Biodegradable polymer microspheres as vaccine adjuvants and delivery systems

Though vaccination has been the most cost-effective way of controlling infectious diseases, the logistics of delivering at least two to three doses of conventional vaccines for primary immunization to achieve protection are difficult and compliance is frequently inadequate, particularly in developing countries. In recent years biodegradable polymer microspheres have received much attention for the purposes of controlled release of antigens, (i) to reduce the number of doses needed for primary immunization to as few as a single dose and (ii) to target an antigen to microfold cells on mucosal surfaces after oral administration or to antigen-presenting cells after parenteral inoculations. A variety of vaccine antigens have been encapsulated in microspheres usually composed of poly (lactic/glycolic) acid (PLGA). Based on the size of the microspheres, molecular weight of polymer and ratio of lactic to glycolic acid in the polymer, the antigen may be targeted to various cells of the immune system or it may form a depot at the site of injection, allowing the slow release of the antigen for extended periods. Additionally, another adjuvant may be incorporated inside microspheres together with the antigen, further enhancing or modulating the immune response to the desired type. The major problems in developing controlled-release vaccines include instability of vaccine antigens during micro-encapsulation, storage and subsequent hydration. We encapsulated tetanus toxoid (TT) and Haemophilus influenzae type b capsular polysaccharide conjugated to TT (Hib-T) inside PLGA microspheres and evaluated the antibody levels in mice. A single injection of these micro-encapsulated vaccines elicited high antibody levels which persisted for several months. The antibody levels were similar or superior to those elicited by conventional formulations of AIPO4-adsorbed TT or soluble Hib-T conjugate vaccine.