Biodegradable implants for the biphasic pulsatile delivery of antigens:Toward single-injection vaccines

Most vaccines require a primary (primer) and after a certain period of time, a secondary (booster) administration of the vaccine to optimally protect the vaccinee against the pathogen. Therefore, most vaccines are administered by using a regime that consists of multiple injections. However, such a prime-boost regime presents several logistical and/or financial problems that lead to under-vaccination. To decrease under-vaccination, these problems could be reduced by developing an injectable biodegradable implant with a biphasic pulsatile release profile. Such an implant mimics the prime-boost regime after a single injection by releasing a part of the vaccine immediately after administration (primer), while the remaining part is released after a certain lag time (booster). The aim of Max Beugeling his research was to investigate the suitability of two different types of biodegradable polymer-based prototypes for the biphasic pulsatile delivery of vaccines. The first prototype was based on a physical mixture of the vaccine and a biodegradable polymer. It was found that this concept may be suitable for the biphasic pulsatile delivery of polysaccharide-based vaccines, but not for protein-based vaccines. Therefore, prototypes based on another concept were evaluated. This concept consisted of a core containing the vaccine (booster) surrounded by a layer of biodegradable polymer that was provided with a layer containing the vaccine (primer). The results show that this concept may indeed be suitable for the biphasic pulsatile delivery of protein-based vaccines. However, for a clinically acceptable product, challenges related to the stability of protein-based vaccines within the implant need to be overcome