Protective immunity in the rat model of congenital toxoplasmosis and the potential of excreted-secreted antigens as vaccine components

Toxoplasma infection is a major cause of severe foetal pathology both in hu mans and in domestic animals, particularly sheep. We have previously report ed the development of an experimental model to study congenital toxoplasmos is in the rat. Here we demonstrate that, as in humans, total protection aga inst congenital toxoplasmosis can be achieved regardless of the strain of T oxoplasma gondii used to infect rats, or when initial and challenge infecti ons were carried out with different strains. Chronic infection is associate d with a highly specific immunity that involves both B-and T-cell responses beginning at day 10 postinfection. The antibody isotype analysis revealed that whereas immunoglobulin (Ig)G2b is the major elicited isotype, no IgG1 antibodies are detected. T cell proliferation was assayed using crude Toxop lasma extracts or excretory-secretory antigens (ESA). The analysis of T cel l supernatants showed the specific secretion of both interleukin-2 and inte rferon-gamma by activated T cells. Immunization of rats before pregnancy wi th either crude Toxoplasma extracts or with ESA elicited a B cell response that included antibodies of the IgG1 isotype and conferred on the newborns high levels of protection. Preliminary experiments of immunization using tw o HPLC-purified ESA, GRA2 and GRAS, conferred, a significant protection alt hough to a lesser extent. This experimental model represents an attractive model for the identification of future vaccine candidates against congenita l to toxoplasmosis.