Sublingual immunization protects against Helicobacter pylori infection and induces T and B cell responses in the stomach.
Sublingual (SL) immunization has been described as an effective novel way to induce mucosal immune responses in the respiratory and genital tracts. We examined the potential of SL immunization against Helicobacter pylori to stimulate immune responses in the gastrointestinal mucosa and protect against H. pylori infection. Mice received two SL immunizations with H. pylori lysate antigens and cholera toxin as an adjuvant, and after challenge with live H. pylori bacteria, their immune responses and protection were evaluated, as were immune responses prior to challenge. SL immunization induced enhanced proliferative responses to H. pylori antigens in cervicomandibular lymph nodes and provided at least the same level of immune responses and protection as corresponding intragastric immunization. Protection in SL-immunized mice was associated with strong H. pylori-specific serum IgG and IgA antibody responses in the stomach and intestine, with strong proliferation and gamma interferon (IFN-γ) and interleukin-17 (IL-17) production by spleen and mesenteric lymph node T cells stimulated with H. pylori antigens in vitro, and with increased IFN-γ and IL-17 gene expression in the stomach compared to levels in infected unimmunized mice. Immunohistochemical studies showed enhanced infiltration of CD4(+) T cells and CD19(+) B cells into the H. pylori-infected stomach mucosa of SL-immunized but not unimmunized H. pylori-infected mice, which coincided with increased expression of the mucosal addressin cell adhesion molecule (MAdCAM-1) and T and B cell-attracting chemokines CXCL10 and CCL28. We conclude that, in mice, SL immunization can effectively induce protection against H. pylori infection in association with strong T and B cell infiltration into the stomach.
Raghavan
Sukanya
S
University of Gothenburg Vaccine Research Institute, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden. sukanya.raghavan@microbio.gu.se
Ostberg
Anna Karin
AK
Flach
Carl-Fredrik
CF
Ekman
Annelie
A
Blomquist
Margareta
M
Czerkinsky
Cecil
C
Holmgren
Jan
J
D000286:Administration, Sublingual; D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D001428:Bacterial Vaccines / Q000008:administration & dosage*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D016481:Helicobacter Infections / Q000517:prevention & control*; D016480:Helicobacter pylori / Q000276:immunology*; D008198:Lymph Nodes; D051379:Mice; D008810:Mice, Inbred C57BL; D009088:Mucoproteins; D013047:Specific Pathogen-Free Organisms; D013270:Stomach / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000502:physiology*; D006377:T-Lymphocytes, Helper-Inducer
D001428:Bacterial Vaccines; D015815:Cell Adhesion Molecules; C489082:Madcam1 protein, mouse; D009088:Mucoproteins