Live-attenuated ME49Δcdpk3 strain of Toxoplasma gondii protects against acute and chronic toxoplasmosis.
Minmin WuShutong LiuYing ChenDeng LiuRan AnHaijian CaiJie WangNan ZhouCudjoe ObedMeng HanJi-Long ShenLijian ChenJian DuPublished in: NPJ vaccines (2022)
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.
Keyphrases
- toxoplasma gondii
- wild type
- immune response
- escherichia coli
- drug induced
- public health
- liver failure
- dendritic cells
- respiratory failure
- protein kinase
- pseudomonas aeruginosa
- aortic dissection
- rheumatoid arthritis
- high glucose
- type diabetes
- adipose tissue
- metabolic syndrome
- artificial intelligence
- big data
- hepatitis b virus
- biofilm formation
- human health
- machine learning
- reactive oxygen species