PhD defence R.S. (Renée) van der Kooij

Single-injection prime-boost vaccines based on biodegradable polymers

Many vaccines require multiple doses for optimal protection against the pathogen. Currently, these vaccines are administered by means of multiple injections, which often leads to a lower vaccination coverage. Such a vaccination schedule, also referred to as a prime-boost schedule, consists of the administration of a first dose (primer) followed by a second and sometimes even a third or fourth dose (booster) several weeks, months or years later. Vaccination coverage for the abovementioned vaccines could be improved by developing an alternative vaccine formulation that includes both the primer and the booster doses, so that a single injection is sufficient. The antigen must be released from the formulation in a controlled manner, for example by encapsulating the antigen in a matrix of a biodegradable polymer. In the research of Renée van der Kooij, different formulations were developed with both a pulsatile and a sustained release profile. Two different prototypes of a pulsatile-release implant were found to be suitable for the (biphasic) pulsatile release of a vaccine. However, the prototypes were too large for clinical application, so injectable microspheres were developed. Microspheres with a core-shell structure exhibited a delayed (pulsatile) release of a model antigen, where the lag time could be varied. Monolithic microspheres exhibited a sustained release, where the total release duration could be varied. These microspheres induced a strong antibody response in mice, similar to the immune response after a primer-booster injection of the model antigen. However, further research with a clinically relevant antigen and optimization of the developed formulations and associated release profiles is required.

Promotors: prof.dr. H.W. Frijlink and Dr. W.L.J. Hindrichs