New strategies in vaccine design for the induction of CD8 T cell responses using biodegradable iron oxide nanoparticles

Abstract

Abstract For vaccines targeting diseases such as malaria and cancer, CD8 T cell responses are vital. Traditional adjuvants, like alum, are incapable of inducing these responses and thus new delivery strategies are required. Previously, we have shown that biocompatible polystyrene nanoparticles (PSNPs) (carboxylate, 40–50 nm) can induce potent cytotoxic T cell and antibody responses when conjugated to antigen and can protect mice against experimental tumours or clear large established tumours after a single immunization. As a biodegradable alternative; we synthesised ~50 nm iron oxide nanoparticles (IONPs) stabilized with the polysaccharide pullulan. The IONPs share similar characteristics (size, charge and shape) with the PSNPs, are stable, non-toxic, rapidly taken up by dendritic cells in vitro and are considered inert as they do not upregulate costimulatory markers. The adjuvant/carrier capabilities of IONPs when conjugated to model antigen ovalbumin (OVA) were assessed in vivo. IONPs can induce strong antibody responses but failed to boost the T cell response (Th1 and Th2) after two immunisations, despite their similarity to PSNPs. This implies that the composition of a NP can affect its interactions with the immune system and as such its behaviour as a carrier. To produce an IONP delivery system in which CD8 T cells could also be induced in addition to strong antibody responses, IONPs were co-delivered with the TLR9 agonist CpG. This led to > 2-fold increases in CD8 T cell and antibody responses above either IONPs or CpG alone. Therefore, these biodegradable particles have the capacity to synergize with an inflammatory adjuvant and provide a new strategy for vaccine delivery focused on the induction of CD8 T cell responses.