Live-attenuated ME49Δcdpk3 strain of Toxoplasma gondii protects against acute and chronic toxoplasmosis.

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 ME49Δcdpk3 as a live attenuated vaccine against toxoplasmosis. Our results showed that ME49Δcdpk3 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 ME49Δcdpk3 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 ME49Δcdpk3 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.

• Authors: Minmin Wu, Shutong Liu, Ying Chen, Deng Liu, Ran An, Haijian Cai, Jie Wang, Nan Zhou, Cudjoe Obed, Meng Han, Jilong Shen, Lijian Chen, Jian Du
• Journal: NPJ vaccines (NPJ Vaccines) Vol. 7 Issue 1 Pg. 98 (Aug 20 2022) ISSN: 2059-0105 [Electronic] England
• PMID: 35986017 (Publication Type: Journal Article)
• Copyright: © 2022. The Author(s).