Protective immunity induced by peptides of AMA1, RON2 and RON4 containing T-and B-cell epitopes via an intranasal route against toxoplasmosis in mice

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Abstract

Background: Toxoplasma gondii is a ubiquitous protozoan intracellular parasite, the causative agent of toxoplasmosis, and a worldwide zoonosis. Apical membrane antigen-1 (AMA1) and rhoptry neck protein (RON2, RON4) are involved in the invasion of T. gondii. Methods: This study chemically synthesized peptides of TgAMA1, TgRON2 and TgRON4 that contained the T- and B-cell epitopes predicted by bioinformatics analysis. We evaluated the systemic response by proliferation, cytokine and antibody measurements as well as the mucosal response by examining the levels of antigen-specific secretory IgA (SIgA) in the nasal, vesical and intestinal washes obtained from mice after nasal immunization with single (AMA1, RON2, RON4) or mixtures of peptides (A1∈+∈R2, A1∈+∈R4, R2∈+∈R4, A1∈+∈R2∈+∈R4). We also assessed the parasite burdens in the liver and brain as well as the survival of mice challenged with a virulent strain. Results: The results showed that the mice immunized with single or mixed peptides produced effective mucosal and systemic immune responses with a high level of specific antibody responses, a strong lymphoproliferative response and significant levels of gamma interferon (IFN-γ), interleukin-2 (IL-2) and IL-4 production. These mice also elicited partial protection against acute and chronic T. gondii infection. Moreover, our study indicated that mixtures of peptides, especially the A1∈+∈R2 mixture, were more powerful and efficient than any other single peptides. Conclusions: These results demonstrated that intranasal immunisation with peptides of AMA1, RON2 and RON4 containing T- and B-cell epitopes can partly protect mice against toxoplasmosis, and a combination of peptides as a mucosal vaccine strategy is essential for future Toxoplasma vaccine development.

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Zhang, T. E., Yin, L. T., Li, R. H., Wang, H. L., Meng, X. L., & Yin, G. R. (2015). Protective immunity induced by peptides of AMA1, RON2 and RON4 containing T-and B-cell epitopes via an intranasal route against toxoplasmosis in mice. Parasites and Vectors, 8(1). https://doi.org/10.1186/s13071-015-0636-5

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