Poly(lactide-co-glycolide) microparticles for the development of single-dose controlled-release vaccines

With the exception of the provision of clean water supplies, vaccination remains the most successful public health intervention strategy for the control of infectious diseases. However, the logistics of delivering at least two to three doses of vaccines to achieve protective immunity are complex and compliance is frequently inadequate, particularly in developing countries. In addition, newly developed purified subunit and synthetic vaccines are often poorly immunogenic and need to be administered with potent vaccine adjuvants. Microparticles prepared from the biodegradable and biocompatible polymers, the poly(lactide-co-glycolides) or (PLG), have been shown to be effective adjuvants for a number of antigens. Moreover, PLG microparticles can control the rate of release of entrapped antigens and therefore, offer potential for the development of single-dose vaccines. To prepare single-dose vaccines, microparticles with different antigen release rates may be combined as a single formulation to mimic the timing of the administration of booster doses of vaccine. If necessary, adjuvants may also be entrapped within the microparticles or, alternatively, they may be co-administered. The major problems which may restrict the development of microparticles as single-dose vaccines include the instability of vaccine antigens during microencapsulation, during storage of the microparticles and during hydration of the microparticles following in vivo administration. In the present review, we discuss the adjuvant effect of PLG microparticles, and also their potential for the development of single-dose vaccines through the use of controlled-release technology.