Abstract
(STEVE COLE/GETTY IMAGES)
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To provide effective patient protection, many traditional vaccines require multiple injections, which results in a costly
and inconvenient regimen. These disadvantages have spurred the development of single-shot vaccines that can provide protection
against infection with only one injection. This article describes the manufacture and early results of a prototype single-shot
vaccine combining a prime and booster dose in one injection. The development process is based on the example of a hepatitis
B vaccine.
Figure 1. Illustration of single-shot (B) versus traditional (A) vaccination schemes
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Vaccines contribute significantly to improving world health by prevent the debilitating, and in some cases, fatal effects
of infectious diseases by inducing a protective immune response against the causative agent. Vaccines' success is limited,
however, by the need for multiple injections, and because this costly and inconvenient regimen often leads to logistical challenges
and poor patient compliance. Recent advances in the use of biodegradable microsphere-based systems show the potential of developing
single-shot vaccines to overcome this limitation. Based on the example of hepatitis B vaccination, this article describes
the development process of a prototype single-shot vaccine combining a prime and booster dose in one injection.
The Single-Shot Vaccine Concept
Table 1. Important determinants for single-shot vaccine development
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The single-shot vaccine is a combination product of a prime component—antigen with an appropriate adjuvant—and a microsphere
component that encapsulates antigen and provides the booster immunizations by delayed release of the antigen (Figure 1). Many
aspects need to be taken into consideration when developing such controlled release technology-based vaccines (Table 1).
The microsphere component uses OctoPlus's proprietary OctoVAX microsphere technology, which is based on cross-linked modified
dextran polymers. Dextrans are ideal polymers to form biocompatible hydrogels. Two major advantages of dextran microspheres
as protein delivery systems are that the particles are prepared in the absence of organic solvents, and that degradation of
the microspheres does not result in a pH drop. Both exposure to organic solvents and an acidic environment are known to negatively
affect protein stability.1 Several different dextrans have been developed for hydrogel formation. One of these dextran-based polymers is derivatized
with hydroxy-ethyl methacrylate (dex-HEMA, Figure 2), which introduces hydrolytically sensitive carbonate ester groups that
ensure biodegradation under physiological conditions.2 Studies have shown that protein therapeutics developed with this polymer retain the activity of the encapsulated protein
following encapsulation and release.3
Figure 2. Chemical structure of dex-HEMA, the building block of the hydrogel microspheres. The carbonate ester site that confers
hydrolytic sensitivity to the dex-HEMA is indicated.
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