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Introduction
In the past few years, extensive efforts in the immunotherapy field have led to the development of several therapeutic vaccine strategies [1-3] . Protein vaccines are popular forms of therapeutic vaccines [3,4] which have been tested successfully in (pre-)clinical studies against various immunological diseases [5,6] . The potency of protein vaccines can be significantly amplified via the encapsulation in biodegradable particles. The use of particles facilitates the uptake of the antigen (Ag) by dendritic cells (DC), allows the co-delivery of Ag and Toll-like receptor ligands (TLRL) [7,8] and improves Ag processing, presentation and T cell priming by DC compared to use of soluble Ag. Generally, particulate Ag is better routed into MHC class I cross-presentation pathways and preserved inside intracellular compartments, resulting in sustained and efficient priming of CD8+ T cell responses [9-13] . DC have superior capacity to cross-present exogenous Ag in MHC I molecules and are considered the major target for vaccines aimed at activating a robust CD8+ T cell mediated immunity [3,14] .
Most clinical trials for cancer immunotherapy have relied on the use of Montanide, a GMP-grade version of incomplete Freund's adjuvant (IFA), which is a water-in-oil (w/o) emulsion for Ag delivery. The immune-activating properties of Montanide are partially explained through the formation of a local Ag depot and the onset of inflammation, which attracts immune cells toward the site of injection [15] where the Ag is taken up primarily in its soluble form [16] . However, the use of Montanide is associated with significant local adverse effects [5] , reason why there is an urgent need for alternatives [17] .
Nanoparticles (NP) and microparticles (MP) prepared from biodegradable poly(lactic-co-glycolic acid) (PLGA) have been studied extensively for the sustained delivery of proteins and therapeutic agents and as a potential alternative to w/o emulsions [18-20] . Plain PLGA particles have sub-optimal adjuvant properties in vivo resulting in poor DC maturation [9,21] , which can be overcome by the inclusion of TLRL, leading to an efficient induction of TH1-mediated T cell responses with the capacity to control tumors or protect against a viral challenge [7,22-25] .
It is generally assumed that NP, compared to MP, are better for targeted drug delivery due to a better biodistribution [26,27] and ability...