A PLASMID ENCODING MURINE GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR INCREASES PROTECTION CONFERRED BY A MALARIA DNA VACCINE

Using the murine parasite Plasmodium yoelii (Py) as a model for malari a vaccine development, we have previously shown that a DNA plasmid enc oding the Py circumsporozoite protein (PyCSP) can protect mice against sporozoite infection. We now report that mixing a new plasmid PyCSP10 12 with a plasmid encoding murine granulocyte-macrophage colony-stimul ating factor (GM-CSF) increases protection against malaria, and we hav e characterized in detail the increased immune responses due to GM-CSF , PyCSP1012 plasmid alone protected 28% of mice, and protection increa sed to 58% when GM-CSF was added (p < 0.0001). GM-CSF plasmid alone di d not protect, and control plasmid expressing inactive GM-CSP did not enhance protection. GM-CSF plasmid increased Abs to PyCSP of IgG1, IgG 2a, and IgG2b isotypes, but not IgG3 or IgM. IFN-gamma responses of CD 8(+) T cells to the PyCSP 280-288 amino acid epitope increased but CTL activity did not change. The most dramatic changes after adding GM-CS F plasmid were increases in Ag-specific IL-2 production and CD4(+) T c ell proliferation. We hypothesize that GM-CSF may act on dendritic cel ls to enhance presentation of the PyCSP Ag, with enhanced IL-2 product ion and CD4(+) T cell activation driving the increases in Abs and CD8( +) T cell function. Recombinant GM-CSP is already used in humans for m edical purposes, and GM-CSF protein or plasmids may be useful as enhan cers of DNA vaccines.