Abstract
Helicobacter pylori has infected more than half of the world's population, causing gastritis, gastric ulcers, gastric mucosa-associated lymphoid tissue lymphoma and gastric cancer. The oral recombinant Helicobacter pylori vaccine currently used has made great progress in addressing this problem, however, its efficacy and longevity still need to be improved. Th1 and Th17 cells play essential roles in local protection against Helicobacter pylori in the stomach mucosa. Additionally, protective immunodominant antigens are the preferred for a vaccine. In this work, Helicobacter pylori whole cell lysate was separated into 30 groups based on molecular weight by molecular sieve chromatography. The group best promoting CD4 T cells proliferation was selected and evaluated by immunization. The detail proteins were then analyzed by LC-MS/MS and expressed in Escherichia coli. Eleven proteins were selected and the dominant ones were demonstrated. As a result, three protective immunodominant antigens, inosine 5'-monophosphate dehydrogenase, type II citrate synthase, and urease subunit beta, were selected from Helicobacter pylori whole cell. Two of them (inosine 5'-monophosphate dehydrogenase and type II citrate synthase) were newly identified, and one (urease subunit beta) was confirmed as previously reported. The mixture of the three antigens showed satisfactory protective efficiency, with significant lower H. pylori colonization level (P < 0.001) and stronger Th1 (P < 0.001) and Th17 (P < 0.001) responses than PBS control group. Thus, inosine 5'-monophosphate dehydrogenase, type II citrate synthase, and urease subunit beta are three protective antigens inducing dominant Th1 and Th17 responses to defend against Helicobacter pylori infection.
Highlights
Helicobacter pylori (H. pylori) is a spiral-shaped, gram-negative bacterium that resides in gastric mucosa
interferon γ (IFN-γ) and interleukin 17A (IL-17A) responses were elicited and mice were protected from H. pylori challenge by H. pylori whole cell immunization
Our data showed that groups with stronger CD4 T cell responses had lower levels of H. pylori colonization in the stomach (Figure 1)
Summary
Helicobacter pylori (H. pylori) is a spiral-shaped, gram-negative bacterium that resides in gastric mucosa. It has infected more than half of the world’s population, causing gastritis, gastric ulcers, gastric mucosa-associated lymphoid tissue lymphoma (MALT) and gastric cancer [1]. Our oral recombinant Helicobacter pylori vaccine has made great progress in addressing this problem [2]. Participants fasted for at least 2 h and were given 80 mL of buffer www.impactjournals.com/oncotarget solution, containing 2.8 g sodium bicarbonate and 1.1 g sodium citrate, 2 min before the oral vaccination. The oral recombinant H. pylori vaccine showed an efficacy of 71.8% (95% CI 48.2–85.6) in the first year, but it decreased sharply to 55.0% (95% CI 0.9–81.0) in the second year.
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