title: Therapeutic efficacy of oral immunization with a non-genetically modified Lactococcus lactis-based vaccine CUE-GEM induces local immunity against Helicobacter pylori infection.
abstract: The gastric bacterial pathogen Helicobacter pylori persistently colonizes the gastric mucosa of humans and plays a critical role in the development of gastritis, peptic ulceration and gastric adenocarcinoma. Consequently, the eradication of H. pylori might contribute to the prevention of H. pylori-associated gastric diseases. In this study, a multi-epitope vaccine CTB-UE (CUE) was displayed on the surface of non-genetically modified Lactococcus lactis particles (GEM) to enhance immunogenicity. This particulate vaccine CUE-GEM induced serum and mucosal specific antibody responses against native H. pylori urease and provided potent protection to eliminate H. pylori colonization and relieve gastritis in an H. pylori-infected BALB/c mouse model. The immuno-protective mechanisms are highly associated with CD4(+) Th cell-mediated and humoral immunity, especially local immunity. There might be two main aspects of this association. One aspect is related to the suppression of urease activity by promotion of the production of specific mucosal neutralizing antibody. The other aspect is correlated with alleviating gastritis by regulating the gastric pro-inflammatory cytokine profile, especially IFN-γ and IL-17. These results demonstrated that conjugating antigen vaccines with GEM particles could lead to promising oral therapeutic vaccine formulations against H. pylori infection.
authors: School of Life Science and Technology, China Pharmaceutical University, Nanjing, 210009, People's Republic of China.|Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing, 210009, People's Republic of China.
authors: Wei
authors: W
authors: Liu
authors: School of Life Science and Technology, China Pharmaceutical University, Nanjing, 210009, People's Republic of China.|Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing, 210009, People's Republic of China.
authors: Zhoulin
authors: Z
authors: Tan
authors: School of Life Science and Technology, China Pharmaceutical University, Nanjing, 210009, People's Republic of China.|Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing, 210009, People's Republic of China.
authors: Jinfeng
authors: J
authors: Xue
authors: School of Life Science and Technology, China Pharmaceutical University, Nanjing, 210009, People's Republic of China.|Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing, 210009, People's Republic of China.
authors: Wenjin
authors: W
authors: Luo
authors: School of Life Science and Technology, China Pharmaceutical University, Nanjing, 210009, People's Republic of China.|Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing, 210009, People's Republic of China.
authors: Hui
authors: H
authors: Song
authors: School of Life Science and Technology, China Pharmaceutical University, Nanjing, 210009, People's Republic of China.
authors: Xiaobo
authors: X
authors: Lv
authors: School of Life Science and Technology, China Pharmaceutical University, Nanjing, 210009, People's Republic of China.|Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing, 210009, People's Republic of China.
authors: Tianjing
authors: T
authors: Zheng
authors: School of Life Science and Technology, China Pharmaceutical University, Nanjing, 210009, People's Republic of China. xitao18@hotmail.com.|Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing, 210009, People's Republic of China. xitao18@hotmail.com.
authors: Tao
authors: T
authors: Xi
authors: School of Life Science and Technology, China Pharmaceutical University, Nanjing, 210009, People's Republic of China. xingying1980@126.com.|Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing, 210009, People's Republic of China. xingying1980@126.com.
authors: Yingying
authors: Y
authors: Xing
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000276:immunology; D001428:Bacterial Vaccines / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D005756:Gastritis / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control; D000069196:Gastrointestinal Microbiome; D041981:Gastrointestinal Tract / Q000382:microbiology; D016481:Helicobacter Infections / Q000276:immunology / Q000517:prevention & control*; D016480:Helicobacter pylori / Q000201:enzymology / Q000276:immunology; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007114:Immunization; D007371:Interferon-gamma / Q000097:blood; D020381:Interleukin-17 / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D013294:Lactococcus lactis / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D014510:Urease / Q000276:immunology / Q000378:metabolism
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001428:Bacterial Vaccines; D000939:Epitopes; D020381:Interleukin-17; D015850:Interleukin-6; D015847:Interleukin-4; D007371:Interferon-gamma; D014510:Urease
keywords: Helicobacter pylori; Lactococcus lactis; Mucosal immunity; Therapeutic vaccine