Pulmonary dry powder vaccine of pneumococcal antigen loaded nanoparticles

Abstract

Pneumonia, caused by Streptococcus pneumoniae, mainly affects the immunocompromised, the very young and the old, and remains one of the leading causes of death. A steady rise in disease numbers from non-vaccine serotypes necessitates a new vaccine formulation that ideally has better antigen stability and integrity, does not require cold-chain and can be delivered non-invasively. In this study, a dry powder vaccine containing an important antigen of S. pneumoniae, pneumococcal surface protein A (PspA) that has shown cross-reactivity amongst serotypes to be delivered via the pulmonary route has been formulated. The formulation contains the antigen PspA adsorbed onto the surface of polymeric nanoparticles encapsulated in l-leucine microparticles that can be loaded into capsules and delivered via an inhaler. We have successfully synthesized particles of ∼150nm and achieved ∼20μg of PspA adsorption per mg of NPs. In addition, the spray-dried powders displayed a FPF of 74.31±1.32% and MMAD of 1.70±0.03μm suggesting a broncho-alveolar lung deposition facilitating the uptake of the nanoparticles by dendritic cells. Also, the PspA released from the dry powders maintained antigen stability (SDS-PAGE), integrity (Circular dichroism) and activity (lactoferrin binding assay). Moreover, the released antigen also maintained its antigenicity as determined by ELISA.