Induction of mucosal immune responses against Helicobacter pylori infection after sublingual and intragastric route of immunization

Abstract

SummaryThere 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 proinflammatory gene expression in purified dendritic cells and enhance the H. pylori-specific CD4 + T-cell response including interleukin-17A (IL-

The frequency of circulating integrin α4β7+ cells correlates with protection against Helicobacter pylori infection in immunized mice

“…Thus, we believe that the mobilization of neutrophils in blood particularly after SL vaccination might play a role in the polarization of CD4 + T‐cell responses to Th17 responses in the draining lymph nodes. Indeed, we have observed a significantly higher frequency of IL‐17A + cells in the stomach after infection with H pylori in sublingually immunized mice compared with intragastrically immunized mice . We also observed an increase in frequency of CD11b + Ly6G − inflammatory monocytes in the circulation after vaccination particularly after IG route of immunization in accordance with the study by Moyat et al Furthermore, we have previously reported the dependence of IFNγ on the protective immune response after IG immunization, and thus, the CD11b + Ly6G‐ inflammatory monocytes activated after IG route of vaccination might play a role in the polarization of the CD4 + T‐cell response to a Th1 phenotype .…”

“…Protection in immunized mice only correlated with high frequency of CD4 + α4β7 + cells in the circulation but not with the frequency of neutrophils, inflammatory monocytes or memory CD4 + CD62L − T cells (both SL and IG). Furthermore, in accordance with our previous studies, we also confirmed significantly lower bacterial colonization rates in sublingually compared to intragastrically immunized mice . Altogether, the data presented in the current study will be useful for the design and evaluation of a H pylori vaccine in clinical trials in high‐risk H pylori ‐infected individuals/patients.…”

Helicobacter: Inflammation, immunology and vaccines

“…Several groups investigated Helicobacter vaccines using mouse models, however, very few tested their protective efficacy. The most commonly investigated vaccine antigens were urease B, neuraminyllactose‐binding hemagglutinin (HpaA), and H. pylori whole cells or lysates …”

“…Several different adjuvants were used in the published studies, but as in previous years, the most common was cholera toxin B subunit . Bacteria expressing H. pylori antigens, including Lactococcus lactis, Vibrio cholerae, and Bacillus subtilis, were tested as recombinant vaccine vehicles.…”

“…Bacteria expressing H. pylori antigens, including Lactococcus lactis, Vibrio cholerae, and Bacillus subtilis, were tested as recombinant vaccine vehicles. Oral administration of the vaccine was most common, but one study showed a stronger cellular immune response to H. pylori vaccine administered via the sublingual route . Moyat et al .…”