title: Prime-boost vaccination with toxoplasma lysate antigen, but not with a mixture of recombinant protein antigens, leads to reduction of brain cyst formation in BALB/c mice.
abstract: BACKGROUND
  Infection with the ubiquitous parasite Toxoplasma gondii is a threat for immunocompromised patients and pregnant women and effective immune-prophylaxis is still lacking.
  
  
  METHODS
  Here we tested a mixture of recombinant T. gondii antigens expressed in different developmental stages, i.e., SAG1, MAG1 and GRA7 (SMG), and a lysate derived from T. gondii tachyzoites (TLA) for prophylactic vaccination against cyst formation. Both vaccine formulations were applied systemically followed by an oral TLA-booster in BALB/c mice.
  
  
  RESULTS
  Systemic priming with SMG and oral TLA-booster did not show significant induction of protective immune responses. In contrast, systemic priming and oral booster with TLA induced higher levels of Toxoplasma-specific IgG, IgG1 and IgG2a in sera as well as high levels of Toxoplasma-specific IgG1 in small intestines. Furthermore, high levels of Toxoplasma-specific Th1-, Th17- and Th2-associated cytokines were only detected in restimulated splenocytes of TLA-vaccinated mice. Importantly, in mice orally infected with T. gondii oocysts, only TLA-vaccination and booster reduced brain cysts. Furthermore, sera from these mice reduced tachyzoites invasion of Vero cells in vitro, indicating that antibodies may play a critical role for protection against Toxoplasma infection. Additionally, supernatants from splenocyte cultures of TLA-vaccinated mice containing high levels of IFN-γ lead to substantial production of nitric oxide (NO) after incubation with macrophages in vitro. Since NO is involved in the control of parasite growth, the high levels of IFN-γ induced by vaccination with TLA may contribute to the protection against T. gondii.
  
  
  CONCLUSIONS
  In conclusion, our data indicate that prime-boost approach with TLA, but not with the mixture of recombinant antigens SMG, induces effective humoral and cellular Toxoplasma-specific responses and leads to significant reduction of cerebral cysts, thereby presenting a viable strategy for further vaccine development against T. gondii infection.
authors.affiliation: Institute of Specific Prophylaxis and Tropical Medicine, Center for Pathophysiology, Infectiology & Immunology, Medical University of Vienna, Vienna, Austria.
authors.forename: Angelika
authors.initials: A
authors.lastname: Wagner
authors.affiliation: Institute of Specific Prophylaxis and Tropical Medicine, Center for Pathophysiology, Infectiology & Immunology, Medical University of Vienna, Vienna, Austria.
authors.forename: Irma
authors.initials: I
authors.lastname: Schabussova
authors.affiliation: Institute of Parasitology, Department of Pathobiology, University of Veterinary Medicine, Vienna, Austria.
authors.forename: Bärbel
authors.initials: B
authors.lastname: Ruttkowski
authors.affiliation: Institute of Parasitology, Department of Pathobiology, University of Veterinary Medicine, Vienna, Austria.
authors.forename: Roman
authors.initials: R
authors.lastname: Peschke
authors.affiliation: Gdansk University of Technology, Faculty of Chemistry, Department of Microbiology, Gdansk, Poland.
authors.forename: Józef
authors.initials: J
authors.lastname: Kur
authors.affiliation: Institute of Environmental Health, Medical University of Vienna, Vienna, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Kundi
authors.affiliation: Institute of Parasitology, Department of Pathobiology, University of Veterinary Medicine, Vienna, Austria.
authors.forename: Anja
authors.initials: A
authors.lastname: Joachim
authors.affiliation: Institute of Specific Prophylaxis and Tropical Medicine, Center for Pathophysiology, Infectiology & Immunology, Medical University of Vienna, Vienna, Austria; Department of Rheumatology & Inflammation Research, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Ursula
authors.initials: U
authors.lastname: Wiedermann
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D000918:Antibody Specificity / Q000276:immunology; D000953:Antigens, Protozoan / Q000276:immunology*; D001921:Brain / Q000469:parasitology* / Q000473:pathology*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D004247:DNA / Q000378:metabolism; D005260:Female; D041981:Gastrointestinal Tract / Q000469:parasitology; D007117:Immunization, Secondary; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000378:metabolism; D015800:Protozoan Proteins / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology*; D013154:Spleen / Q000473:pathology; D014122:Toxoplasma / Q000276:immunology*; D014611:Vaccination
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D016207:Cytokines; D015800:Protozoan Proteins; D011994:Recombinant Proteins; D009569:Nitric Oxide; D004247:DNA