الفهرس 
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Abstract
Due to the controversial protective efficacy of the current tuberculosis vaccine, (BCG), intensive efforts are currently devoted to design improved vaccines. Given the high degree of homology shared between Mycobacterium tuberculosis (the causative agent of tuberculosis) and other mycobacteria, we explored the possibility of using proteoliposome (PL) prepared from BCG as an experimental vaccine against tuberculosis with encouraging results in a challenge model in mice.
Proteoliposomes (PLs) derived from BCG containing lipids and cell wall proteins could be potential vaccine candidates against TB. In the present study PLs derived from BCG were extracted and characterized by GCMS, then injected into Balb/c mice to evaluate its immunogenicity. Sera of immunized mice showed high IgG response and a significant increase in IFNγ and IL4. These results showed that PLBCG could be potential vaccine candidates against TB.
Our understanding of the interplay between Mtb and the host innate immune system has extensively expanded in recent years. More in-depth studies are warranted provided knowledge that may help in the identification of either host- or pathogen-directed anti-TB therapeutic targets and contribute to the design of more efficient vaccines. The cost of a new vaccine to be developed within the next 10–15 years would certainly be less than the annual global financial toll of Tb treatment and care. As a result, development of TB vaccine reduces duration and cost of TB therapy. Develop immunotherapy approach could be adopted in vaccine development to reduce the duration of Tb therapy. That’s why we evaluate using IL2 as immunotherapy for TB.
The present study was conducted on 100 Balb/c mice obtained from the animal house in Assiut university. Sixty mice were used to compare the variable immune response against BCG, PLBCG, and PLBCG-AH vaccines. Twenty mice were used to evaluate IL2 as immunotherapy following infection with BCG. The last 20 mice were used as a control for all groups.
In the present study, BCG, PLBCG, and PLBCG-AH have shown to elicit protective responses in mice. This experimental vaccine candidate PLBCG induced higher protection when administered with AH which supports its further evaluation as a tuberculosis vaccine candidate.
Regarding the total IgG response after 42 days from vaccination, it was interesting to note that although both PLBCG and PLBCG-AH showed statistical increases compared to non-immunized mice, the intensity of the response was higher with the use of AH, even superior to the response elicited by BCG.
In our study, the highest concentration of IFN-γ was observed in the PLBCG-AH immunized mice after 4 weeks from starting the experiment. It is interesting to note that IL4 concentrations from both PLBCG and PLBCG-AH groups showed statistical increases compared to non-immunized mice, the intensity of the response was higher with the use of AH, even superior to the response elicited by BCG after 4 weeks from starting the experiment.
Besides investigating the immunogenicity of BCG and PLBCG with and without AH adjuvant, we tried to evaluate IL2 as immunotherapy for T.B.
Treatment with IL2 was evaluated by testing lung homogenate of infected and treated mice through Z.N stain, inoculation on LJ media and, using middle brook agar to determine the growth and bacilli load. Laboratory tests were done for measurement of IgG, INFγ, and IL4 concentrations in serum of infected and infected then treated mice.
The concentrations of IgG, INFγ, and IL4 were compared in infected and in treated mice with IL2. It was noticed that mice treated with IL2 were higher in IgG and, IL4 than BCG. But the INFγ concentration had slightly higher than the normal level. Our results demonstrated that the administration of IL2 could limit the course of mycobacterial infection.
Analysis of the number of bacilli organism in the lung showed a significant reduction for treated mice compared to infected mice with high dose of BCG.