Imran Saleem
Liverpool John Moores University, UK
Title: Dry powder inhalation of Pneumococcal protein-based nanocarrier vaccine
Biography
Biography: Imran Saleem
Abstract
There is a huge drive in the vaccine research field, pharmaceutical industry and Bill Gates Foundation for effective targeting of dendritic cells (DCs) to enhance the immune response and for needle-free vaccination. The aim of this study was to adsorb pneumococcal protein (PspA), onto poly(glycerol adipate-co-ω-pentadecalactone), PGA-co-PDL, nanoparticles (NPs) to target lung DCs. Further to formulate these NPs into dry powder nanocomposite microparticles (NCMPs) suitable for pulmonary vaccine delivery. NPs were prepared using an emulsion solvent evaporation method and PspA was adsorbed onto the surface of NPs (100: 20 [NP: PspA]). The NPs were spray-dried in an aqueous suspension of leucine (1:1.5) to produce NCMPs and characterised in terms of particle size, loading, cell viability, protein stability (SDS-PAGE), integrity (circular dichroism, CD), antigenicity (ELISA), immunization and aerosolisation studies. The NPs produced were 322.83 ± 4.25 nm in size with PspA loading 19.68 ± 2.74 µg/mg. The NCMPs resulted in a fine particle fraction (FPF%) >75%. The NPs appear to be well tolerated by DCs cell lines ≥90% cell viability) at 19.5µg/mL after 4h exposure. SDS-PAGE, CD (α-helical decreased < 13% vs standard PspA) and the antigenicity (>95%) confirmed that PspA was stable in both formulations after spray-drying. The cfu in BALF of mice challenged with pneumococcal bacteria was signifcantly less compared to PspA alone in the lungs or via subcutaneous injection. The PspA loaded NPs were incorporated into NCMPs having excellent aerosolisation characteristics whilst maintaining protein activity. Hence, it may be feasible to use these carriers for pulmonary vaccine delivery.