lipid-a and Toxoplasmosis--Animal

To investigate the vaccine potential of both the Toxoplasma GRA2 and GRA6 antigens, the full length recombinant proteins were produced in Escherichia coli, formulated in MPL adjuvant, and used alone and in combination ("mix"), to immunize CBA/J mice. Although high ratios of specific IgG2a/IgG1 were measured against both proteins, only spleen cells from GRA2-immunized mice and mix-immunized mice produced high amounts of both IFN-gamma and IL-2 upon induction with Toxoplasma gondii Excretory-Secretory Antigens. Intra peritoneal challenge with Toxoplasma cysts resulted in significant reduction of brain cysts in GRA2- and in mix-vaccinated mice only. This study shows the protective efficacy of recombinant GRA2 against chronic infection by T. gondii and confirms the utility of MPL adjuvant in enabling a vaccine candidate to induce a protective Th1 immune response.

Topics: Adjuvants, Immunologic; Animals; Antibodies, Protozoan; Antigens, Protozoan; Brain; Cytokines; Disease Models, Animal; Escherichia coli; Humans; Lipid A; Mice; Mice, Inbred CBA; Protozoan Proteins; Protozoan Vaccines; Th1 Cells; Toxoplasma; Toxoplasmosis, Animal; Vaccines, Subunit; Vaccines, Synthetic

Mice were administered nontoxic monophosphoryl lipid A (MPL) or refined standard bacterial endotoxin (RSE) prior to, simultaneously with, or after infection with Toxoplasma gondii. MPL and RSE given before or with the toxoplasma infection induced significant resistance. Administration of toxic RSE, but not nontoxic MPL, after the establishment of toxoplasma infection significantly shortened the survival time of mice.

Topics: Animals; Dose-Response Relationship, Immunologic; Endotoxins; Humans; Immunity, Innate; Injections, Intraperitoneal; Lipid A; Mice; Salmonella; Toxoplasmosis, Animal