Toward a Single-Dose Vaccination Strategy with Self-Encapsulating PLGA Microspheres

Area of Science:

• Biomaterials Science
• Vaccinology
• Immunology

Background:

• Poly(lactic-co-glycolic acid) (PLGA) microspheres are promising for vaccine delivery due to biocompatibility and controlled antigen release.
• A key challenge is maintaining antigen stability and immunogenicity within PLGA microspheres.

Purpose of the Study:

• To develop and evaluate a novel "self-healing" encapsulation method for protein antigens in PLGA microspheres.
• To assess the immunogenicity and efficacy of these self-encapsulating microspheres as a vaccine platform.

Main Methods:

• Pre-formed PLGA microspheres were loaded with protein antigens under aqueous conditions to minimize antigen degradation.
• Mice were immunized using a prime-boost regimen or a single dose with the self-encapsulating microspheres.
• Immune responses, including antigen-specific CD8α+ T cell and antibody production, were compared to traditional adjuvant formulations.

Main Results:

• Self-encapsulating PLGA microspheres generated significantly enhanced antigen-specific CD8α+ T cell and antibody responses compared to soluble protein with calcium phosphate gel.
• A single dose of microspheres with sustained release (>40 days) achieved immune responses comparable to prime-boost vaccinations.
• The self-healing encapsulation method preserved antigenicity and immunogenicity effectively.

Conclusions:

• Self-encapsulating PLGA microspheres represent a potent vaccine platform with potential for both single-dose and multi-dose vaccination strategies.
• This approach overcomes antigen instability issues, offering a promising alternative to conventional vaccine delivery systems.
• The developed method demonstrates significant potential for improving vaccine efficacy and simplifying administration.