Abstract
Vaccines against blood-stage malaria often aim to induce antibodies to neutralize parasite entry into red blood cells, interferon gamma (IFNγ) produced by T helper 1 (Th1) CD4+ T cells or interleukin 4 (IL-4) produced by T helper 2 (Th2) cells to provide B cell help. One vaccine delivery method for suitable putative malaria protein antigens is the use of nanoparticles as vaccine carriers. It has been previously shown that antigen conjugated to inorganic nanoparticles in the viral-particle size range (~40–60 nm) can induce protective antibodies and T cells against malaria antigens in a rodent malaria challenge model. Herein, it is shown that biodegradable pullulan-coated iron oxide nanoparticles (pIONPs) can be synthesized in this same size range. The pIONPs are non-toxic and do not induce conventional pro-inflammatory cytokines in vitro and in vivo. We show that murine blood-stage antigen MSP4/5 from Plasmodium yoelii could be chemically conjugated to pIONPs and the use of these conjugates as immunogens led to the induction of both specific antibodies and IFNγ CD4+ T cells reactive to MSP4/5 in mice, comparable to responses to MSP4/5 mixed with classical adjuvants (e.g., CpG or Alum) that preferentially induce Th1 or Th2 cells individually. These results suggest that biodegradable pIONPs warrant further exploration as carriers for developing blood-stage malaria vaccines.
Highlights
Vaccines against distinct stages of the malaria life cycle have different requirements with respect to the immune responses they need to induce
Synthesis of Pullulan-Coated Iron Oxide Nanoparticles pullulan-coated iron oxide nanoparticles (pIONPs) were synthesized by precipitating ferric chloride and ferrous sulphate in the presence of a large excess of unmodified pullulan
1 g of pullulan was dissolved in 20 mL water and combined with 0.159 g ferric chloride and 0.079 g ferrous sulphate dissolved in 10 mL water
Summary
Vaccines against distinct stages of the malaria life cycle have different requirements with respect to the immune responses they need to induce. Vaccine-induced immunity against merozoites (blood-stage malaria parasites) will likely need to mimic naturally acquired immunity, controlling the extent of infection rather than preventing it [1]. Antibodies are the key in such a response, acting to prevent merozoite growth and replication, primarily by inhibiting cell invasion [2]. Recent studies show antibodies can activate the classical complement pathway and opsonize merozoites for phagocytosis or killing by monocytes, macrophages and neutrophils [3,4,5]. Vaccines 2020, 8, 651 blood-stage protection in rodent malaria models [6]. Their importance in human malaria infection remains unclear
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