PMID- 31629103 OWN - NLM STAT- MEDLINE DCOM- 20210726 LR - 20231213 IS - 1096-0023 (Electronic) IS - 1043-4666 (Linking) VI - 126 DP - 2020 Feb TI - Co-expression of Interleukin-17A molecular adjuvant and prophylactic Helicobacter pylori genetic vaccine could cause sterile immunity in Treg suppressed mice. PG - 154866 LID - S1043-4666(19)30295-9 [pii] LID - 10.1016/j.cyto.2019.154866 [doi] AB - The increasing clinical significance of Helicobacter pylori (H. pylori) in human stomach cancer has led to global efforts to eradicate this pathogen. Recent studies have confirmed the importance of some cytokines such as Interleukin-18 (IL-18), Interleukin-8 (IL-8), Interleukin-17A (IL-17A) and Interleukin-22 (IL-22) in the pathogenesis of the so-called bacterium. This study was designed to compare the effects of Type 1T helper (Th1), Type 2T helper (Th2) cells, Regulatory T cells (Treg) and T helper 17 (Th17) modulatory effects on the efficacy of designed H. pylori vaccine by incorporating some molecular adjuvants in Treg competent and Treg suppressed groups. A bicistronic vector was used for simultaneous expression of codon-optimized Outer inflammatory protein a (OipA) gene and modified mice IL-18, IL-17A, IL-22 and Foxp3 (forkhead box P3) cytokines from four cassettes. Immunization of mice groups was performed using produced plasmids intradermally. Specific IgG1 and IgG2 and IgA antibody titers produced in mice were confirmed by enzyme-linked immunosorbent assay (ELISA) in sera and intestine obtained four weeks after the last immunization. After being stimulated with a mixture of both anti-CD28 mAb and H. pylori lysate, frequencies of single Interferon-Gamma (IFN-gamma), single IL-17 and dual IFN-gamma/IL-17-secreting T-cells were documented using dual-color FluoroSpot. The kinetics of Th1, Th2 and Th17 in the immunized animals was determined by relative quantification of IL-17A, IL-22, IFN-gamma, IL-8, IL-2 and IL-4 specific mRNAs. Four weeks after bacterial challenge, quantitative colony count in the isolated and homogenized stomachs was utilized to assess the level of protective immunity among all groups. The results of immunologic assays showed that the highest cell-mediated immunity cytokines were produced in IL-17 receiving group in which the Treg responses were suppressed previously by the administration of the Foxp3 as an immunogen. In addition, potent clearance of Helicobacter pylori infection was seen in this group as well. CI - Copyright (c) 2019 Elsevier Ltd. All rights reserved. FAU - Nemattalab, Mehran AU - Nemattalab M AD - Department of Microbiology, Faculty of Medicine, Guilan University of Medical Sciences, Rasht, Iran. FAU - Shenagari, Mohammad AU - Shenagari M AD - Department of Microbiology, Faculty of Medicine, Guilan University of Medical Sciences, Rasht, Iran; Cellular and Molecular Research Center, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran. Electronic address: Shenagari@gums.ac.ir. FAU - Taheri, Mojtaba AU - Taheri M AD - Department of Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran. FAU - Mahjoob, Mohammad AU - Mahjoob M AD - Department of Microbiology, Faculty of Medicine, Guilan University of Medical Sciences, Rasht, Iran. FAU - Nazari Chamaki, Foroogh AU - Nazari Chamaki F AD - Faculty of Medicine, Guilan University of Medical Sciences, Rasht, Iran. FAU - Mojtahedi, Ali AU - Mojtahedi A AD - Department of Microbiology, Faculty of Medicine, Guilan University of Medical Sciences, Rasht, Iran; Cellular and Molecular Research Center, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran. FAU - Hasan-Alizadeh, Elham AU - Hasan-Alizadeh E AD - Faculty of Medicine, Guilan University of Medical Sciences, Rasht, Iran. FAU - Ashrafkhani, Babak AU - Ashrafkhani B AD - Faculty of Medicine, Guilan University of Medical Sciences, Rasht, Iran. FAU - Mousavi Niri, Neda AU - Mousavi Niri N AD - Department of Biotechnology, Faculty of Advanced Medical Sciences, Tehran Medical Branch, Islamic Azad University, Tehran, Iran. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20191016 PL - England TA - Cytokine JT - Cytokine JID - 9005353 RN - 0 (Adjuvants, Immunologic) RN - 0 (Foxa3 protein, mouse) RN - 0 (Immunoglobulin G) RN - 0 (Interleukin-17) RN - 0 (Interleukin-18) RN - 0 (Interleukin-2) RN - 0 (Interleukin-8) RN - 0 (Interleukins) RN - 0 (Recombinant Proteins) RN - 0 (Vaccines) RN - 135845-91-9 (Hepatocyte Nuclear Factor 3-gamma) RN - 207137-56-2 (Interleukin-4) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - *Adjuvants, Immunologic MH - Animals MH - Helicobacter Infections/*prevention & control MH - Helicobacter pylori/*immunology MH - Hepatocyte Nuclear Factor 3-gamma/immunology MH - Immunoglobulin G/blood MH - Interferon-gamma/blood/genetics/metabolism MH - Interleukin-17/*blood/genetics/metabolism MH - Interleukin-18/blood/genetics/metabolism MH - Interleukin-2/blood/genetics MH - Interleukin-4/blood/genetics MH - Interleukin-8/blood/genetics MH - Interleukins/blood/genetics/metabolism MH - Mice MH - Recombinant Proteins MH - T-Lymphocytes, Regulatory/immunology/*metabolism MH - Th1 Cells/immunology MH - Th17 Cells/immunology MH - Th2 Cells/immunology MH - Vaccines/immunology MH - Interleukin-22 OTO - NOTNLM OT - Helicobacter pylori OT - IL-17A OT - IL-18 OT - IL-22 OT - Treg OT - Vaccine EDAT- 2019/10/20 06:00 MHDA- 2021/07/27 06:00 CRDT- 2019/10/20 06:00 PHST- 2019/08/21 00:00 [received] PHST- 2019/09/15 00:00 [revised] PHST- 2019/09/25 00:00 [accepted] PHST- 2019/10/20 06:00 [pubmed] PHST- 2021/07/27 06:00 [medline] PHST- 2019/10/20 06:00 [entrez] AID - S1043-4666(19)30295-9 [pii] AID - 10.1016/j.cyto.2019.154866 [doi] PST - ppublish SO - Cytokine. 2020 Feb;126:154866. doi: 10.1016/j.cyto.2019.154866. Epub 2019 Oct 16.