la Investigació en Ciències de la Salut Germans Trias i Pujol, Crta del can Ruti, camí de les escoles s/n, 08916 Badalona, Catalonia, Spain. Phone: 34 93 497 86 86. Fax: 34 93 497 86 54. E-mail: pjcardona.igtp.germanstrias{at}gencat.cat

{triangledown} Published ahead of print on 4 June 2008.

Clinical and Vaccine Immunology, August 2008, p. 1229-1237, Vol. 15, No. 8
1071-412X/08/$08.00+0     doi:10.1128/CVI.00094-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Gil, O., Vilaplana, C., Guirado, E., Diaz, J., Caceres, N., Singh, M., Cardona, P.-J. (2008). Enhanced Gamma Interferon Responses of Mouse Spleen Cells following Immunotherapy for Tuberculosis Relapse. CVI 15: 1742-1744 [Abstract] [Full Text]  


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