Protective Effect of a Lipid-Based Preparation fromMycobacterium smegmatisin a Murine Model of Progressive Pulmonary Tuberculosis

Abstract

A more effective vaccine against tuberculosis (TB) is urgently needed. Based on its high genetic homology with Mycobacterium tuberculosis (Mtb), the nonpathogenic mycobacteria, Mycobacterium smegmatis (Ms), could be an attractive source of potential antigens to be included in such a vaccine. We evaluated the capability of lipid-based preparations obtained from Ms to provide a protective response in Balb/c mice after challenge with Mtb H37Rv strain. The intratracheal model of progressive pulmonary TB was used to assess the level of protection in terms of bacterial load as well as the pathological changes in the lungs of immunized Balb/c mice following challenge with Mtb. Mice immunized with the lipid-based preparation from Ms either adjuvanted with Alum (LMs-AL) or nonadjuvanted (LMs) showed significant reductions in bacterial load (P < 0.01) compared to the negative control group (animals immunized with phosphate buffered saline (PBS)). Both lipid formulations showed the same level of protection as Bacille Calmette and Guerin (BCG). Regarding the pathologic changes in the lungs, mice immunized with both lipid formulations showed less pneumonic area when compared with the PBS group (P < 0.01) and showed similar results compared with the BCG group. These findings suggest the potential of LMs as a promising vaccine candidate against TB.

Protective capacity of proteoliposomes fromMycobacterium bovisBCG in a mouse model of tuberculosis

“…17 Lipds are important potential targets for vaccine development against TB considering the importance of these components in the virulence of Mtb. 37,39 Several vaccine candidates containing mycobacterial lipids have demonstrated protective capacity in guinea pigs and mice [40][41][42][43] The current study suggests that PLBCG-Al as a booster to BCG could be a new alternative candidate to be tested for protection against TB in further phases of evaluation.…”

The effect of adjuvants and delivery systems on Th1, Th2, Th17 and Treg cytokine responses in mice immunized with Mycobacterium tuberculosis-specific proteins

“…The immunization with these proteins emulsified with IFA induced the secretion of protective Th1 cytokine (IFN-γ) from spleen cells and also lowered the bacterial load significantly in lungs [40]. Alum salts are known to be Th2-inducing adjuvants, however due to their safety and function of increasing the stability and immunogenicity of recombinant proteins, they have been widely used in pursuit of developing subunit TB vaccines and to compare new adjuvants [41][42][43][44][45]. Despite the positive correlation between the induction of high Th1 responses and protection against TB in mice, it has been shown that the use of Th2 inducing adjuvants, such as Alum, is not associated with harmful effects [46].…”

Induction of Mycobacterium Tuberculosis Lipid-Specific T Cell Responses by Pulmonary Delivery of Mycolic Acid-Loaded Polymeric Micellar Nanocarriers

“…Although total lipid-based liposomes induced CD1 restricted T-cell responses and demonstrated an improved pulmonary pathology ( 39 , 40 ), the specific lipid component among the total lipids that was responsible for the pathological protection was not clear. Recently, a diacylated sulfoglycolipids (Ac 2 SGL) and phosphatidylinositol mannoside 2 (PIM 2 )-loaded liposome vaccine induced protective immune responses in guinea pigs ( 41 ), but the adjuvant effect of PIM 2 and trehalose-6,6-dibehenate (TDB), a component of the liposomal nanocarrier ( 42 , 43 ), may complicate the bacterial and pathological protection observed.…”