Progress Towards the Development of a Vaccine Against Congenital Toxplamosis: Identification of Protective Antigens and the Selection of Appropriate Adjuvants

Abstract

We have recently established that vertical disease transmission from the mother to the foetus, as in humans and sheep, only occurs in BALB/c mice infected with Toxoplasma gondii for first time during pregnancy. Thus a previous infection generally gives life long immunity, as ideally, would an effective vaccine. Of three major fractions harvested from RH strain tachyzoites (membrane, soluble and excretory/secretory) the soluble fraction was found the most effective in reducing mortality and cyst burdens in adult mice. Further studies indicated that the choice of adjuvant could enhance this effect. Entrapment within non-ionic surfactant vesicles (NISV), but not Freund’s Complete Adjuvant, significantly enhanced the protection afforded by soluble antigen to adult mice as well as greatly increasing the T cell specific proliferative response, IFN-γ production and antibody levels. NISV are safe, stable, and inexpensive and promote TH1 and CD8+ lymphocyte activation. In BALB/c dams vaccinated with NISV entrapped soluble antigen and infected on day 12 of pregnancy with 20 tissue cysts of T. gondii (RRA strain), congenital infection was reduced from a control level of 50% to 12% in surviving offspring and foetal death from 50% to nil. The identification of protective antigens in the soluble fraction is well advanced.