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

Area of Science:

• Biomaterials Science
• Vaccinology
• Immunology

Background:

• Tuberculosis (TB) remains a significant global health challenge.
• Effective vaccine delivery to the lungs is crucial for combating Mycobacterium tuberculosis.
• Antigen 85B (Ag85B) is a key secreted protein of M. tuberculosis, making it a target for TB vaccines.

Purpose of the Study:

• To develop and evaluate poly (lactide-co-glycolide) (PLGA) microparticles for pulmonary vaccine delivery.
• To use PLGA microparticles as carriers for Antigen 85B (Ag85B) for tuberculosis (TB) vaccine development.
• To assess the immunogenicity of Ag85B delivered via PLGA microparticles to macrophages.

Main Methods:

• Recombinant Ag85B was produced in E. coli and encapsulated into PLGA microspheres using spray-drying.
• Microspheres were engineered to be respirable in size (3.4-4.3 microm median diameter) for lung delivery.
• The ability of PLGA-Ag85B microspheres to deliver antigen to macrophages and stimulate T-cell response (IL-2 production) was assessed using DB-1 hybridoma cells.

Main Results:

• Manufactured PLGA microspheres were suitable for aerosol delivery and targeted alveolar macrophages.
• PLGA-Ag85B microspheres elicited a significantly higher IL-2 response from DB-1 cells compared to soluble Ag85B.
• The PLGA formulation demonstrated extended epitope presentation, indicating enhanced antigen processing and presentation.

Conclusions:

• PLGA microparticles of respirable size are effective carriers for delivering Ag85B to macrophages in an immunologically relevant manner.
• These findings provide a strong foundation for developing PLGA-based pulmonary vaccines against M. tuberculosis.
• This approach holds potential for preventing tuberculosis infection through enhanced vaccine efficacy.