Protective mucosal and systemic immunity induced by virus-like particles expressing Toxoplasma gondii cyst wall protein

Abstract

Toxoplasma gondii host cellular invasion factors such as the rhoptry proteins, micronemal antigens, or other subcellular compartment proteins have shown limited vaccine efficacies. T. gondii cyst wall protein (CST1) as a cyst persistence factor is critical for cyst wall integrity and bradyzoite persistence. Here, we generated influenza virus-like particles (VLPs) expressing the T. gondii CST1 and evaluated the mucosal as well as systemic immunities induced by VLPs. Intranasal immunization with the VLPs induced parasite-specific IgG and IgA antibody responses in sera and intestines. VLP immunization showed higher levels of germinal center B cell response and antibody-secreting cell (ASC) response upon challenge infection, indicating memory B cell response was induced. VLP-immunized mice showed a significant reduction of cyst counts and lower levels of pro-inflammatory cytokines (IFN-γ, IL-6) production in the brain upon T. gondii ME49 challenge infection compared to unimmunized control. Thus, VLP immunization protected mice from the lethal dose challenge infection with T. gondii ME49 and did not incur bodyweight loss. These results indicated that T. gondii CST1 containing VLPs can induce mucosal and systemic immunity and also suggest its developmental potential as an effective vaccine candidate against T. gondii infection.

Mucosal adjuvanticity and mucosal booster effect of colibactin-depleted probiotic Escherichia coli membrane vesicles

“…It has been reported that the nasal virus-like particle (VLP) vaccine, an alternative nanoparticle-based vaccine modality, triggered effective CSR to IgG/A to not only virus, 40 , 41 but also bacteria 42 or protozoa. 43 Given that the morphology of CPS14 + MVs resembles that of native viral virion (approximately 100 nm in diameter), the MV-based vaccine might induce potent immune responses through a nanopaticle-dependent manner similar to that of the VLP vaccine displaying antigens. 40 …”