title: Oral delivery of the Sj23LHD-GST antigen by Salmonella typhimurium type III secretion system protects against Schistosoma japonicum infection in mice.
abstract: BACKGROUND
  Schistosomiasis japonica is a zoonotic parasitic disease and oral vaccine delivery system would be benefit for prevention of this disease. Although attenuated salmonella has been used as an antigen expression vector for oral vaccine development, the membrane-bound vacuoles in which bacteria reside hinders the presentation of expressed heterologous antigens to the major histocompatibility complex (MHC) molecules. The present work used an attenuated Salmonella typhimurium strain VNP20009 to secretory expression of Sj23LHDGST bivalent antigen from Schistosoma japonicum and tested the protective efficacy against S. japonicum infection in orally immunized mice.
  
  
  RESULTS
  Promoters (nirB or pagC) were used to express the antigen (Sj23LHDGST) and the Salmonella type III or α-hemolysin secretion system was employed to secrete it. The immunoblotting analysis and fluorescent microscopy revealed that the antigen was effectively expressed and delivered to the cytosol of macrophages in vitro. Among recombinant vaccine strains, an engineered VNP20009 which expressed the antigen by nirB promoter and secreted it through type III secretion system (nirB-sopE(1-104)-Sj23LHD-GST) efficiently protected against S. japonicum infection in a mouse model. This strain elicited a predominantly IgG(2a) antibody response and a markedly increase in the production of IL-12 and IFN-γ. The flow cytometric analysis demonstrated that this strain caused T cell activation as evidenced by significantly increased expression of CD44 and CD69.
  
  
  CONCLUSIONS
  Oral delivery of antigen by nirB-driven Salmonella typhimurium type III secretion system is a novel, safe, inexpensive, efficient and convenient approach for schistosome vaccine development.
authors: The State Key Laboratory of Pharmaceutical Biotechnology and School of Stomatology, Affiliated Stomatological Hospital, Nanjing University, Nanjing, People's Republic of China.
authors: Guo
authors: G
authors: Chen
authors: Yang
authors: Y
authors: Dai
authors: Jianxiang
authors: J
authors: Chen
authors: Xiaoting
authors: X
authors: Wang
authors: Bo
authors: B
authors: Tang
authors: Yinchang
authors: Y
authors: Zhu
authors: Zichun
authors: Z
authors: Hua
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000909:Antibodies, Helminth / Q000097:blood; D000947:Antigens, Helminth / Q000235:genetics / Q000276:immunology*; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D005243:Feces / Q000469:parasitology; D005260:Female; D005822:Genetic Vectors; D006099:Granuloma / Q000473:pathology / Q000517:prevention & control; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010270:Parasite Egg Count; D012486:Salmonella typhimurium / Q000235:genetics*; D012549:Schistosoma japonicum / Q000235:genetics / Q000276:immunology*; D012554:Schistosomiasis japonica / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D014611:Vaccination / Q000379:methods*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics / Q000276:immunology
chemical_list: D000909:Antibodies, Helminth; D000947:Antigens, Helminth; D001428:Bacterial Vaccines; D007074:Immunoglobulin G; D014614:Vaccines, Synthetic; D018664:Interleukin-12; D007371:Interferon-gamma