title: DNA immunization with eukaryotic initiation factor-2α of Toxoplasma gondii induces protective immunity against acute and chronic toxoplasmosis in mice.
abstract: Toxoplasma gondii infection is a serious health problem of humans and animals worldwide. T. gondii eukaryotic initiation factor-2α (TgIF2α) plays a crucial role in parasite viability and is an important virulence factor of T. gondii. To evaluate the vaccine potential of TgIF2α, we constructed a novel eukaryotic plasmid pVAX-IF2α expressing TgIF2α from the RH strain and validated expression and immunogenicity in vitro in the Marc145 cell expression system by indirect immunofluorescence (IFA). Administration of pVAX-IF2α intramuscularly induced specific humoral immune responses including high levels of specific TgIF2α IgG antibody and a mixed IgG1/IgG2a response with a predominance of IgG2a production. The cellular immune response was elicited, showing significant production of IFN-γ and IL-2 associated with Th1 type response, and thus strong cell-mediated cytotoxic activity with increased frequencies of IFN-γ parameters analyzed in both CD4(+) and CD8(+) T cell compartments (CD4(+) IFN-γ(+) T cells and CD8(+) IFN-γ(+) T cells). Immunization resulted in partial protection against acute and chronic toxoplamosis in outbred Kunming mice, demonstrated by a significantly prolonged survival time (15.9±4.6 days) after challenge with the virulent RH strain and significant reduction in brain cysts (44.1%) against chronic infection with PRU cyst in contrast to control mice. Our data suggested that pVAX-IF2α could be used as a DNA vaccine candidate against both acute and chronic T. gondii infection by the activation of effective humoral and cellular immune responses.
authors.affiliation: State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu Province 730046, PR China.
authors.forename: Jia
authors.initials: J
authors.lastname: Chen
authors.forename: Si-Yang
authors.initials: SY
authors.lastname: Huang
authors.forename: Dong-Hui
authors.initials: DH
authors.lastname: Zhou
authors.forename: Zhong-Yuan
authors.initials: ZY
authors.lastname: Li
authors.forename: Eskild
authors.initials: E
authors.lastname: Petersen
authors.forename: Hui-Qun
authors.initials: HQ
authors.lastname: Song
authors.forename: Xing-Quan
authors.initials: XQ
authors.lastname: Zhu
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D001921:Brain / Q000469:parasitology / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D015852:Eukaryotic Initiation Factor-2 / Q000235:genetics / Q000276:immunology*; D005260:Female; D007074:Immunoglobulin G / Q000097:blood; D007273:Injections, Intramuscular; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D051379:Mice; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology; D016052:Protozoan Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology*; D016019:Survival Analysis; D018417:Th1 Cells / Q000276:immunology; D014122:Toxoplasma / Q000235:genetics / Q000276:immunology*; D014124:Toxoplasmosis, Animal / Q000276:immunology / Q000469:parasitology / Q000473:pathology / Q000517:prevention & control*; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology*; D037521:Virulence Factors / Q000235:genetics / Q000276:immunology
chemical_list: D000913:Antibodies, Protozoan; D015852:Eukaryotic Initiation Factor-2; D007074:Immunoglobulin G; D007376:Interleukin-2; D015800:Protozoan Proteins; D016052:Protozoan Vaccines; D019444:Vaccines, DNA; D037521:Virulence Factors; D007371:Interferon-gamma
keywords: DNA vaccine; Eukaryotic initiation factor-2α (TgIF2α); Mice; Protective immunity; Toxoplasma gondii; Toxoplasmosis