Immunodominant epitope-specific Th1 but not Th17 responses mediate protection against Helicobacter pylori infection following UreB vaccination of BALB/c mice

BALB/c 小鼠接种 UreB 疫苗后,免疫优势表位特异性 Th1 而非 Th17 反应可介导对幽门螺杆菌感染的保护

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作者:Bin Li, Li Chen, Heqiang Sun, Wuchen Yang, Jian Hu, Yafei He, Shanshan Wei, Zhuo Zhao, Jinyong Zhang, Haibo Li, Quanming Zou, Chao Wu

Abstract

Helicobacter pylori (H. pylori) infects more than half of the world's population, causing chronic gastritis, peptic ulcers and gastric cancer. Urease B subunit (UreB), a conserved protein of H. pylori, is capable of inducing specific CD4(+) T-cell responses and provides protection against this infection. Previous studies have confirmed the effectiveness of rUreB subunit vaccines in generating CD4(+) T-cell-mediated protection, but less is known regarding the roles of different subtypes of T-cell immunity, such as Th1, Th2 and Th17, particularly the immunodominant epitopes inducing specific CD4(+) T-cell responses, in vaccine-mediated protection. In this study, we demonstrated that the vaccination of BALB/c mice with rUreB resulted in significant antigen-specific Th1 and Th17 immune responses. Importantly, two novel Th epitopes, UreB317-329 and UreB409-421, which are recognized by a major population of CD4(+) T cells, were identified in immunized mice. Our results demonstrated that two novel epitopes can simultaneously induce Th1 and Th17 immune responses; however, only the epitope vaccine-induced CD4(+) T-cells secreting IFN-γ mediated the protection against H. pylori; cells secreting IL-17A did not. Taken together, our results suggest that two novel immunodominant epitopes can induce Th1 and Th17 immune responses, but only the induced Th1 lymphocytes mediate protection against H. pylori.

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