Immunization with Heat Shock Protein A and γ-Glutamyl Transpeptidase Induces Reduction on the <i>Helicobacter pylori</i> Colonization in Mice

<div><p>The human gastric pathogen <i>Helicobacter pylori</i> (<i>H</i>. <i>pylori</i>) is a successful colonizer of the stomach. <i>H</i>. <i>pylori</i> infection strongly correlates with the development and progression of chronic gastritis, peptic ulcer disease, and gastric malignances. Vaccination is a promising strategy for preventing <i>H</i>. <i>pylori</i> infection. In this study, we evaluated the candidate antigens heat shock protein A (HspA) and <i>H</i>. <i>pylori</i> γ-glutamyl transpeptidase (GGT) for their effectiveness in development of subunit vaccines against <i>H</i>. <i>pylori</i> infection. rHspA, rGGT, and rHspA-GGT, a fusion protein based on HspA and GGT, were constructed and separately expressed in <i>Escherichia coli</i> 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 <i>H</i>. <i>pylori</i> 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 <i>H</i>. <i>pylori in vitro</i>. 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 <i>H</i>. <i>pylori</i> infection.</p>