Malaysian Journal of Medical Sciences School of Medical Sciences, Universiti Sains Malaysia ISSN: 1394-195X Vol. 17, Num. 2, 2010, pp. 66-67

Malaysian Journal of Medical Sciences, Vol. 17, No. 2, 2010, pp. 66-67

Letter to the Editor

Antibody mediated immunity — a missed opportunity in the fight against tuberculosis?

Armando ACOSTA¹, Mohd Nor NORAZMI², Maria Elena SARMIENTO¹

¹Instituto Finlay Ciudad Habana, Cuba
²School of Health Sciences, Universiti Sains Malaysia Health Campus, 16150 Kubang Kerian, Malaysia

Correspondence: Prof. Dr Armando Acosta, MD, PhD (Instituto Finlay), Calle 17 esquina 198, Rpto. Siboney, Playa, Ciudad de la Habana, Cuba, Tel: +53(7) 271-6911 ext. 106 Fax: +53(7) 208-6075 E-mail: aracosta2005@yahoo.es

Code Number: mj10024

Dear Editor,

Tuberculosis is one of the leading causes of mortality produced by a single infectious agent. Each year 8 million new cases and between 2 to 3 million deaths are reported. One-third of the human population is already infected with Mycobacterium tuberculosis—the causative agent of tuberculosis. The disease is increasing at a worrying rate primarily due to the absence of an effective vaccine, the emergence of multi-drug resistant strains, as well as co-infection with HIV; coupled with the low diagnostic and therapeutic coverage in many developing countries.

The role of cell-mediated immunity against mycobacteria, and in particular, M. tuberculosis has been fully established. Up to now all the efforts for the development of new or improved vaccines against tuberculosis have been directed toward the induction of an effective cell-mediated immune response. However, the potential role of antibodies for protection against M. tuberculosis infection have been underestimated on the assumption that they have limited effect, if any, against intracellular pathogens.

M. tuberculosis gains access to the host through the mucosa of lung alveoli, thus the presence of specific antibodies in mucosal secretions could inhibit bacterial colonization. In fact, our group has demonstrated the protective capacity of secretory IgA monoclonal antibodies directed against M. tuberculosis antigens as well as formulations of human gammaglobulins against models of infection with BCG and M. tuberculosis in mice (1,2,3). Similar results have been obtained with human secretory IgA in the same animal model (unpublished observations). Using different animal models and antibody formulations, other groups have reported the protective role of antibodies in M. tuberculosis infection (4).

Potential mechanisms by which antibodies could modify the outcome of mycobacterial infection could be mediated by interference with adhesion, toxin neutralization, opsonization, activation of complement, increase in cytokine expression, enhancement of phagosome-lysosome fusion, and enhancement of antigen presentation among others (5).

Future applications of antibody formulations for the control of tuberculosis may include: treatment of patients infected with multidrug resistant strains, combination with the standard treatment in order to achieve shorter therapeutic regimes, and administration to recent contacts of tuberculosis patients and risk groups. Since BCG, the current vaccine against tuberculosis is only protective in the severe forms of the infection in childhood and is not protective against the pulmonary disease in adults — the most common form of the disease. Hence the development of new tuberculosis vaccines is urgently required (6).

The induction of specific antibody responses by vaccination in addition to the stimulation of cell-mediated immunity could be a novel strategy for the development of new generation prophylactic and therapeutic vaccines against tuberculosis. Taking into consideration this possibility, our group has been working on recombinant BCG strains expressing T and B epitopes of M. tuberculosis, with some encouraging results with respect to immunogenicity and protection in mice (unpublished results).

Accumulated reports in favour of the protective role of specific antibodies in tuberculosis provide us with potential improvements in prophylactic, therapeutic, and diagnostic methods to enhance future control measures against the disease.

Acknowledgements

Some of the results presented were kindly supported by MOSTI Grant No: 07-01-05-MEB007.

References

1. Olivares N, Leon A, Lopez Y, Puig A, Cadiz A, Falero G, et al. The effect of the administration of human gamma globulins in a model of BCG infection in mice. Tuberculosis. 2006;86(3-4):268–272.
2. Olivares N, Puig A, Aguilar D, Moya A, Cadiz A, Otero O, et al. Prophylactic effect of administration of human gamma globulins in a mouse model of tuberculosis. Tuberculosis. 2009;89(3):218–220.
3. López Y, Yero D, Falero-Diaz G, Olivares N, Sarmiento ME, Sifontes S, et al. Induction of a protective response with an IgA monoclonal antibody against Mycobacterium tuberculosis 16kDa protein in a model of progressive pulmonary infection. Int J Med Microbiol. 2009;299(6):447–452.
4. Abebe F, Bjune G. The protective role of antibody responses during Mycobacterium tuberculosis infection. Clin Exp Immunol. 2009;157:235–243.
5. Glatman-Freedman A, Casadevall A. serum therapy for tuberculosis revisited: reappraisal of the role of antibody-mediated immunity against Mycobacterium tuberculosis. Clin Microbiol Rev. 1998;11(3):514–532.
6. Norazmi MN, Sarmiento ME, Acosta A. Recent Advances in Tuberculosis Vaccine Development. Curr Resp Med Rev. 2005,1(2):109–116.

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