Prospects for a human Toxoplasma vaccine

Human toxoplasmosis is usually benign, but may occasionally lead to severe or lethal damages when combined with immunosuppressive states or when transmitted to the fetus during pregnancy. Only a vaccine could prevent these harmful effects. The oral route is the natural portal of entry of T. gondii. A protective immune response at the mucosal level is required to kill the parasite as soon as it penetrates the intestinal barrier thus preventing toxoplasma from invading the host and settling into tissues. The probable major roles played by both CD8 T cells and antibodies, specially IgA, suggest that the best strategy would be to stimulate both the cellular and humoral arms of the mucosal immune system. Mucosal dendritic cells have been shown to induce good protection against oral toxoplasma challenge. Our hypothesis is that an acceptable and effective human vaccine would have to carry the optimized synthetic vaccine (subunit, DNA or replicon) plus an appropriate adjuvant and to target the mucosal dendritic cells by means of an inert delivery system such as polymer microparticles, which can be endocytosed by M cells of the gut or nasal-associated lymphoid tissues.