Find in Library

Toxoplasmosis caused by <i>Toxoplasma gondii</i> is an important zoonosis of human and animal health significance. Current chemical therapeutics have side effects, and no commercially available vaccine is licensed for the prevention of toxoplasmosis in humans and most animals. Developing a safe and effective vaccine with long-term protection against <i>T. gondii</i> infection is necessary to control toxoplasmosis. HAD2a is a key member of the haloacid dehalogenase (HAD) phosphatase family, which is essential for <i>T. gondii</i> daughter budding. However, the role of HAD2a in <i>T. gondii</i> virulence remains unknown. In this study, we successfully constructed the <i>had2a</i> gene knockout strain in the <i>T. gondii</i>-type I RH strain (RHΔ<i>had2a</i>) and determined its role in virulence and vaccination. These results demonstrate that HAD2a played an important role in parasite daughter budding and in vitro replication. Knockout of the <i>had2a</i> gene attenuated the virulence of the <i>T. gondii</i>-type I RH strain. Vaccination with RHΔ<i>had2a</i> tachyzoites induced a Th1-biased immune response, provided partial protection against acute <i>T. gondii</i> infection in mice by highly virulent tachyzoites of RH and PYS (ToxoDB#9, Chinese I) strains, and conferred strong protection against challenge infection by cysts and oocysts of the less virulent type II Pru strain. These results demonstrate that <i>T. gondii had2a</i> is important for its in vitro proliferation and virulence in mice and that RHΔ<i>had2a</i> may be used as a candidate strain to generate a multiple gene knockout live-attenuated strain or be collaboratively applied with other live-attenuated strains to confer more effective protection against <i>T. gondii</i> infection.