Magnetic Nanovectors for the Development of DNA Blood-Stage Malaria Vaccines.
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 encodingPlasmodium 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.
Department of Chemical Engineering, Monash University, 18 Alliance Lane, Clayton, VIC 3800, Australia. fatin.mn70@gmail.com.
Fatin M Nawwab
FM
Al-Deen
Department of Immunology and Pathology, Central Clinical School, Faculty of Medicine, Nursing and Health Sciences, Monash University, 89 Commercial Road, Melbourne, VIC 3004, Australia. sue.xiang@monash.edu.
Sue D
SD
Xiang
Department of Microbiology, Monash University, Wellington Road, Clayton, VIC 3800, Australia. charles.ma@monash.edu.
Charles
C
Ma
Department of Immunology and Pathology, Central Clinical School, Faculty of Medicine, Nursing and Health Sciences, Monash University, 89 Commercial Road, Melbourne, VIC 3004, Australia. kirsty.wilson@monash.edu.
Kirsty
K
Wilson
Department of Microbiology, Monash University, Wellington Road, Clayton, VIC 3800, Australia. ross.coppel@monash.edu.
Ross L
RL
Coppel
Department of Chemical Engineering, Monash University, 18 Alliance Lane, Clayton, VIC 3800, Australia. Cordelia.selomulya@monash.edu.
Cordelia
C
Selomulya
Department of Immunology and Pathology, Central Clinical School, Faculty of Medicine, Nursing and Health Sciences, Monash University, 89 Commercial Road, Melbourne, VIC 3004, Australia. Magdalena.plebanski@monash.edu.
Magdalena
M
Plebanski
MSP119; antibody; hyaluronic acid; immune response; magnetic gene vector; malaria DNA vaccine; superparamagnetic iron oxide nanoparticles (SPIONs)