DNA-Loaded Cationic Liposomes Efficiently Function as a Vaccine against Malarial Proteins

Wesley L Fotoran; Rachele Santangelo; Beatriz N M de Miranda; Darrell J Irvine; Gerhard Wunderlich

doi:10.1016/j.omtm.2017.08.004

DNA-Loaded Cationic Liposomes Efficiently Function as a Vaccine against Malarial Proteins

Mol Ther Methods Clin Dev. 2017 Aug 23:7:1-10. doi: 10.1016/j.omtm.2017.08.004. eCollection 2017 Dec 15.

Authors

Wesley L Fotoran¹, Rachele Santangelo¹, Beatriz N M de Miranda², Darrell J Irvine^{3

4

5}, Gerhard Wunderlich¹

Affiliations

¹ Department of Parasitology, Institute for Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes 1374, São Paulo, 05508000, Brazil.
² Institute of Chemistry of São Carlos, University of São Paulo, Av. Trabalhador São-Carlense 400, São Carlos, 13566-590, Brazil.
³ Koch Institute for Integrative Cancer Research and Department of Biomedical Engineering and Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
⁴ Ragon Institute of MGH, MIT and Harvard University, Boston, MA, USA.
⁵ Howard Hughes Medical Institute, Chevy Chase, MD, USA.

Abstract

The delivery of antigens as DNA vaccines is an efficient alternative to induce immune responses against antigens, which are difficult to produce in recombinant form. However, the delivery of naked DNA is ineffective or relies on sophisticated ballistic devices. Here, we show a combination of liposome application and naked DNA vaccine that successfully overcomes these problems. Upon entrapment of plasmids encoding different antigens in cationic particles, transfection efficiencies similar to commercial kits were achieved in in vitro cell cultures. The liposome-based approach provided strong humoral responses against three malarial antigens, namely the Circumsporozoite protein and the C terminus of merozoite surface protein 1 from Plasmodium vivax (titers 10⁴ or 10³-10⁴, respectively) and P. falciparum Rhoptry antigen 5 from Plasmodium falciparum (titers 10³-10⁴). When employed in P. falciparum growth-inhibition assays, antibodies demonstrated consistent reinvasion-blocking activities that were dose dependent. Liposome-formulated DNA vaccines may prove useful when targets cannot be produced as recombinant proteins and when conformation-dependent and highly specific antibodies are mandatory.

Keywords: DNA vaccine; cationic liposomes; malaria.