Immunodominant antigens that induce Th1 and Th17 responses protect mice against Helicobacter pylori infection

// Heqiang Sun 1 , Hanmei Yuan 1 , Ranjing Tan 2 , Bin Li 1 , Gang Guo 1 , Jinyong Zhang 1 , Haiming Jing 1 , Yi Qin 1 , Zhuo Zhao 1 , Quanming Zou 1 and Chao Wu 1 1 National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing, PR China 2 Department of Dermatology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, PR China Correspondence to: Chao Wu, email: wuchao99261@163.com Quanming Zou, email: qmzou2007@163.com Zhuo Zhao, email: zhaozhuo198309@163.com Keywords: Helicobacter pylori; vaccine; th1 cell; th17 cell; immunodominant response Received: August 08, 2017      Accepted: October 30, 2017      Published: January 03, 2018 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.