Induction of mucosal immune responses against Helicobacter pylori infection after sublingual and intragastric route of immunization.
There is a current lack of effective mucosal vaccines against major gastroenteric pathogens and particularly against Helicobacter pylori, which causes a chronic infection that can lead to peptic ulcers and gastric cancer in a subpopulation of infected individuals. Mucosal CD4+T-cell responses have been shown to be essential for vaccine-induced protection against H. pylori infection. The current study addresses the influence of the adjuvant and site of mucosal immunization on early CD4+T-cell priming to H. pylori antigens. The vaccine formulation consisted of H. pylori lysate antigens and mucosal adjuvants, cholera toxin (CT) or a detoxified double-mutant heat-labile enterotoxin from Escherichia coli (dmLT), which were administered by either the sublingual or intragastric route. We report that in vitro, adjuvants CT and dmLT induce up-regulation of pro-inflammatory gene expression in purified dendritic cells and enhance the H. pylori-specific CD4+T-cell response including interleukin-17A (IL-17A), interferon-γ (IFN-γ) and tumour necrosis factor-α (TNF-α) secretion. In vivo, sublingual immunization led to an increased frequency of IL-17A+, IFN-γ+and TNF-α+secreting CD4+T cells in the cervical lymph nodes compared with in the mesenteric lymph nodes after intragastric immunization. Subsequently, IL-17A+cells were visualized in the stomach of sublingually immunized and challenged mice. In summary, our results suggest that addition of an adjuvant to the vaccine clearly activated dendritic cells, which in turn, enhanced CD4+T-cell cytokines IL-17A, IFN-γ and TNF-α responses, particularly in the cervical lymph nodes after sublingual vaccination.
Department of Microbiology & Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Louise
L
Sjökvist Ottsjö
Department of Microbiology & Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Frida
F
Jeverstam
Department of Microbiology & Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Linda
L
Yrlid
Department of Microbiology & Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Alexander U
AU
Wenzel
School of Science, RMIT University, Bundoora, Vic., Australia.
Anna K
AK
Walduck
Department of Microbiology & Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Sukanya
S
Raghavan
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000286:Administration, Sublingual; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D001427:Bacterial Toxins / Q000008:administration & dosage; D001428:Bacterial Vaccines / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000008:administration & dosage; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D004768:Enterotoxins / Q000008:administration & dosage; D029968:Escherichia coli Proteins / Q000008:administration & dosage; D005260:Female; D016481:Helicobacter Infections / Q000276:immunology*; D016480:Helicobacter pylori / Q000276:immunology*; D018928:Immunity, Mucosal; D018836:Inflammation Mediators / Q000378:metabolism; D007441:Intubation, Gastrointestinal; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL
D000276:Adjuvants, Immunologic; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D001428:Bacterial Vaccines; D016207:Cytokines; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D018836:Inflammation Mediators; D002772:Cholera Toxin; C027538:heat-labile enterotoxin, E coli
T cells; cytokines; dendritic cells; mucosa; vaccination
J Immunol. 2004 Apr 15;172(8):5024-33
15067084
Vaccine. 2011 Feb 1;29(6):1235-41
21147129
Helicobacter. 2011 Jun;16(3):169-78
21585602
J Immunol. 2009 Jun 1;182(11):6851-60
19454681
Cytokine. 2011 Apr;54(1):1-5
21239178
Vaccine. 2007 Dec 12;25(51):8598-610
17996991
J Immunol. 2011 Oct 1;187(7):3641-52
21880985
Eur J Immunol. 2010 Oct;40(10):2778-90
21038469
Immunol Rev. 2010 Mar;234(1):259-67
20193024
PLoS One. 2016 Feb 11;11(2):e0148514
26867135
PLoS One. 2015 Jul 13;10(7):e0131444
26168305
Mediators Inflamm. 2011;2011:296069
21765615
Infect Immun. 2013 May;81(5):1532-40
23439305
Helicobacter. 2008 Apr;13(2):94-102
18321299
Vaccine. 2014 Dec 12;32(52):7077-84
25444830
Hum Vaccin. 2011 Jan 1;7(1):110-4
21263223
Gastroenterology. 2009 Jun;136(7):2237-2246.e1
19272385
Immunol Rev. 2008 Dec;226:160-71
19161423
Vaccine. 2010 Aug 2;28(34):5582-90
20600505
Clin Vaccine Immunol. 2011 Apr;18(4):546-51
21288994
Gastroenterology. 2009 Jan;136(1):247-56
18948106
Pathog Dis. 2013 Feb;67(1):46-53
23620119
Curr Opin Immunol. 2011 Jun;23(3):414-20
21511452
Mucosal Immunol. 2008 Jan;1(1):59-67
19079161
Eur J Immunol. 1992 Sep;22(9):2277-81
1381311
Infect Immun. 2011 Feb;79(2):879-86
21078851
Vaccine. 2016 Apr 19;34(18):2121-8
26973069
J Immunol. 1989 Jan 1;142(1):20-7
2783324
Infect Immun. 2010 Oct;78(10):4251-60
20696831
Vaccine. 2010 Feb 3;28(5):1404-11
19897067
Cancer Res. 2000 Jun 15;60(12):3239-46
10866317
Infect Immun. 2003 Jan;71(1):504-9
12496201