Advances in Single-Shot Vaccine Development - Biodegradable microsphere-based systems may eliminate the need for booster shots. - BioPharm International

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Advances in Single-Shot Vaccine Development
Biodegradable microsphere-based systems may eliminate the need for booster shots.


BioPharm International Supplements


Delayed Antigen Release from Dex-HEMA Microspheres

Once the freeze-dried microsphere product is rehydrated by reconstitution in an aqueous solution, hydrolysis of the carbonate ester groups in the dex-HEMA will be initiated. This will increase the mesh size in the hydrogel network. The encapsulated protein will be released when the mesh size exceeds the hydrodynamic diameter of the protein. The actual release profile of the encapsulated protein is primarily determined by the matrix density.


Figure 6. The effect of dex-HEMA DS and initial water content on in vitro release of IgG. In vitro release of proteins is measured in time during incubation at physiological conditions. Release is expressed as percent of the maximal released amount of protein.
It has been shown that the release of proteins and liposomes can be tailored from days to months by varying the main factors influencing the matrix density, which are the relative number of HEMA groups in dex-HEMA (degree of substitution, DS) and the initial water content of the microspheres.2,4,7,8 In Figure 6, the effects of different DS and initial water content on in vitro release profiles of a model protein, IgG, are presented.


Figure 7. Antibody titers induced by HBsAg administered as a protein solution, admixed with placebo microspheres (MSP), or encapsulated in OctoVAX microspheres (MSP). Antibody titers at day 84 are represented as geometric mean titers per group of 10 animals in relation to an international reference standard.
Most other microsphere delivery technologies, such as the poly-lactic-co-glycolic acid (PLGA)–based delivery technology, comprise process steps that expose the protein to potentially detrimental organic solvents. In contrast, the OctoVAX microsphere formulation is a completely aqueous process, which limits the effects of manufacturing on the integrity of the encapsulated proteins. Furthermore, because of the open matrix of the microspheres, hydrolytic degradation does not induce local acidification that may affect the protein's activity. As part of our single-shot vaccine development program, we have recently shown in a mouse model that the potency to induce an antibody response is comparable between encapsulated HBsAg and freely injected HBsAg (Figure 7). These data suggest that the HBsAg particle domains that induce these antibody responses are not affected by the formulation process or by the release process.


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