(719h) On Designing Magnetic Nanoparticles for Targeted Delivery of Malaria DNA Vaccine

Malaria is a deadly infectious disease, while to date an effective vaccine still remains elusive. This paper provides an overview of works that we did to develop a gene delivery system for malaria vaccine using magnetic nanoparticles tested under a range of conditions in vitro and in vivo. The examples include the design of magnetic polyplexes stable in physiological conditions with dendritic-cell targeting functionality, and a comparison of efficacy and types of immune responses from plasmid malaria DNA vaccine encoding VR1020-PyMSP1₁₉ delivered via different administration routes in in vivo mouse studies. Higher serum antibody titers against PyMSP1₁₉ were observed with intraperitoneal and intramuscular injections, with robust IgG2a and IgG1 responses observed for intraperitoneal administration, possibly due to the physiology of peritoneum as a major reservoir of macrophages and dendritic cells. Heterologous DNA prime followed by single protein boost vaccination regime also enhanced IgG2a, IgG1, and IgG2b responses, indicating the induction of appropriate memory immunity that can be elicited by protein on recall. These outcomes support the possibility to design superparamagnetic nanoparticle-based DNA vaccines to optimally evoke desired antibody responses, useful for a variety of diseases including malaria.

Related publications:

Al-Deen, F.N., Ma, C., Xiang, S. Selomulya, C.*, Plebanski, M., Coppel, R., 2013, On the efficacy of malaria DNA vaccination with magnetic gene vectors, Journal of Controlled Release, 168:1, 10-17.
Al-Deen, F. N., Selomulya, C.*, Williams, T., 2013, On designing stable magnetic vectors as carriers for malaria DNA vaccine, Colloids and Surfaces B: Biointerfaces, 102, 492– 503.
Al-Deen, F., Ho, J., Selomulya, C.*, Ma, C., Coppel, R., 2011, Superparamagnetic Nanoparticles for Effective Delivery of Malaria DNA Vaccine, Langmuir, 27 (7), pp 3703–3712.

Ho, J., Al-Deen, F., Aboodi, A., Selomulya, C., Xiang, S., Plebanski, M., Forde, G., 2011, N,N’-Carbonyldiimidazole-mediated functionalization of superparamagnetic nanoparticles as vaccine carrier, Colloids and Surfaces B: Biointerfaces, 83, 83-90.
Xiang, S. D., Selomulya, C., Ho, J., Apostolopoulos, V., Plebanski, M., 2010, Delivery of DNA vaccines: an overview on the use of biodegradable polymeric and magnetic nanoparticles, Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology, vol 2, John Wiley & Sons, United States, pp. 205-218.

*: C. Selomulya as the corresponding author