title: Protective immune response in mice induced by a suicidal DNA vaccine encoding NTPase-II gene of Toxoplasma gondii.
abstract: DNA-based alphaviral RNA replicon vectors, also called suicidal DNA vectors, have been employed to alleviate biosafety concerns attribution to its ability to induce apoptotic cell death of the transfected cells. Toxoplasma gondii nucleoside triphosphate hydrolase-II (TgNTPase-II), which facilitates the parasite to salvage purines from the host cell for survival and replication, have been demonstrated to be a potential vaccine candidate for toxoplasmosis. Herein, we evaluated the immunogenic potential of a suicidal DNA vaccine encoding TgNTPase-II gene, pDREP-TgNTPase-II, delivered intramuscularly in combination with electroporation. Immunization of mice with pDREP-TgNTPase-II elicited specific humoral responses, with high IgG antibody titers and a mixed IgG1/IgG2a response. The cellular immune response was associated with high level production of IFN-γ, IL-2, IL-10 cytokines and low level IL-4 production as well as the increase of the percentage of CD8+ T cells, indicating that a Th1 predominant response was elicited. Furthermore, mice vaccinated with this suicidal DNA vaccine displayed partial protection against acute infection with the virulent RH strain as well as chronic infection with PRU cyst, which shows 77.7% and 71.4% reduction in brain cyst burden in comparison to PBS and pDREP-eGFP control group, respectively. Based on the cellular and antibody responses, the suicidal DNA vaccine elicited a Th1-predominant immune response against T. gondii challenge.
authors.affiliation: Department of Parasitology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, PR China; School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou 325027, PR China.
authors.forename: Lina
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Department of Parasitology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, PR China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Clinical Laboratory, Dongyang People's Hospital, Jinhua, Zhejiang 322100, PR China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Hua
authors.affiliation: Department of Clinical laboratory, Zhuji People's Hospital, Zhuji, Zhejiang 311800, PR China.
authors.forename: Fangjun
authors.initials: F
authors.lastname: Luo
authors.affiliation: Department of Parasitology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, PR China.
authors.forename: Guizhen
authors.initials: G
authors.lastname: Xie
authors.affiliation: Department of Parasitology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, PR China.
authors.forename: Xiangzhi
authors.initials: X
authors.lastname: Li
authors.affiliation: School of Medical Laboratory Science and School of Life Science, Wenzhou Medical University, Wenzhou, Zhejiang 325035, PR China.
authors.forename: Jiaxin
authors.initials: J
authors.lastname: Lin
authors.affiliation: Department of Parasitology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, PR China.
authors.forename: Yujing
authors.initials: Y
authors.lastname: Wan
authors.affiliation: Department of Parasitology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, PR China.
authors.forename: Shoufeng
authors.initials: S
authors.lastname: Ren
authors.affiliation: Department of Parasitology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, PR China. Electronic address: wzpcw@sohu.com.
authors.forename: Changwang
authors.initials: C
authors.lastname: Pan
authors.affiliation: Department of Parasitology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, PR China. Electronic address: tanfengsong@163.com.
authors.forename: Feng
authors.initials: F
authors.lastname: Tan
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D007111:Immunity, Cellular; D007074:Immunoglobulin G / Q000378:metabolism; D007273:Injections, Intramuscular; D051379:Mice; D008807:Mice, Inbred BALB C; D043583:Nucleoside-Triphosphatase / Q000235:genetics*; D015800:Protozoan Proteins / Q000235:genetics*; D016052:Protozoan Vaccines / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology; D014122:Toxoplasma / Q000235:genetics / Q000276:immunology*; D014124:Toxoplasmosis, Animal / Q000276:immunology / Q000517:prevention & control*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D016207:Cytokines; D007074:Immunoglobulin G; D015800:Protozoan Proteins; D016052:Protozoan Vaccines; D019444:Vaccines, DNA; D043583:Nucleoside-Triphosphatase
keywords: Alphavirus Semliki Forest virus (SFV); Nucleoside triphosphate hydrolase; Suicidal DNA vaccine; Toxoplasma gondii