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Poly (lactide-co-glycolide) microspheres in respirable sizes enhance an in vitro T cell response to recombinant Mycobacterium tuberculosis antigen ... - PubMed - NCBI
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Pharm Res. 2007 Oct;24(10):1834-43. Epub 2007 Jul 27.

Poly (lactide-co-glycolide) microspheres in respirable sizes enhance an in vitro T cell response to recombinant Mycobacterium tuberculosis antigen 85B.

Author information

1
Molecular Pharmaceutics, School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7360, USA.

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.

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.

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.

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.

PMID:
17657598
DOI:
10.1007/s11095-007-9302-8
[Indexed for MEDLINE]
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