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Therapeutic efficacy of oral immunization with a non-genetically modified Lactococcus lactis-based vaccine CUE-GEM induces local immunity against Helicobacter pylori infection

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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.

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Acknowledgments

We thank Mr. Zhaohui Wang for his careful revision of this paper.

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Authors and Affiliations

  1. School of Life Science and Technology, China Pharmaceutical University, Nanjing, 210009, People’s Republic of China

    Wei Liu, Zhoulin Tan, Jinfeng Xue, Wenjin Luo, Hui Song, Xiaobo Lv, Tianjing Zheng, Tao Xi & Yingying Xing

  2. Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing, 210009, People’s Republic of China

    Wei Liu, Zhoulin Tan, Jinfeng Xue, Wenjin Luo, Hui Song, Tianjing Zheng, Tao Xi & Yingying Xing

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  1. Wei Liu
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Correspondence to Tao Xi or Yingying Xing.

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Funding

This work was supported by the National Major Special Program of New Drug Research and Development (No. 2012ZX09103301–008), the Natural Science Foundation of Jiangsu Province (No. BK20130647), the Priority Academic Program Development (PAPD) of Jiangsu Higher Education Institutions and Qing Lan Project, the National Natural Science Foundation of China (No. 81502970) and the Fundamental Research Funds for the Central Universities (No. 2015ZD004).

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The authors declare that they have no competing interests.

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All animal experimental procedures were performed in accordance with guidelines of the Animal Ethical and Experimental Committee of China Pharmaceutical University.

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Liu, W., Tan, Z., Xue, J. et al. Therapeutic efficacy of oral immunization with a non-genetically modified Lactococcus lactis-based vaccine CUE-GEM induces local immunity against Helicobacter pylori infection. Appl Microbiol Biotechnol 100, 6219–6229 (2016). https://doi.org/10.1007/s00253-016-7333-y

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