Advances in Single-Shot Vaccine Development

Biodegradable microsphere-based systems may eliminate the need for booster shots.
Jan 02, 2009


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
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
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.