Abstract
DNA vaccines offer cost, flexibility, and stability advantages, but administered alone have limited immunogenicity. Previously, we identified optimal configurations of magnetic vectors comprising superparamagnetic iron oxide nanoparticles (SPIONs), polyethylenimine (PEI), and hyaluronic acid (HA) to deliver malaria DNA encoding Plasmodium yoelii (Py) merozoite surface protein MSP119 (SPIONs/PEI/DNA + HA gene complex) to dendritic cells and transfect them with high efficiency in vitro. Herein, we evaluate their immunogenicity in vivo by administering these potential vaccine complexes into BALB/c mice. The complexes induced antibodies against PyMSP119, with higher responses induced intraperitoneally than intramuscularly, and antibody levels further enhanced by applying an external magnetic field. The predominant IgG subclasses induced were IgG2a followed by IgG1 and IgG2b. The complexes further elicited high levels of interferon gamma (IFN-γ), and moderate levels of interleukin (IL)-4 and IL-17 antigen-specific splenocytes, indicating induction of T helper 1 (Th1), Th2, and Th17 cell mediated immunity. The ability of such DNA/nanoparticle complexes to induce cytophilic antibodies together with broad spectrum cellular immunity may benefit malaria vaccines.
Highlights
DNA vaccines, often described as “third generation” vaccines, offer a new approach for the prevention and therapy of several diseases of both bacterial and viral origin [1,2,3], and have been widely used in laboratory animals and non-human primates to induce protective antibody and cellular immune responses [4]
Further studies on this magnetic gene vector configuration showed that superparamagnetic iron oxide nanoparticles (SPIONs)/PEI/DNA + HA complexes—containing high molecular weight (MW) of hyaluronic acid (900 kDa) and a high HA:PEI charge ratio (100%)—efficiently transfected
The application of an external magnetic field had no impact on the magnitude of such induction on either via i.p. or i.m. routes of injections. These results indicated that plasmid DNA loaded onto magnetic nanoparticles can enhance the expression of CD86 in splenic dendritic cells (DCs) when delivered i.p
Summary
DNA vaccines, often described as “third generation” vaccines, offer a new approach for the prevention and therapy of several diseases of both bacterial and viral origin [1,2,3], and have been widely used in laboratory animals and non-human primates to induce protective antibody and cellular immune responses [4]. DNA vaccines have been shown to be effective in some animals [10], the human clinical potency of DNA vaccines has been disappointing, overall, with no human vaccines licensed to date [11] This is mostly due to the low levels of antigen-specific immune responses induced by naked DNA immunisations. It is expected this problem can be overcome by using delivery systems and devices/carriers which can deliver the DNA effectively across the different biological barriers. This would facilitate the eventual localisation of DNA into intracellular compartments that enhance gene expression in the antigen-presenting cells (APCs) most capable of causing downstream potent antigen-specific immune cell activation [11]
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