Engineered Polylactic Acid (PLA) Microcapsules for Spatiotemporally Coupled Delivery and Synergistically Enhanced...

Area of Science:

• Vaccinology
• Materials Science
• Immunology

Background:

• Microcapsules are researched as particulate adjuvants in vaccine development.
• Designing effective microcapsule-based composite adjuvant systems remains challenging.

Purpose of the Study:

• To develop polylactic acid (PLA) microcapsules with combined delivery and immunopotentiator properties.
• To evaluate the humoral and cellular immune responses elicited by these microcapsule formulations in mice.

Main Methods:

• Preparation of uniform polylactic acid (PLA) microcapsules (MC) and monophosphoryl lipid A (MPLA) composite microcapsules (MPLA@MC).
• Formulation of ovalbumin (OVA) loaded microcapsules (OVA@MC) and composite microcapsules (OVA&MPLA@MC).
• Assessment of cellular uptake, lysosomal escape, in vivo humoral and cellular immune responses, and immune pathway activation via RNA sequencing.

Main Results:

• Microcapsule formulations promoted cellular uptake and lysosomal escape.
• OVA&MPLA@MC significantly enhanced IgG antibody levels and induced Th1-biased responses.
• Strong cellular immunity was observed, with increased Interferon-γ (IFN-γ) and Granzyme B (Gzmb) secretion, enhanced phagocytosis, and activated immune signaling pathways.

Conclusions:

• A rationally designed composite microcapsule strategy offers a potent platform for synergistic immune responses.
• This approach opens new avenues for developing effective therapeutic and anti-infectious vaccines.