Abstract
Toxoplasma gondii (T. gondii) microneme protein 8 (MIC8) represents a novel, functional distinct invasion factor. In this study, we generated virus-like particles (VLPs) targeting Toxoplasma gondii MIC8 for the first time, and investigated the protection against highly virulent RH strain of T. gondii in a mouse model. We found that VLP vaccination induced Toxoplasma gondii-specific IgG and IgG1 antibody responses in the sera. Upon challenge infection with RH strain of T. gondii tachyzoites, vaccinated mice showed a significant increase of both IgG antibodies in sera and IgA antibodies in feces compared to those before challenge, and a rapid expansion of both germinal center B cell (B220+, GL7+) and T cell (CD4+, CD8+) populations. Importantly, intranasally immunized mice showed higher neutralizing antibodies and displayed no proinflammatory cytokine IFN-γ in the spleen. Mice were completely protected from a lethal challenge infection with the highly virulent T. gondii (RH) showing no body weight loss (100% survival). Our study shows the effective protection against T. gondii infection provided by VLPs containing microneme protein 8 of T. gondii, thus indicating a potential T. gondii vaccine candidate.
Highlights
Toxoplasmosis represents a parasite disease caused by T. gondii, which is estimated to infect half of the world’s population [1]
We have previously demonstrated the protective efficacy of virus-like particles (VLPs) containing inner membrane complex (IMC) by measuring 100% survival rate of vaccinated mice upon challenge infection [5]
Higher levels of T. gondii-specific IgG or immunoglobulin A (IgA) antibodies were detected in serum at day 5 upon challenge or feces during days 1 to 7 upon challenge (Fig 4A and 4B; ÃÃP < 0.01) in IN mice groups. These results indicate that IgG and IgA antibodies were rapidly boosted by challenge infection with T. gondii, indicating IN administration induced higher levels of systemic and mucosal antibody responses upon challenge infections
Summary
Toxoplasmosis represents a parasite disease caused by T. gondii, which is estimated to infect half of the world’s population [1]. No human or veterinary vaccine against T. gondii has been licensed to date For this purpose, recombinant protein vaccines have been extensively investigated as a potential vaccine candidate using surface antigens [6,7], rhoptry antigens [8,9], dense granule proteins [7,10] and microneme proteins [11,12,13]. Recombinant protein vaccines have been extensively investigated as a potential vaccine candidate using surface antigens [6,7], rhoptry antigens [8,9], dense granule proteins [7,10] and microneme proteins [11,12,13]
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