title: Partial protective immunity against toxoplasmosis in mice elicited by recombinant Toxoplasma gondii malate dehydrogenase.
abstract: Toxoplasma gondii can infect humans and wildlife, sometimes causing serious clinical presentations. Currently, no viable vaccine or effective drug strategies exist to prevent and control toxoplasmosis. T. gondii malate dehydrogenase (TgMDH) is a crucial enzyme in cellular redox reactions and has been shown to be an immunogenic compound that could be a potential vaccine candidate. Here, we investigate the protective efficacy of recombinant TgMDH (rTgMDH) against T. gondii infection in BALB/c mice. All mice were vaccinated via the nasal route. We determined the optimal vaccination dose by monitoring systemic and mucosal immune responses. The results showed that mice vaccinated with 30 μg of rTgMDH produced the highest antibody titers in serum, a strong lymphoproliferative response, marked increases in their levels of IL-2 and IFN-γ, and significantly greater levels of specific secretory IgA (sIgA) in mucosal washes. In addition, the vaccinated mice were orally challenged with tachyzoites of the virulent T. gondii RH strain 2 weeks after the final vaccination. Compared to the control group, we found that vaccination with rTgMDH increased the survival rate of infected mice by 47% and also significantly reduced the tachyzoite loads in their liver (by 58%) and brain (by 41%). Therefore, the rTgMDH protein triggers a strong systemic and mucosal immune response and provides partial protection against T. gondii infection.
authors.affiliation: National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, Key Laboratory of Parasite and Vector Biology, MOH, China; National Center for International Research on Tropical Diseases, China; WHO Collaborating Center for Tropical Diseases, Shanghai 200025, China; Department of Pathogenic Biology and Immunology, Laboratory of Infection and Immunity, Xuzhou Medical College, Xuzhou, Jiangsu 221004, China. Electronic address: liouzhuanzhuan12@163.com.
authors.forename: Zhuanzhuan
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Pathogenic Biology and Immunology, Laboratory of Infection and Immunity, Xuzhou Medical College, Xuzhou, Jiangsu 221004, China. Electronic address: yuanfei0910@163.com.
authors.forename: Fei
authors.initials: F
authors.lastname: Yuan
authors.affiliation: Department of Pathogenic Biology and Immunology, Laboratory of Infection and Immunity, Xuzhou Medical College, Xuzhou, Jiangsu 221004, China. Electronic address: yanpingyang83@163.com.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Physiology, Shanxi Medical University, Taiyuan, Shanxi 030001, China. Electronic address: liuyisheng52@163.com.
authors.forename: Litian
authors.initials: L
authors.lastname: Yin
authors.affiliation: Department of Pathogenic Biology and Immunology, Laboratory of Infection and Immunity, Xuzhou Medical College, Xuzhou, Jiangsu 221004, China. Electronic address: yinlitian@gmail.com.
authors.forename: Yisheng
authors.initials: Y
authors.lastname: Liu
authors.affiliation: National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, Key Laboratory of Parasite and Vector Biology, MOH, China; National Center for International Research on Tropical Diseases, China; WHO Collaborating Center for Tropical Diseases, Shanghai 200025, China. Electronic address: wangyanjuan1036@126.com.
authors.forename: Yanjuan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pathogenic Biology and Immunology, Laboratory of Infection and Immunity, Xuzhou Medical College, Xuzhou, Jiangsu 221004, China. Electronic address: ZKY02@163.com.
authors.forename: Kuiyang
authors.initials: K
authors.lastname: Zheng
authors.affiliation: National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, Key Laboratory of Parasite and Vector Biology, MOH, China; National Center for International Research on Tropical Diseases, China; WHO Collaborating Center for Tropical Diseases, Shanghai 200025, China. Electronic address: caojp@yahoo.com.
authors.forename: Jianping
authors.initials: J
authors.lastname: Cao
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D001921:Brain / Q000469:parasitology; D016207:Cytokines / Q000276:immunology; D005260:Female; D018928:Immunity, Mucosal; D007071:Immunoglobulin A, Secretory / Q000276:immunology; D008099:Liver / Q000469:parasitology; D008291:Malate Dehydrogenase / Q000008:administration & dosage / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D015800:Protozoan Proteins / Q000008:administration & dosage / Q000276:immunology*; D016052:Protozoan Vaccines / Q000276:immunology*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology; D014122:Toxoplasma / Q000201:enzymology*; D014124:Toxoplasmosis, Animal / Q000517:prevention & control*
chemical_list: D000913:Antibodies, Protozoan; D016207:Cytokines; D007071:Immunoglobulin A, Secretory; D015800:Protozoan Proteins; D016052:Protozoan Vaccines; D011994:Recombinant Proteins; D008291:Malate Dehydrogenase
keywords: Malate dehydrogenase; Mice; Mucosal immunity; Nasal vaccine; Toxoplasma gondii