title: Protective immunity induced by peptides of AMA1, RON2 and RON4 containing T-and B-cell epitopes via an intranasal route against toxoplasmosis in mice.
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.
authors.affiliation: Research Institute of Medical Parasitology, Shanxi Medical University, Xinjian South Road, Taiyuan, Shanxi Province, 030001, China. zte31@qq.com.|Department of Clinical Laboratory, Central Hospital of the 12th Bureau Group of China Railway, Taiyuan, Shanxi, 030053, China. zte31@qq.com.
authors.forename: Tie-E
authors.initials: TE
authors.lastname: Zhang
authors.affiliation: Department of physiology, Key Laboratory of Cellular Physiology Co-constructed by Province and Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi, 030001, China. yinlitian@126.com.
authors.forename: Li-Tian
authors.initials: LT
authors.lastname: Yin
authors.affiliation: Department of Biology, Taiyuan Normal University, Taiyuan, Shanxi, 030031, China. runhual@163.com.
authors.forename: Run-Hua
authors.initials: RH
authors.lastname: Li
authors.affiliation: Research Institute of Medical Parasitology, Shanxi Medical University, Xinjian South Road, Taiyuan, Shanxi Province, 030001, China. longwty@163.com.
authors.forename: Hai-Long
authors.initials: HL
authors.lastname: Wang
authors.affiliation: Research Institute of Medical Parasitology, Shanxi Medical University, Xinjian South Road, Taiyuan, Shanxi Province, 030001, China. mxltysx@163.com.
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Meng
authors.affiliation: Research Institute of Medical Parasitology, Shanxi Medical University, Xinjian South Road, Taiyuan, Shanxi Province, 030001, China. guorongyin@163.com.
authors.forename: Guo-Rong
authors.initials: GR
authors.lastname: Yin
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D049109:Cell Proliferation; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D018985:Epitopes, B-Lymphocyte / Q000378:metabolism*; D018984:Epitopes, T-Lymphocyte / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D007071:Immunoglobulin A, Secretory; D008214:Lymphocytes / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D010455:Peptides / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology; D016052:Protozoan Vaccines / Q000008:administration & dosage / Q000276:immunology*; D013154:Spleen / Q000166:cytology; D014124:Toxoplasmosis, Animal / Q000517:prevention & control*
chemical_list: D016207:Cytokines; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D007071:Immunoglobulin A, Secretory; D010455:Peptides; D015800:Protozoan Proteins; D016052:Protozoan Vaccines