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Poly (lactide-co-glycolide) microspheres in respirable sizes enhance an in vitro T cell response to recombinant Mycobacterium tuberculosis antigen 85B.
- Source :
-
Pharmaceutical research [Pharm Res] 2007 Oct; Vol. 24 (10), pp. 1834-43. Date of Electronic Publication: 2007 Jul 27. - Publication Year :
- 2007
-
Abstract
- Purpose: To investigate the use of poly (lactide-co-glycolide) (PLGA) microparticles in respirable sizes as carriers for Antigen 85B (Ag85B), a secreted protein of Mycobacterium tuberculosis, with the ultimate goal of employing them in pulmonary delivery of tuberculosis vaccine.<br />Materials and Methods: Recombinant Ag85B was expressed from two Escherichia coli strains and encapsulated by spray-drying in PLGA microspheres with/without adjuvants. These microspheres containing rAg85B were assessed for their ability to deliver antigen to macrophages for subsequent processing and presentation to the specific CD4 T-hybridoma cells DB-1. DB-1 cells recognize the Ag85B(97-112) epitope presented in the context of MHC class II and secrete IL-2 as the cytokine marker.<br />Results: Microspheres suitable for aerosol delivery to the lungs (3.4-4.3 microm median diameter) and targeting alveolar macrophages were manufactured. THP-1 macrophage-like cells exposed with PLGA-rAg85B microspheres induced the DB-1 cells to produce IL-2 at a level that was two orders of magnitude larger than the response elicited by soluble rAg85B. This formulation demonstrated extended epitope presentation.<br />Conclusions: PLGA microspheres in respirable sizes were effective in delivering rAg85B in an immunologically relevant manner to macrophages. These results are a foundation for further investigation into the potential use of PLGA particles for delivery of vaccines to prevent M. tuberculosis infection.
- Subjects :
- Acyltransferases administration & dosage
Acyltransferases genetics
Administration, Inhalation
Aerosols
Animals
Antigen Presentation
Antigens, Bacterial administration & dosage
Antigens, Bacterial genetics
Bacterial Proteins administration & dosage
Bacterial Proteins genetics
CD4-Positive T-Lymphocytes metabolism
Cell Line
Chemistry, Pharmaceutical
Cloning, Molecular
Delayed-Action Preparations
Drug Compounding
Escherichia coli genetics
Humans
Hybridomas immunology
Interleukin-2 metabolism
Kinetics
Lymphocyte Activation
Macrophages immunology
Particle Size
Recombinant Proteins immunology
Tuberculosis Vaccines administration & dosage
Tuberculosis Vaccines genetics
Acyltransferases immunology
Antigens, Bacterial immunology
Bacterial Proteins immunology
CD4-Positive T-Lymphocytes immunology
Drug Carriers
Immunity, Cellular
Microspheres
Polyglactin 910 chemistry
Tuberculosis Vaccines immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0724-8741
- Volume :
- 24
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Pharmaceutical research
- Publication Type :
- Academic Journal
- Accession number :
- 17657598
- Full Text :
- https://doi.org/10.1007/s11095-007-9302-8