Abstract
The inner membrane complex (IMC) of Toxoplasma gondii as a peripheral membrane system has unique and critical roles in parasite replication, motility and invasion. Disruption of IMC sub-compartment protein produces a severe defect in T. gondii endodyogeny, the form of internal cell budding. In this study, we generated T. gondii virus-like particle particles (VLPs) containing proteins derived from IMC, and investigated their efficacy as a vaccine in mice. VLP vaccination induced Toxoplasma gondii-specific total IgG, IgG1 and IgG2a antibody responses in the sera and IgA antibody responses in the feces. Upon challenge infection with a lethal dose of T. gondii (ME49), all vaccinated mice survived, whereas all naïve control mice died. Vaccinated mice showed significantly reduced cyst load and cyst size in the brain. VLP vaccination also induced IgA and IgG antibody responses in feces and intestines, and antibody-secreting plasma cells, mixed Th1/Th2 cytokines and CD4+/CD8+ T cells from spleen. Taken together, these results indicate that non-replicating VLPs containing inner membrane complex of T. gondii represent a promising strategy for the development of a safe and effective vaccine to control the spread of Toxoplasma gondii infection.
Highlights
Toxoplasma gondii is an obligate intracellular parasite that has adapted to infect many animal species including humans, and is capable of causing a wide spectrum of diseases, permanently infecting nearly 20% of the global population [1]
Sequence analysis indicated that the nucleotide sequences of the T. gondii inner membrane complex (IMC) and influenza matrix protein 1 (M1) genes were identical to previously published sequences
We produced virus-like particle particles (VLPs) in insect cells co-infected with recombinant baculoviruses expressing T. gondii IMC and influenza M1
Summary
Toxoplasma gondii is an obligate intracellular parasite that has adapted to infect many animal species including humans, and is capable of causing a wide spectrum of diseases, permanently infecting nearly 20% of the global population [1]. Human infection occurs through two main routes–ingestion of undercooked meat containing cysts of the parasite and ingestion of oocysts passed into the environment by cats [2]. The symptoms could be asymptomatic, resulting in a latent infection with tissue cysts. The strategy of toxoplasmosis control is chemotherapy targeting the acute phase of the infection. An alternative control strategy for toxoplasmosis is urgently needed. Recent important progress has been made identifying anti-toxoplasma vaccine candidates that can stimulate an immunological response [7].
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