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

• Published in: Pharmaceutical research 2007-10, Vol.24 (10), p.1834-1843
• Main Authors: DONGMEI LU, GARCIA-CONTRERAS, Lucila, DING XU, KURTZ, Sherry L, JIAN LIU, BRAUNSTEIN, Miriam, MCMURRAY, David N, HICKEY, Anthony J
• Format: Article
• Language: English
• Subjects: Acyltransferases - administration & dosage; Acyltransferases - genetics; Acyltransferases - immunology; Administration, Inhalation; Aerosols; Animals; Antigen Presentation; Antigens; Antigens, Bacterial - administration & dosage; Antigens, Bacterial - genetics; Antigens, Bacterial - immunology; Bacterial Proteins - administration & dosage; Bacterial Proteins - genetics; Bacterial Proteins - immunology; Biological and medical sciences; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; Cell Line; Chemistry, Pharmaceutical; Cloning, Molecular; Delayed-Action Preparations; Drug Carriers; Drug Compounding; Escherichia coli; Escherichia coli - genetics; General pharmacology; Humans; Hybridomas - immunology; Immunity, Cellular; Interleukin-2 - metabolism; Kinetics; Lymphocyte Activation; Macrophages - immunology; Medical sciences; Microspheres; Mycobacterium tuberculosis; Particle Size; Pharmaceutical technology. Pharmaceutical industry; Pharmacology; Pharmacology. Drug treatments; Polyglactin 910 - chemistry; Recombinant Proteins - immunology; Tuberculosis; Tuberculosis Vaccines - administration & dosage; Tuberculosis Vaccines - genetics; Tuberculosis Vaccines - immunology; Vaccines
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-007-9302-8

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. 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. 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. 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.