Antigenome of Helicobacter pylori: vaccination on the horizon?

Helicobacter pylori is the most prevalent human pathogen with about 50% of the world's population infected. Although, it remains silent in most individuals for lifetime, colonization may develop into severe gastric and duodenal conditions, such as peptic ulcer disease and gastric adenocarcinoma. Rapidly developing resistance to current antibiotic-based treatment regimes urgently calls for the development of effective vaccines. In these studies we determined the comprehensive antigenic profile (so called “ANTIGENome“) of two clinical isolates of H. pylori, KTH-Ca1 and KTH-Du that were derived from patients with gastric cancer and duodenal ulcer, respectively. With the aid of our whole genome-based bacterial surface display technology and disease-relevant human sera from well-characterized donors – including patients with clinically and microbiologically verified Helicobacter diseases and healthy adults – we identified 124 annotated ORFs and 54 non-annotated genomic regions coding for antigens. Through in vitro validation assays we selected the 20 most promising vaccine candidates. Importantly, two of the selected 20 candidates represent proteins that have been previously shown to provide protection in experimental 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.