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Received 4 September 2008; received in revised form 9 October 2008; accepted 19 October 2008
Abstract
Mycobacterium tuberculosis is a facultative intracellular pathogen for which cell-mediated immunity is considered
the major component of the immune response. For many decades, the prevailing scientic view has been the antibodies
have little or no role in modifying the course of M. tuberculosis infection. In recent years, several studies
have challenged this dogma, and there is a body of evidence that supports a role of antibodies against M. tuberculosis.
In the present work, we evaluated the protective activity of two monoclonal antibodies (TBA61 and TBA84). Here, we
chose the intratracheal model of pulmonary infection to evaluate bacterial load and morphometric and histological
changes in the lungs of treated mice. Data obtained revealed the reduction of bacterial load and milder morphometric
and histopathological changes in mice treated with TBA61 at 21 days post-infection with M. tuberculosis H37Rv
compared to those treated with TBA84 and control mice. These results allow continuing exploring the potential use of
monoclonal antibodies as prophylactic and therapeutic agents against intracellular pathogens such as M. tuberculosis.
r 2008 Elsevier GmbH. All rights reserved.
Keywords: BCG; Tuberculosis; 38 kDa; 16 kDa; Monoclonal antibody
Introduction
Tuberculosis is an infectious disease caused by
Mycobacterium tuberculosis. It is a pandemic, transmissible, and curable disease. Developing countries are the
most affected by the disease, mainly due to the lack
of resources for diagnostic and treatment. Over two
billions persons worldwide are infected with the bacteria
(Girard et al., 2005). The epidemics have been associated
Corresponding author. Tel.: +53 7 2716911; fax: +53 7 2086075.
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Animals
Pathogen free Balb/c mice were obtained from the
National Institute of Medical Sciences and Nutrition,
Mexico City, Mexico. They were maintained under
barrier conditions in a level III biohazard laboratory.
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Statistical methods
The effects of antibody treatment on the reduction of
bacterial load and in morphometric changes were
analyzed by KruskallWallis test and the distributionfree multiple comparison test. p-Values under 0.05 were
considered statistically signicant. All data analysis was
performed by using the STATISTICA 6.1 Software.
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Fig. 2. Tissue histology sections. Mice were sacriced at 24 h (A, B, and C) and 21 days (D, E, and F) after the challenge with
virulent bacteria, and formalin-xed sections were analyzed. Granulomas became evident at 2 weeks post-infection. Granulomas
were better organized in mice treated with TBA61 (E) compared to those treated with either PBS (D) or TBA84 (F). A, B, and C: HE
100; D, E, and F: HE 40.
Acknowledgements
This investigation was supported by a grant from
UNU-BIOLAC. The studies were also supported by the
Experimental Pathology Section, National Institute of
Medical Sciences and Nutrition, Mexico, where the
experiments were performed.
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