Spray-dried pneumococcal membrane vesicles are promising candidates for pulmonary immunization

[Display omitted] Pneumococcal infections represent a global health threat, which requires novel vaccine developments. Extracellular vesicles are secreted from most cells, including prokaryotes, and harbor virulence factors and antigens. Hence, bacterial membrane vesicles (MVs) may induce a protecti...

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Bibliographic Details
Published in:International journal of pharmaceutics 2022-06, Vol.621, p.121794-121794, Article 121794
Main Authors: Mehanny, Mina, Boese, Annette, Bornamehr, Behnoosh, Hoppstädter, Jessica, Presser, Volker, Kiemer, Alexandra K., Lehr, Claus-Michael, Fuhrmann, Gregor
Format: Article
Language:English
Subjects:
Cytokines
Extracellular membrane vesicles
Microparticles
Streptococcus pneumoniae
Uptake
Vaccine
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Summary:[Display omitted] Pneumococcal infections represent a global health threat, which requires novel vaccine developments. Extracellular vesicles are secreted from most cells, including prokaryotes, and harbor virulence factors and antigens. Hence, bacterial membrane vesicles (MVs) may induce a protective immune response. For the first time, we formulate spray-dried gram-positive pneumococcal MVs-loaded vaccine microparticles using lactose/leucine as inert carriers to enhance their stability and delivery for pulmonary immunization. The optimized vaccine microparticles showed a mean particle size of 1–2 µm, corrugated surface, and nanocrystalline nature. Their aerodynamic diameter of 2.34 µm, average percentage emitted dose of 88.8%, and fine powder fraction 79.7%, demonstrated optimal flow properties for deep alveolar delivery using a next-generation impactor. Furthermore, confocal microscopy confirmed the successful encapsulation of pneumococcal MVs within the prepared microparticles. Human macrophage-like THP-1 cells displayed excellent viability, negligible cytotoxicity, and a rapid uptake around 60% of fluorescently labeled MVs after incubation with vaccine microparticles. Moreover, vaccine microparticles increased the release of pro-inflammatory cytokines tumor necrosis factor and interleukin-6 from primary human peripheral blood mononuclear cells. Vaccine microparticles exhibited excellent properties as promising vaccine candidates for pulmonary immunization and are optimal for further animal testing, scale-up and clinical translation.
ISSN:0378-5173
1873-3476
DOI:10.1016/j.ijpharm.2022.121794