Biodegradable pulsatile release technologies for viral vector based vaccinations

Vaccines are arguably the greatest public health intervention of modern era medicine. Most vaccines, in order to be effective require multiple doses. This is disadvantageous as there is an increasing trend towards non-compliance with subsequent doses. Viral vectored vaccines represent arguably the next generation of vaccines but they too often require a heterologous prime-boost approach such as the use of Adenoviral-MVA vectors. This thesis describes work utilising biodegradable microparticulate and non-microparticulate technologies to attempt to transform vaccination regimes from multiple into one single injection. Both technologies were tested using the heterologous Adenoviral-MVA prime-boost regime. A novel and virus-tailored encapsulation using the solvent triacetin and qPCR-based quantification methodology is proposed for the microencapsulation of MVA virus in biodegradable PLGA or PLA microparticles. Immunogenicity studies comparing routine prime-boost using 2 injections compared to single-dose administration of soluble Adenovirus with encapsulated MVA virus in PLA microparticles, showed comparable immune responses after 8 weeks. However true pulsatile release kinetic based on T-cell and antibody response kinetics was not observed. When experimentally tested with malarial sporozoite challenge the same formulation failed to provide comparable protective immune responses with a single immunisation after 5 weeks. Further work is still required to manufacture more uniform and reproducible formulations. This work is a significant improvement in the field of viral vector encapsulation in solid polymeric matrices, which could benefit not only human vaccination but also veterinary, including fish vaccination, improving quality of life, reducing public health costs and ultimately saving more lives.