Protective mucosal and systemic immunity induced by virus-like particles expressing Toxoplasma gondii cyst wall
Gi-Deok Eom1, Ki-Back Chu2, Hae-Ji Kang1
1Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul, Korea.
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.
Insights
Influenza virus-like particles (VLPs) expressing Toxoplasma gondii cyst wall protein 1 (CST1) induced robust mucosal and systemic immunity. This novel vaccine candidate significantly reduced parasite load and protected mice against lethal challenge.
Area of Science:
- Parasitology
- Immunology
- Vaccine Development
Background:
- Toxoplasma gondii invasion factors have limited vaccine efficacy.
- T. gondii cyst wall protein (CST1) is crucial for parasite persistence.
Purpose of the Study:
- To evaluate the immunogenicity and efficacy of influenza virus-like particles (VLPs) expressing T. gondii CST1.
- To assess mucosal and systemic immune responses induced by CST1-VLPs.
Main Methods:
- Generation of influenza VLPs displaying T. gondii CST1.
- Intranasal immunization of mice with CST1-VLPs.
- Evaluation of antibody responses, B cell activation, and cytokine production upon T. gondii challenge.
Main Results:
- CST1-VLPs induced parasite-specific IgG and IgA in serum and intestines.
- VLP immunization enhanced germinal center B cell and antibody-secreting cell responses.
- Reduced brain cyst counts and pro-inflammatory cytokines (IFN-γ, IL-6) were observed post-challenge.
- VLP-immunized mice survived lethal T. gondii ME49 challenge without weight loss.
Conclusions:
- T. gondii CST1-containing VLPs effectively induce both mucosal and systemic immunity.
- CST1-VLPs show significant potential as a vaccine candidate against T. gondii infection.
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