Immunodominant antigens that induce Th1 and Th17 responses protect mice againstHelicobacter pyloriinfection

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.

Perivascular Lymphocyte Clusters Induced by Gastric Subserous Layer Vaccination Mediate Optimal Immunity against Helicobacter through Facilitating Immune Cell Infiltration and Local Antibody Response

“…pylori response [22,25,26]. We found here that the perivascular lymphocyte clusters were "expressways" that allowed immune cell emigration into infected gastric mucosa.…”

“…Circulating immune cells (such as Th1/Th17 cells) permeate across postcapillary venules and infiltrate into the mucosa to induce protection against mucosal pathogens [4]. The role of Th1/Th17 cell-mediated post immunization gastritis is highlighted in the anti-Helicobacter pylori response [21,22]. Our primary experiment found that new vessels with perivascular lymphocyte clusters emerged in the vaccination region after resolution of GSL vaccination-induced inflammation.…”

Selected commensal bacteria change profiles of Helicobacter pylori‐induced T cells via dendritic cell modulation

“…These data indicate that the decline in Treg population may be beneficial, as it may enhance protective immunity against Hp. This hypothesis was supported by the results of research on anti-Hp vaccines, which demonstrated a protective role of Th1/Th17 response 55,61,62. Therefore, it appears that both the Th1 and Th17 responses can be effective in Hp erad-…”

Silk fibroin hydrogel as mucosal vaccine carrier: induction of gastric CD4+TRM cells mediated by inflammatory response induces optimal immune protection against Helicobacter felis

“…In our previous study, an alum-based vaccine caused granulation formation in the stomach [ 8 ], and we could not ignore the chronic cognitive dysfunction, toxicity and autoimmunity induced by alum adjuvant [ 36 – 38 ]. In contrast, SF has the advantages of slow release, absorption, and in situ gelatinization in various tissues [ 40 , 41 ], SF has been used as a medicinal transmission system [ 42–44 ] and as a fixed culture of mesenchymal cells in vivo [ 45 ]. In this study, SF, as a vaccine carrier, not only reduced stomach damage but also resulted in pronounced infiltration and generation of gastric intraepithelial CD4+T RM cells.…”