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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• 作者：Tie-E Zhang ; Li-Tian Yin ; Run-Hua Li ; Hai-Long Wang ; Xiao-Li Meng…
• 关键词：Toxoplasma gondii ; AMA1 ; RON2 ; RON4 ; Peptide epitope ; Mucosal vaccine
• 刊名：Parasites & Vectors
• 出版年：2015
• 出版时间：December 2015
• 年：2015
• 卷：8
• 期：1
• 全文大小：1,382 KB
• 参考文献：1. Dubey JP, Lindsay DS, Speer CA. Structures of / Toxoplasma gondii tachyzoites, bradyzoites, and sporozoites and biology and development of tissue cysts. Clin Microbiol Rev. 1998;11:267-9.
  2. Derouin F, Pelloux H. Prevention of toxoplasmosis in transplant patients. Clin Microbiol Infect. 2008;14:1089-01. CrossRef
  3. Innes EA. A brief history and overview of / Toxoplasma gondii. Zoonoses Public Health. 2010;57:1-. CrossRef
  4. Tenter AM, Heckeroth AR, Weiss LM. / Toxoplasma gondii: from animals to humans. Int J Parasitol. 2000;30:1217-8. CrossRef
  5. Andiappan H, Nissapatorn V, Sawangjaroen N, Nyunt M, Lau Y, Khaing S, et al. Comparative study on / Toxoplasma infection between Malaysian and Myanmar pregnant women. Parasites Vectors. 2014;7:564-7. CrossRef
  6. Iijima H, Takahashi I, Kiyono H. Mucosal immune network in the gut for the control of infectious diseases. Rev Med Virol. 2001;11:117-3. CrossRef
  7. Jongert E, Roberts CW, Gargano N, F?rster-Waldl E, Petersen E. Vaccines against / Toxoplasma gondii: challenges and opportunities. Mem Inst Oswaldo Cruz. 2009;104:252-6. CrossRef
  8. Mital J, Meissner M, Soldati D, Ward GE. Conditional expression of / Toxoplasma gondii apical membrane antigen-1 (TgAMA1) demonstrates that TgAMA1 plays a critical role in host cell invasion. Mol Biol Cell. 2005;16:4341-. CrossRef
  9. Crawford J, Tonkin ML, Grujic O, Boulanger MJ. Structural characterization of apical membrane antigen 1 (AMA1) from / Toxoplasma gondii. J Biol Chem. 2010;285:15644-2. CrossRef
  10. Santos JM, Ferguson DJ, Blackman MJ, Soldati-Favre D. Intramembrane cleavage of AMA1 triggers / Toxoplasma to switch from an invasive to a replicative mode. Science. 2010;331:473-. CrossRef
  11. Tyler JS, Treeck M, Boothroyd JC. Focus on the ringleader: the role of AMA1 in apicomplexan invasion and replication. Trends Parasitol. 2011;27:410-0. CrossRef
  12. Alexander DL, Mital J, Ward GE, Bradley P, Boothroyd JC. Identification of the moving junction complex of / Toxoplasma gondii: a collaboration between distinct secretory organelles. PLoS Pathog. 2005;1:e17. CrossRef
  13. Besteiro S, Michelin A, Poncet J, Dubremetz J-F, Lebrun M. Export of a / Toxoplasma gondii rhoptry neck protein complex at the host cell membrane to form the moving junction during invasion. PLoS Pathog. 2009;5:e1000309. CrossRef
  14. Lamarque M, Besteiro S, Papoin J, Roques M, Vulliez-Le Normand B, Morlon-Guyot J, et al. The RON2-AMA1 interaction is a critical step in moving junction dependent invasion by apicomplexan parasites. PLoS Pathog. 2011;7:e1001276. CrossRef
  15. Tyler JS, Boothroyd JC. The C-terminus of / Toxoplasma RON2 provides the crucial link between AMA1 and the host-associated invasion complex. PLoS Pathog. 2011;7:e1001282. CrossRef
  16. Lebrun M, Michelin A, El Hajj H, Poncet J, Bradley PJ, Vial H, et al. The rhoptry neck protein RON4 relocalizes at the moving junction during / Toxoplasma gondii invasion. Cell Microbiol. 2005;7:1823-3. CrossRef
  17. Dautu G, Munyaka B, Carmen G, Zhang G, Omata Y, Xuenan X, et al. / Toxoplasma gondii
• 刊物主题：Parasitology; Infectious Diseases; Tropical Medicine; Entomology;
• 出版者：BioMed Central
• ISSN：1756-3305

文摘

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.