Abstract
The human gastric pathogen Helicobacter pylori (H. pylori) is a successful colonizer of the stomach. H. pylori infection strongly correlates with the development and progression of chronic gastritis, peptic ulcer disease, and gastric malignances. Vaccination is a promising strategy for preventing H. pylori infection. In this study, we evaluated the candidate antigens heat shock protein A (HspA) and H. pylori γ-glutamyl transpeptidase (GGT) for their effectiveness in development of subunit vaccines against H. pylori infection. rHspA, rGGT, and rHspA-GGT, a fusion protein based on HspA and GGT, were constructed and separately expressed in Escherichia coli and purified. Mice were then immunized intranasally with these proteins, with or without adjuvant. Immunized mice exhibited reduced bacterial colonization in stomach. The highest reduction in bacterial colonization was seen in mice immunized with the fusion protein rHspA-GGT when paired with the mucosal adjuvant LTB. Protection against H. pylori colonization was mediated by a strong systemic and localized humoral immune response, as well as a balanced Th1/Th2 cytokine response. In addition, immunofluorescence microscopy confirmed that rHspA-GGT specific rabbit antibodies were able to directly bind H. pylori in vitro. These results suggest antibodies are essential to the protective immunity associated with rHspA-GGT immunization. In summary, our results suggest HspA and GGT are promising vaccine candidates for protection against H. pylori infection.
Highlights
Helicobacter pylori (H. pylori), a spiral-shaped gram negative bacterium that colonizes the stomach of more than 50% of the world’s population, is the cause of chronic gastritis and pepticPLOS ONE | DOI:10.1371/journal.pone.0130391 June 23, 2015Active Immunization against Helicobacter pylori ulcers and is a risk factor for gastric cancer [1]
heat shock protein A (HspA), a member of the GroES chaperone family, is a 13 kDa cytoplasmic protein that located on the bacterial cell surface [20]
HspA harbors a unique C-terminal domain consisting of 28 residues, which is thought to be crucial for binding metal ions [20]
Summary
Active Immunization against Helicobacter pylori ulcers and is a risk factor for gastric cancer [1] This pathogen could not be effectively cleared or prevented from re-infection by host immune system after successful antimicrobial treatment, it usually causes chronic infection, with colonization persisting for the lifetime of the host [2]. Due to drawbacks like antibiotic resistance, adverse reactions to treatment, re-infection and poor patient compliance, antibiotic therapy does not always work well [4]. For these reasons, in order to prevent infection or treat and already established infection, vaccination is considered a promising and reliable alternative approach for the clinical management of H. pylori infections
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