Live-attenuated ME49Δcdpk3 strain of Toxoplasma gondii protects against acute and chronic toxoplasmosis
Minmin Wu, Shutong Liu, Ying Chen, Deng Liu, Ran An, Haijian Cai, Jie Wang, Nan Zhou, Obed Cudjoe, Meng Han, Jilong Shen, Lijian Chen, Jian Du
Abstract
Abstract Toxoplasmosis, a common parasitic disease, is caused by Toxoplasma gondii , which infects approximately 30% of the world’s population. This obligate intracellular protozoan causes significant economic losses and poses serious public health challenges worldwide. However, the development of an effective toxoplasmosis vaccine in humans remains a challenge to date. In this study, we observed that the knockout of calcium-dependent protein kinase 3 (CDPK3) in the type II ME49 strain greatly attenuated virulence in mice and significantly reduced cyst formation. Hence, we evaluated the protective immunity of ME49Δ cdpk3 as a live attenuated vaccine against toxoplasmosis. Our results showed that ME49Δ cdpk3 vaccination triggered a strong immune response marked by significantly elevated proinflammatory cytokine levels, such as IFN-γ, IL-12, and TNF-α, and increased the percentage of CD4 + and CD8 + T-lymphocytes. The high level of Toxoplasma -specific IgG was maintained, with mixed IgG1/IgG2a levels. Mice vaccinated with ME49Δ cdpk3 were efficiently protected against the tachyzoites of a variety of wild-type strains, including type I RH, type II ME49, Chinese 1 WH3 and Chinese 1 WH6, as well as the cysts of wild-type strains ME49 and WH6. These data demonstrated that ME49Δ cdpk3 inoculation induced effective cellular and humoral immune responses against acute and chronic Toxoplasma infections with various strains and was a potential candidate to develop a vaccine against toxoplasmosis.