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

Abstract

Toxoplasma gondiihost cellular invasion factors such as the rhoptry proteins, micronemal antigens, or other subcellular compartment proteins have shown limited vaccine efficacies.T.gondiicyst 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 theT.gondiiCST1 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 uponT.gondiiME49 challenge infection compared to unimmunized control. Thus, VLP immunization protected mice from the lethal dose challenge infection withT.gondiiME49 and did not incur bodyweight loss. These results indicated thatT.gondiiCST1 containing VLPs can induce mucosal and systemic immunity and also suggest its developmental potential as an effective vaccine candidate againstT.gondiiinfection.