Virus-Like Nanoparticle Vaccine Confers Protection against Toxoplasma gondii

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.

Evaluation of CpG-ODN-Adjuvanted Toxoplasma gondii Virus-Like Particle Vaccine upon One, Two, and Three Immunizations

“…All animal experiments were performed following the institutional animal care and use institutional animal care and use committee (IACUC) guidelines (permit number: KHUASP (SE)-18-050). T. gondii ME49 and RH strains were maintained and used for experimental infections as previously described [ 23 , 24 ].…”

Toxoplasma gondii virus‐like particle vaccination alleviates inflammatory response in the brain upon T gondii infection

“…In spite of these efforts, vaccine incorporating the aforementioned strategies failed to provide sufficient protection in mice. Contrastingly, our previous works have demonstrated that virus‐like particles (VLPs) vaccines expressing various T gondii proteins could provide adequate protection against T gondii ME49 in murine models 9‐11 . However, reduced inflammatory responses in the brain induced by VLPs immunization upon T gondii ME49 infection has not been investigated in any of the previous works.…”

Recent progress in microneme-based vaccines development againstToxoplasma gondii

“…VLP vaccines can stimulate powerful humoral and cellular immune responses, representing one of the most appealing approaches for a vaccine platform by mimicking the main structural and functional characteristics of viruses [ 101 102 ]. Moreover, they can be produced in insect cell expression systems, where foreign antigens can be displayed [ 102 ]. It has been reported that VLPs are being useful and safe as vaccine candidates that could provide stronger and longer-lasting protection against toxoplasmosis [ 98 ].…”