Meinke Andreas, Storm Martin, Henics Tamás, Gelbmann Dieter, Prustomersky Sonja, Kovács Zoltán, Minh Duc Bui, Noiges Birgit, Stierschneider Ulrike, Berger Manfred, von Gabain Alexander, Engstrand Lars, Nagy Eszter
Intercell AG, Campus Vienna Biocenter 5, A-1030 Vienna, Austria.
Vaccine. 2009 May 26;27(25-26):3251-9. doi: 10.1016/j.vaccine.2009.01.066. Epub 2009 Feb 5.
Helicobacter pylori is the most prevalent human pathogen and although, it remains silent in most individuals for lifetime, colonization may develop into severe gastric and duodenal conditions. Rapidly developing resistance to antibiotic treatment urgently calls for the development of effective vaccines. We determined the ANTIGENome of two clinical isolates of H. pylori, KTH-Ca1 and KTH-Du, derived from patients with gastric cancer and duodenal ulcer, respectively. Using disease-relevant human sera from well-characterized donors we identified 124 annotated ORFs and 54 non-annotated peptides as antigens. Through in vitro validation assays we selected the 20 most promising vaccine candidates. Importantly, two candidates represent proteins that were previously shown to provide protection in models of H. pylori infection. One of the most frequently selected and conserved protein, the siderophore-dependent transporter HP1341, was confirmed to show high reactivity with human serum IgGs. These analyses provide the means to identify novel antigens for the selection of vaccine candidates, as well as disease associated biomarkers.
幽门螺杆菌是最常见的人类病原体，尽管在大多数个体中它会终生保持无症状状态，但定植可能会发展为严重的胃部和十二指肠疾病。抗生素治疗的耐药性迅速发展，迫切需要开发有效的疫苗。我们测定了幽门螺杆菌的两个临床分离株KTH-Ca1和KTH-Du的抗原组，这两个分离株分别来自胃癌和十二指肠溃疡患者。使用来自特征明确的供体的与疾病相关的人类血清，我们鉴定出124个注释的开放阅读框和54个未注释的肽作为抗原。通过体外验证试验，我们选择了20个最有前景的疫苗候选物。重要的是，两个候选物代表的蛋白质先前已证明在幽门螺杆菌感染模型中具有保护作用。最常被选择和保守的蛋白质之一，即铁载体依赖性转运蛋白HP1341，被证实与人血清IgG具有高反应性。这些分析为鉴定用于选择疫苗候选物的新型抗原以及疾病相关生物标志物提供了方法。
