title: Intranasal immunisation with recombinant Toxoplasma gondii actin partly protects mice against toxoplasmosis.
abstract: Toxoplasma gondii is a ubiquitous protozoan intracellular parasite, the causative agent of toxoplasmosis, and a worldwide zoonosis for which an effective vaccine is needed. Actin is a highly conserved microfilament protein that plays an important role in the invasion of host cells by T. gondii. This study investigated the immune responses elicited by BALB/c mice after nasal immunisation with a recombinant T. gondii actin (rTgACT) and the subsequent protection against chronic and lethal T. gondii infections. We evaluated the systemic response by proliferation, cytokine and antibody measurements, and we assessed the mucosal response by examining the levels of TgACT-specific secretory IgA (SIgA) in nasal, vaginal and intestinal washes. Parasite load was assessed in the liver and brain, and the survival of mice challenged with a virulent strain was determined. The results showed that the mice immunised with rTgACT developed high levels of specific anti-rTgACT IgG titres and a mixed IgG1/IgG2a response with a predominance of IgG2a. The systemic immune response was associated with increased production of Th1 (IFN-γ and IL-2), Th2 (IL-4) and Treg (IL-10) cytokines, indicating that not only Th1-type response was induced, but also Th2- and Treg-types responses were induced, and the splenocyte stimulation index (SI) was increased in the mice immunised with rTgACT. Nasal immunisation with rTgACT led to strong mucosal immune responses, as seen by the increased secretion of SIgA in nasal, vaginal and intestinal washes. The vaccinated mice displayed significant protection against lethal infection with the virulent RH strain (survival increased by 50%), while the mice chronically infected with RH exhibited lower liver and brain parasite loads (60.05% and 49.75%, respectively) than the controls. Our data demonstrate, for the first time, that actin triggers a strong systemic and mucosal response against T. gondii. Therefore, actin may be a promising vaccine candidate against toxoplasmosis.
authors.affiliation: Department of physiology, Key Laboratory of Cellular Physiology Co-constructed by Province and Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi, PR China.
authors.forename: Li-Tian
authors.initials: LT
authors.lastname: Yin
authors.affiliation: Research Institute of Medical Parasitology, Shanxi Medical University, Taiyuan, Shanxi, PR China ; General Hospital of the Datong Coal Mine Co. Ltd., Datong, Shanxi, PR China.
authors.forename: Hai-Xia
authors.initials: HX
authors.lastname: Hao
authors.affiliation: Research Institute of Medical Parasitology, Shanxi Medical University, Taiyuan, Shanxi, PR China.
authors.forename: Hai-Long
authors.initials: HL
authors.lastname: Wang
authors.affiliation: Research Institute of Medical Parasitology, Shanxi Medical University, Taiyuan, Shanxi, PR China.
authors.forename: Jian-Hong
authors.initials: JH
authors.lastname: Zhang
authors.affiliation: Research Institute of Medical Parasitology, Shanxi Medical University, Taiyuan, Shanxi, PR China.
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Meng
authors.affiliation: Research Institute of Medical Parasitology, Shanxi Medical University, Taiyuan, Shanxi, PR China.
authors.forename: Guo-Rong
authors.initials: GR
authors.lastname: Yin
mesh_terms: D000199:Actins / Q000276:immunology*; D000281:Administration, Intranasal; D000818:Animals; D051379:Mice; D008807:Mice, Inbred BALB C; D015800:Protozoan Proteins / Q000276:immunology*; D016052:Protozoan Vaccines / Q000627:therapeutic use*; D014122:Toxoplasma / Q000276:immunology*; D014124:Toxoplasmosis, Animal / Q000517:prevention & control*; D014611:Vaccination
chemical_list: D000199:Actins; D015800:Protozoan Proteins; D016052:Protozoan Vaccines