Abstract:
:Based on their immunodominant nature and ability to induce appropriate immune responses in the host, several antigens of Mycobacterium tuberculosis have shown promise of protection. However, most of the candidate vaccines developed by employing various strategies have afforded protection that is at best comparable with bacillus Calmette-Guérin (BCG) in animal models. Due to the inherent ability of BCG to prime cellular responses in the host, it has become an attractive vehicle for development of a vaccine against intracellular infections. In this study, we have cloned the genes of three immunodominant antigens of M. tuberculosis viz. the ESAT6 (Rv3875), the 19 kDa lipoprotein (Rv3763) and the 38 kDa antigen (Pst homolog) (Rv0934) in pSD5 under the transcriptional control of Trrn, a strong mycobacterial promoter, and expressed them in BCG. The19 kDa antigen and the 38 kDa antigen were expressed at levels that were approximately five and eightfolds higher in the cytosols of recombinant BCG strains rBCG19T and rBCG38T, respectively, as compared with their corresponding levels in M. bovis BCG. Both these antigens were also secreted into the extracellular medium at enhanced levels (19 kDa antigen fourfold and 38 kDa antigen twofold) by rBCG strains in comparison with the wild type BCG. ESAT6 antigen, which is absent in M. bovis BCG, was also expressed at a very high level in the cytosol of the rBCG strain (rBCGE6T). Evaluation of immune responses induced by these three rBCG strains in mice shows a markedly different pattern. The rBCG strain overexpressing the 38 kDa antigen exhibited a predominant T helper 1 (Th1) response with high levels of interferon-gamma (IFN-gamma) production, whereas overexpression of the 19 kDa antigen resulted in completely polarized Th2 responses against the BCG sonicate. The rBCG-expressing ESAT6 antigen induced a mixed Th1/Th2 response. Our observations suggest that the 38 kDa antigen may hold excellent promise in the rBCG approach for the development of a vaccine against tuberculosis.
journal_name
Scand J Immunoljournal_title
Scandinavian journal of immunologyauthors
Rao V,Dhar N,Tyagi AKdoi
10.1046/j.1365-3083.2003.01321.xkeywords:
subject
Has Abstractpub_date
2003-10-01 00:00:00pages
449-61issue
4eissn
0300-9475issn
1365-3083pii
1321journal_volume
58pub_type
杂志文章abstract::Cells of the mononuclear phagocytic system (MPS) were described as playing a decisive role in amyloidogenesis. A relationship between the amyloid enhancing factor (AEF) and MPS cells was suggested and recently AEF activity was attributed to a serine esterase (SE) of leucocytic origin. In the present study, no correlat...
journal_title:Scandinavian journal of immunology
pub_type: 杂志文章
doi:10.1111/j.1365-3083.1991.tb01525.x
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journal_title:Scandinavian journal of immunology
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journal_title:Scandinavian journal of immunology
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doi:10.1111/j.1365-3083.1988.tb02398.x
更新日期:1988-06-01 00:00:00
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journal_title:Scandinavian journal of immunology
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journal_title:Scandinavian journal of immunology
pub_type: 杂志文章
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更新日期:1984-12-01 00:00:00
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journal_title:Scandinavian journal of immunology
pub_type: 杂志文章
doi:10.1111/j.1365-3083.1991.tb03755.x
更新日期:1991-02-01 00:00:00
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journal_title:Scandinavian journal of immunology
pub_type: 杂志文章
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journal_title:Scandinavian journal of immunology
pub_type: 杂志文章
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journal_title:Scandinavian journal of immunology
pub_type: 杂志文章
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journal_title:Scandinavian journal of immunology
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journal_title:Scandinavian journal of immunology
pub_type: 杂志文章
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更新日期:1981-01-01 00:00:00
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journal_title:Scandinavian journal of immunology
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journal_title:Scandinavian journal of immunology
pub_type: 杂志文章
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journal_title:Scandinavian journal of immunology
pub_type: 杂志文章
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journal_title:Scandinavian journal of immunology
pub_type: 杂志文章
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journal_title:Scandinavian journal of immunology
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journal_title:Scandinavian journal of immunology
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