TY - JOUR
T1 - Magnetic nanovectors for the development of DNA blood-stage malaria vaccines
AU - Nawwab Al-Deen, Fatin M.
AU - Xiang, Sue D.
AU - Ma, Charles
AU - Wilson, Kirsty
AU - Coppel, Ross
AU - Selomulya, Cordelia
AU - Plebanski, Magdalena
PY - 2017/2/10
Y1 - 2017/2/10
N2 - 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.
AB - 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.
KW - Hyaluronic acid
KW - MSP119
KW - Superparamagnetic iron oxide nanoparticles (SPIONs)
KW - Magnetic gene vector
KW - Malaria DNA vaccine
KW - Antibody
KW - Immune response
UR - http://www.scopus.com/inward/record.url?scp=85012969716&partnerID=8YFLogxK
U2 - 10.3390/nano7020030
DO - 10.3390/nano7020030
M3 - Article
AN - SCOPUS:85012969716
VL - 7
JO - Nanomaterials
JF - Nanomaterials
SN - 2079-4991
IS - 2
M1 - 30
ER -