title: Induction of protective immune responses by a multiantigenic DNA vaccine encoding GRA7 and ROP1 of Toxoplasma gondii.
abstract: Toxoplasma gondii is distributed worldwide and infects most species of warm-blooded animals, including humans. The heavy incidence and severe or lethal damage caused by T. gondii infection clearly indicates the need for the development of a vaccine. To evaluate the protective efficacy of a multiantigenic DNA vaccine expressing GRA7 and ROP1 of T. gondii with or without a plasmid encoding murine interleukin-12 (pIL12), we constructed DNA vaccines using the eukaryotic plasmids pGRA7, pROP1, and pGRA7-ROP1. Mice immunized with pGRA7, pROP1, or pGRA7-ROP1 showed significantly increased serum IgG2a titers; production of gamma interferon (IFN-γ), IL-10, and tumor necrosis factor alpha (TNF-α); in vitro T cell proliferation; and survival, as well as decreased cyst burdens in the brain, compared to mice immunized with either the empty plasmid, pIL12, or vector with pIL12 (vector+pIL12). Moreover, mice immunized with the multiantigenic DNA vaccine pGRA7-ROP1 had higher IgG2a titers, production of IFN-γ and TNF-α, survival time, and cyst reduction rate compared to those of mice vaccinated with either pGRA7 or pROP1 alone. Furthermore, mice immunized with either a pGRA7-ROP1+pIL12 or a single-gene vaccine combined with pIL12 showed greater Th1 immune response and protective efficacy than the single-gene-vaccinated groups. Our data suggest that the multiantigenic DNA antigen pGRA7-ROP1 was more effective in stimulating host protective immune responses than separately injected single antigens, and that IL-12 serves as a good DNA adjuvant.
authors.affiliation: Department of Infection Biology, Research Institute for Medical Sciences, Chungnam National University School of Medicine, Daejeon, South Korea.
authors.forename: Juan-Hua
authors.initials: JH
authors.lastname: Quan
authors.forename: Jia-Qi
authors.initials: JQ
authors.lastname: Chu
authors.forename: Hassan Ahmed Hassan Ahmed
authors.initials: HA
authors.lastname: Ismail
authors.forename: Wei
authors.initials: W
authors.lastname: Zhou
authors.forename: Eun-Kyeong
authors.initials: EK
authors.lastname: Jo
authors.forename: Guang-Ho
authors.initials: GH
authors.lastname: Cha
authors.forename: Young-Ha
authors.initials: YH
authors.lastname: Lee
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000235:genetics; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology*; D001921:Brain / Q000469:parasitology; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005260:Female; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000008:administration & dosage / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D059208:Parasite Load; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology*; D016052:Protozoan Vaccines / Q000008:administration & dosage / Q000276:immunology*; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology; D014122:Toxoplasma / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D014124:Toxoplasmosis, Animal / Q000276:immunology / Q000517:prevention & control; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; C112573:GRA7 protein, Toxoplasma gondii; D008565:Membrane Proteins; D015800:Protozoan Proteins; D016052:Protozoan Vaccines; C117001:ROP 1 protein, Toxoplasma gondii; D014409:Tumor Necrosis Factor-alpha; D019444:Vaccines, DNA; D018664:Interleukin-12; D007371:Interferon-gamma