In summary, the collective results described in this thesis show that nanoparticulate vaccines can be delivered intradermally by coated and hollow microneedles and evoke antigen-specific immune... Show moreIn summary, the collective results described in this thesis show that nanoparticulate vaccines can be delivered intradermally by coated and hollow microneedles and evoke antigen-specific immune responses. The choice of both the nanoparticles and the microneedle(s) could have important influences on the immune responses. Microneedle arrays coated with antigen loaded and lipid bilayer fused mesoporous silica nanoparticles (MSNs) could be a promising system for convenient and fast intradermal delivery of protein antigen, although our results indicate that the system needs to be improved in order to obtain optimal immune responses. Moreover, antigen and adjuvant loaded nanoparticles can increase IgG2a (Th1) and CD8+ responses after intradermal delivery by hollow microneedles. This effect depends on the type and the physicochemical characteristics of the nanoparticles, in which smaller size and controlled release properties of antigen and adjuvant were found to correlate with the stronger effect. Finally, the combination of separate antigen loaded and adjuvant loaded nanoparticles may be as efficient as the antigen and adjuvant co-encapsulated nanoparticles for modification of the immune responses following intradermal immunization. Show less
Synthetic long peptides (SLPs) derived from cancer antigens hold great promise as well-defined antigens for immunotherapy of cancer. However, the formulation of SLPs for in vivo administration... Show moreSynthetic long peptides (SLPs) derived from cancer antigens hold great promise as well-defined antigens for immunotherapy of cancer. However, the formulation of SLPs for in vivo administration still needs to be improved. So far, SLPs have been formulated in Montanide-based water-in-oil emulsions in (pre-)clinical trials. However, the use of Montanide as an adjuvant has some important limitations, such as: non-biodegradability; significant local side effects; poor control of release rate; lack of specific dentritic cell (DC)-activating capacity; and the presence of organic solvents (needed to dissolve the peptides prior to mixing with the adjuvant) in the final formulation. Therefore, alternative formulations containing an effective delivery system for peptide-based cancer vaccines are highly needed. Among the numerous vaccine delivery systems, poly(lactic-co-glycolic acid) (PLGA) biodegradable particulate delivery systems are particularly interesting because they are biocompatible; can protect soluble antigens from degradation and rapid clearance once administered; allow for co-encapsulation of (multiple) antigens and adjuvants; and mimic the size and structure of a pathogen, being more efficiently taken up by DCs than soluble antigen. This thesis describes fundamental studies on the design and applicability in a preclinical setting of PLGA-based particulate formulations for the delivery of SLP-based cancer vaccines. Show less
The best form of protection against influenza is vaccination, in terms of efficacy to protect individuals and reduction of the social impact of epidemics on our human societies. Chapter 1 of this... Show moreThe best form of protection against influenza is vaccination, in terms of efficacy to protect individuals and reduction of the social impact of epidemics on our human societies. Chapter 1 of this thesis details the current influenza vaccines available and their lack of efficacy, and the current need for new adjuvanted influenza formulations. Pathogens are often particles and formulating antigens into nanoparticles (NP) results in systems that resemble the pathogens in terms of size, and notably can promote antigen uptake by dendritic cells (DC). The principal aim of the research in this thesis was to investigate how NP systems can act as an adjuvant for subunit influenza vaccine Show less
