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The influence of adjuvant on UreB protection against Helicobacter pylori through the diversity of CD4+ T-cell epitope repertoire

机译:佐剂通过CD4 + T细胞表位库的多样性对UreB对幽门螺杆菌的保护作用

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摘要

Adjuvants are widely used to enhance the effects of vaccines against pathogen infections. Interestingly, different adjuvants and vaccination routes usually induce dissimilar immune responses, and can even have completely opposite effects. The mechanism remains unclear. In this study, urease B subunit (UreB), an antigen of Helicobacter pylori (H. pylori) that can induce protective immune responses, was used as a model to vaccinate mice. We investigated the effects of different adjuvants and routes on consequent T cell epitope-specific targeting and protection against H. pylori infection. Comparison of the protective effects of UreB, administered either subcutaneously (sc) or intranasally (in), with the adjuvants AddaVax (sc), Complete Freund’s adjuvant (CFA; sc), or CpG oligonucleotide (CpG; sc or in), indicated that only CFA (sc) and CpG (in) were protective. Protective vaccines induced T cells targeting epitopes that differed from that targeted by control vaccination. Subsequent peptide vaccination demonstrated that only two of the identified epitopes were protective: UreB373–385 and UreB317–329. Overall, we found that both adjuvant and vaccination route affected the T cell response repertoire to antigen epitopes. The data obtained in this study contribute to improved characterization of the relationship between adjuvants, routes of vaccination, and epitope-specific T cell response repertoires.
机译:佐剂被广泛用于增强疫苗抵抗病原体感染的作用。有趣的是,不同的佐剂和疫苗接种途径通常会诱导不同的免疫反应,甚至可能产生完全相反的效果。机制尚不清楚。在这项研究中,脲酶B亚基(UreB)是幽门螺杆菌(H. pylori)的一种抗原,可以诱导保护性免疫反应,被用作给小鼠接种的模型。我们调查了不同的佐剂和途径对随后的T细胞表位特异性靶向和针对幽门螺杆菌感染的保护作用。皮下(sc)或鼻内(in)施用UreB与佐剂AddaVax(sc),完全弗氏佐剂(CFA; sc)或CpG寡核苷酸(CpG; sc或in)的保护作用比较表明,只有CFA(sc)和CpG(in)具有保护性。保护性疫苗诱导的T细胞靶向表位不同于对照疫苗靶向。随后的肽疫苗接种表明,只有两个已鉴定的表位具有保护性:UreB373-385和UreB317-329。总体而言,我们发现佐剂和疫苗接种途径均会影响T细胞对抗原表位的反应。这项研究中获得的数据有助于改善佐剂,疫苗接种途径和表位特异性T细胞反应谱之间的关系。

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