Synthetic delivery system for tuberculosis vaccines: immunological evaluation of the M. tuberculosis 38 kDa protein entrapped in biodegradable PLG microparticles

Vordermeier, H. M.; Coombes, Allan G.A.; Jenkins, Paul; McGee, John P.; O’Hagan, Derek T.; Davis, S.S.; Singh, Mahavir

doi:10.1016/0264-410x(95)00084-e

Cited by 76 publications

(29 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…71 kDa-PLG microparticles were prepared by double emulsion solvent evaporation technique (4). The results suggest that PLG microparticles induced higher and prolonged T cell response in comparision to FIA, which were skewed towards TH1 subset, known to impart protection against tuberculosis as demonstrated previously by Vordermeir et at (4).…”

Section: Immune Responses To 71 Kda-plg Microparticlessupporting

confidence: 58%

Protective efficacy of mycobacterial 71 kilodalton cell wall associated protein using poly (DL-lactide-co-glycolide) microparticles as carrier vehicles

Dhiman

Khuller

1997

Indian J Clin Biochem

View full text Add to dashboard Cite

Section: Immune Responses To 71 Kda-plg Microparticlessupporting

confidence: 58%

Protective efficacy of mycobacterial 71 kilodalton cell wall associated protein using poly (DL-lactide-co-glycolide) microparticles as carrier vehicles

Dhiman

Khuller

1997

Indian J Clin Biochem

View full text Add to dashboard Cite

“…Among the polymeric systems developed for pharmaceutical proposals, poly-lactideco-glycolide (PLGA) microspheres have been widely explored in several immuno-logical studies as a controlled delivery system of peptides, native and synthetic proteins and lately, nucleic acids (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27). PLGA microspheres are composed of a sphericalshaped polymeric matrix ranging in diameter from 1 to 250 µm (Figure 1).…”

Section: Poly-lactide-co-glycolide Microspheresmentioning

confidence: 99%

Poly-DL-lactide-co-glycolide microspheres as a controlled release antigen delivery system

Lima

Júnior

1999

Braz J Med Biol Res

View full text Add to dashboard Cite

Successful vaccine application means maximum protection with minimal number of administrations. A rational development of vaccines involves studies of the nature of the antigen as well as of the adjuvant to be used to improve the immune responses. This has provided the impetus for studies to design the degradable devices and for different approaches to antigen delivery by different routes of administration. The development of controlled release systems based on polymeric devices that permit a sustained or pulsed release of encapsulated antigens has attracted much interest. Polymeric delivery systems consist of polymers that release their content continuously in a controlled manner over a period of time. The development of a biocompatible delivery system for parenteral administration offers several advantages in terms of immunoadjuvanticity over other compounds. It was found that, in contrast to other carriers, microspheres are more stable, thus permitting administration by the oral or parenteral route. In the present study, we describe the main characteristics and potentialities of this new immunoadjuvant for oral and parenteral administration. Correspondence

show abstract

“…The selection of antigens for evaluation of their protective efficacy in any approach is based upon the attributes like: (1) predominant recognition by the host, (2) capability to induce both humoral as well as cellular arm of the immune system and (3) induction of a preferred type of immune response, in the context of protection against mycobacterial infections, the Th1 type. By virtue of these properties, several immunodominant antigens of Mycobacterium tuberculosis have been tested as candidate vaccines against TB [2,3]. The most notable ones amongst these have been antigens of the Antigen 85 complex, the 38 kDa antigen, the 19 kDa lipoprotein, the MPT64, the Hsp65 and the ESAT6 [4,5].…”

Section: Introductionmentioning

confidence: 99%

“…The 38 kDa antigen (Rv0934), one of the most extensively studied antigens of M. tuberculosis, has been shown to induce appropriate T-cell responses, very high levels of interferon-g (IFN-g) and significantly increased immunoglobulin G2a (IgG2a) antibody, when delivered entrapped in a PLG polymer, suggesting a shift of the host immune system towards the T helper 1 (Th1) response [3]. In addition, because of its lipoprotein nature, it induces significant levels of interleukin-12 (IL-12) by macrophages in addition to stimulating the CD8 þ cytotoxic T cells necessary for protection against TB [13].…”

Section: Introductionmentioning

confidence: 99%

Modulation of Host Immune Responses by Overexpression of Immunodominant Antigens of Mycobacterium tuberculosis in Bacille Calmette–Guérin

Rao¹,

Dhar²,

Tyagi³

2003

Scand J Immunol

View full text Add to dashboard Cite

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-g (IFN-g) 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.

show abstract

Synthetic delivery system for tuberculosis vaccines: immunological evaluation of the M. tuberculosis 38 kDa protein entrapped in biodegradable PLG microparticles

Cited by 76 publications

References 28 publications

Protective efficacy of mycobacterial 71 kilodalton cell wall associated protein using poly (DL-lactide-co-glycolide) microparticles as carrier vehicles

Protective efficacy of mycobacterial 71 kilodalton cell wall associated protein using poly (DL-lactide-co-glycolide) microparticles as carrier vehicles

Poly-DL-lactide-co-glycolide microspheres as a controlled release antigen delivery system

Modulation of Host Immune Responses by Overexpression of Immunodominant Antigens of Mycobacterium tuberculosis in Bacille Calmette–Guérin

Contact Info

Product

Resources

About