Pulmonary dry powder vaccine of pneumococcal antigen loaded nanoparticles

Area of Science:

• Biotechnology
• Vaccinology
• Nanotechnology

Background:

• Pneumonia, a leading cause of death, is increasingly caused by non-vaccine serotypes of Streptococcus pneumoniae.
• Current vaccines do not fully address the growing threat from these serotypes.
• There is a need for improved vaccine formulations with enhanced stability and non-invasive delivery.

Purpose of the Study:

• To formulate a stable, dry powder inhaler vaccine for Streptococcus pneumoniae using pneumococcal surface protein A (PspA).
• To develop a non-invasive pulmonary delivery system for PspA nanoparticles.
• To assess the stability, integrity, and antigenicity of PspA after formulation and release.

Main Methods:

• Formulation of polymeric nanoparticles (∼150 nm) with adsorbed PspA (∼20 microg/mg NPs).
• Encapsulation of PspA-nanoparticles within L-leucine microparticles for dry powder formulation.
• Characterization of powder properties including fine particle fraction (FPF) and mass median aerodynamic diameter (MMAD).
• Assessment of PspA stability, integrity, and antigenicity using SDS-PAGE, Circular Dichroism, lactoferrin binding assay, and ELISA.

Main Results:

• Successfully synthesized PspA-loaded nanoparticles and encapsulated them into L-leucine microparticles.
• Achieved high PspA adsorption onto nanoparticles and suitable aerodynamic properties (FPF 74.31±1.32%, MMAD 1.70±0.03 µm) for lung deposition.
• Demonstrated that released PspA maintained its stability, integrity, and antigenicity, including binding activity.

Conclusions:

• The developed dry powder formulation provides a promising, stable, and non-invasively delivered PspA vaccine candidate.
• This formulation facilitates pulmonary delivery and uptake by immune cells, potentially enhancing immune response.
• The study supports the development of next-generation pneumococcal vaccines targeting diverse serotypes.