4.7 Article

Synthetic Self-Adjuvanted Lipopeptide Vaccines Conferred Protection against Helicobacter pylori Infection

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ADVANCED HEALTHCARE MATERIALS
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WILEY
DOI: 10.1002/adhm.202300085

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Helicobacter pylori; lipopeptide vaccines; mucosal response; self-adjuvant

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Helicobacter pylori (H. pylori) colonizes the stomach epithelium of half the world's population, causing various digestive diseases and stomach cancer. Synthetic lipopeptide vaccines Hp4 and Hp10 can activate bone marrow derived dendritic cells (BMDCs), inducing secretion of cytokines and improving T-cell activation and differentiation. Hp10 provides protection against H. pylori infection by inducing specific sIgA response at mucosal sites. Interestingly, combination of Hp4 and Hp10 enhances protective response against H. pylori infection, with improved T-cell and mucosal antibody responses.
Helicobacter pylori (H. pylori) colonizes the stomach epithelium of half the world's population and is responsible for various digestive diseases and even stomach cancer. Vaccine-mediated protection against H. pylori infection depends primarily on the specific mucosal and T-cell responses. In this study, the synthetic lipopeptide vaccines, Hp4 (Pam(2)Cys modified UreB T-cell epitope) and Hp10 (Pam(2)Cys modified CagA T/B cell combined epitope), not only induce the bone marrow derived dendritic cells (BMDCs) maturation by activating a variety of pattern-recognition receptors (PRRs) such as Toll-like receptor (TLR), Nod-like receptor (NLR), and retinoic acid-inducing gene (RIG) I-like receptor (RLR), and but also stimulate BMDCs to secret cytokines that have the potential to modulate T-cell activation and differentiation. Although intranasal immunization with Hp4 or Hp10 elicits robust epitope-specific T-cell responses in mice, only Hp10 confers protection against H. pylori infection, possibly due to the fact that Hp10 also induces substantial specific sIgA response at mucosal sites. Interestingly, Hp4 elevates the protective response against H. pylori infection of Hp10 when administrated in combination, characterized by better protective effect and enhanced specific T-cell and mucosal antibody responses. The results suggest that synthetic lipopeptide vaccines based on the epitopes derived from the protective antigens are promising candidates for protection against H. pylori infection.

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