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Design Variation of a Dual-Antigen Liposomal Vaccine Carrier System.

ABSTRACT: The enclosed work focuses on the construction variables associated with a dual-antigen liposomal carrier, delivering encapsulated polysaccharides and surface-localized proteins, which served as a vaccine delivery device effective against pneumococcal disease. Here, the goal was to better characterize and compare the carrier across a range of formulation steps and assessment metrics. Specifically, the vaccine carrier was subjected to new methods of liposomal formation, including alterations to the base components used for subsequent macromolecule encapsulation and surface attachment, with characterization spanning polysaccharide encapsulation, liposomal size and charge, and surface protein localization. Results demonstrate variations across the liposomal constructs comprised two means of surface-localizing proteins (either via metal or biological affinity). In general, final liposomal constructs demonstrated a size and zeta potential range of approximately 50 to 600 nm and -4 to -41 mV, respectively, while demonstrating at least 60% polysaccharide encapsulation efficiency and 60% protein surface localization for top-performing liposomal carrier constructs. The results, thus, indicate that multiple formulations could serve in support of vaccination studies, and that the selection of a suitable final delivery system would be dictated by preferences or requirements linked to target antigens and/or regulatory demands.

SUBMITTER: Nayerhoda R

PROVIDER: S-EPMC6747791 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Design Variation of a Dual-Antigen Liposomal Vaccine Carrier System.

Nayerhoda Roozbeh R Hill Andrew A Beitelshees Marie M Jones Charles C Pfeifer Blaine B

Materials (Basel, Switzerland) 20190901 17

The enclosed work focuses on the construction variables associated with a dual-antigen liposomal carrier, delivering encapsulated polysaccharides and surface-localized proteins, which served as a vaccine delivery device effective against pneumococcal disease. Here, the goal was to better characterize and compare the carrier across a range of formulation steps and assessment metrics. Specifically, the vaccine carrier was subjected to new methods of liposomal formation, including alterations to th ...[more]

PMID: 31480544

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Project description:BackgroundAdjuvant formulations are critical components of modern vaccines based on recombinant proteins, which are often poorly immunogenic without additional immune stimulants. Oil-in-water emulsions comprise an advanced class of vaccine adjuvants that are components of approved seasonal and pandemic influenza vaccines. However, few reports have been published that systematically evaluate the in vitro stability and in vivo adjuvant effects of different emulsion components.ObjectivesTo evaluate distinct classes of surfactants, oils, and excipients, for their effects on emulsion particle size stability, antigen structural interactions, and in vivo activity when formulated with a recombinant H5N1 antigen.MethodsEmulsions were manufactured by high pressure homogenization and characterized alone or in the presence of vaccine antigen by dynamic light scattering, zeta potential, viscosity, pH, hemolytic activity, electron microscopy, fluorescence spectroscopy, and SDS-PAGE. In vivo vaccine activity in the murine model was characterized by measuring antibody titers, antibody-secreting plasma cells, hemagglutination inhibition titers, and cytokine production.ResultsWe demonstrate that surfactant class and presence of additional excipients are not critical for biological activity, whereas oil structure is crucial. Moreover, we report that simplified two-component emulsions appear more stable by particle size than more complex formulations.Finally, differences in antigen structural interactions with the various emulsions do not appear to correlate with in vivo activity.ConclusionsOil-in-water emulsions can significantly enhance antibody and cellular immune responses to a pandemic influenza antigen. The dramatic differences in adjuvant activity between squalene-based emulsion and medium chain triglyceride-based emulsion are due principally to the biological activity of the oil composition rather than physical interactions of the antigen with the emulsion.

Dataset Information

Design Variation of a Dual-Antigen Liposomal Vaccine Carrier System.

Publications

Design Variation of a Dual-Antigen Liposomal Vaccine Carrier System.

Similar Datasets

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