**6. Potential uses of antibodies against TB**

Future applications of antibody formulations for the control of TB may include several possibilities including treatment, prevention and diagnosis.

#### **6.1. Treatment**

Antibody based therapy could potentially be useful in several scenarios. They could be used to shorten the standard treatment period of patients with uncomplicated TB when coupled with standard chemotherapy. However, they would be particularly important in the treatment of patients infected with Multidrug Resistant (MDR) and Extensively Drug Resistant (XDR) strains, in combination with the standard treatment.

### **6.2. Prophylactic use**

Prophylactic use of antibodies could be applied in recent contacts of TB patients, with special attention to risk groups [84]. In this regard, successful prophylactic use of antibodies in exposed individuals has been shown in the case of several other pathogens such as varicella, tetanus, Respiratory Synsicial Virus (RSV), rabies and Hepatitis B [85, 86]

B and T epitopes which are potentially cross reactive with those of *M. tuberculosis*. It is important to note that there could be conformational B epitopes and additional epitopes related with lipids and carbohydrates included in the proteoliposomes that could reinforce the

The Role of Antibodies in the Defense Against Tuberculosis

http://dx.doi.org/10.5772/53950

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Considering the results of the *in silico* analysis, proteoliposomes of *M. smegmatis* were obtained and their immunogenicity was studied in mice [93]. In addition to cellular immune effectors recognizing antigens from *M. tuberculosis*, cross reactive humoral immune responses of several IgG subclasses corresponding with a combined Th1 and Th2 pattern against antigenic components of *M. tuberculosis* were elicited. These findings were in concordance with the *in silico* predictions [93, 94]. It is interesting to note that differences in the pattern of humoral recognition of lipidic components was dependent on the characteristics of the adjuvant used, which could have relevance for the development of vaccines which includes lipidic compo‐ nents [93]. Currently studies are underway to evaluate the protective capacity of *M. smegma‐*

Bioinformatics tools for prediction of T and B epitopes were also employed for the design of multiepitopic constructions, which were used to obtain recombinant BCG strains. Based on this prediction, B cell epitopes from ESAT-6, CFP-10, Ag87B and MTP40 proteins were selected and combined with T cell epitopes of the 87B protein and fused to Mtb8.4 protein [96].

A significant IgG antibody response against specific B cell epitopes of ESAT-6 and CFP-10 was obtained in mice immunized with the recombinant strain. After studying the specific response of spleen cells by lymphoproliferation assay and detection of intracellular cytokines in CD4 + and CD8 + subpopulations, the recognition of T epitopes was also observed. The response showed a Th1 pattern after immunization with this recombinant strain (Mohamud, R, et al. manuscript in preparation). In another series of experiments, recombinant BCG strains expressing several combinations of multiepitopic constructions were used to immunize BALB/ c mice subcutaneously and challenged intratracheally with the *M. tuberculosis* H37Rv strain. Recombinant BCG strains expressing T epitopes from 87BAg fused to Mtb8.4 protein and BCG expressing a HSP62 T cell epitope plus different combinations of B cell epitopes from 87BAg, Mce1A, L7/L12, 16 kDa, HBHA, ESAT6, CFP10 and MTP40 and combinations of B cell epitopes alone produced significant reductions in lung CFU compared to BCG (Norazmi MN, et al.

Although no serological assays are currently recommended for diagnosis of TB [97], largely due to the possibility of false results and thus incorrect treatments, for many other pathogens, serological diagnostic tests has been of great value, particularly in poor countries. In some cases, antibody responses can constitute useful correlates of protection [98]. In the specific case of TB, several studies of the antibody response have been reported [99]. There is a substantial amount of variability in antibody response to TB [100]. This variability has been attributed to several factors. Some of these factors are associated with the pathogen (strain variation, microenvironment and growth state of bacteria) and others are related to the host, primarily previous

*tis* proteoliposomes in challenge models with *M. tuberculosis* in mice.

humoral cross reactivity.

manuscript in preparation).

exposure to related antigens and host genetics [99].

*6.3.3. Diagnosis*
