Chitosan as an adjuvant for a Helicobacter pylori therapeutic vaccine

Abstract

The aim of the present study was to delineate the therapeutic effect of a Helicobacter pylori vaccine with chitosan as an adjuvant, as well as to identify the potential mechanism against H. pylori infection when compared with an H. pylori vaccine, with cholera toxin (CT) as an adjuvant. Mice were first infected with H. pylori and, following the establishment of an effective infection model, were vaccinated using an H. pylori protein vaccine with chitosan as an adjuvant. Levels of H. pylori colonization, H. pylori-specific antibodies and cytokines were determined by enzyme-linked immunosorbent assay. The TLR4 and Foxp3 mRNA and protein levels were determined by reverse transcription polymerase chain reaction and immunohistochemistry, respectively. It was identified that the H. pylori elimination rate of the therapeutic vaccine with chitosan as an adjuvant (58.33%) was greater than the therapeutic vaccine with CT as an adjuvant (45.45%). The therapeutic H. pylori vaccine with chitosan as an adjuvant induced significantly greater antibody and cytokine levels when compared with the control groups. Notably, the IL-10 and IL-4 levels in the groups with chitosan as an adjuvant to the H. pylori vaccine were significantly greater than those in the groups with CT as an adjuvant. The mRNA expression levels of TLR4 and Foxp3 were significantly elevated in the mice that were vaccinated with chitosan as an adjuvant to the H. pylori vaccine, particularly in mice where the H. pylori infection had been eradicated. The H. pylori vaccine with chitosan as an adjuvant effectively increased the H. pylori elimination rate, the humoral immune response and the Th1/Th2 cell immune reaction; in addition, the therapeutic H. pylori vaccine regulated the Th1 and Th2 response. The significantly increased TLR4 expression and decreased CD4+CD25+Foxp3+Treg cell number contributed to the immune clearance of the H. pylori infection. Thus, the present findings demonstrate that in mice the H. pylori vaccine with chitosan as an adjuvant exerts an equivalent immunotherapeutic effect on H. pylori infection when compared with the H. pylori vaccine with CT as an adjuvant.

Overexpression of Tim-3 reduces Helicobacter pylori-associated inflammation through TLR4/NFκB signaling in vitro

“…These results suggest that Tim-3 inhibited the activation of macrophages by negatively regulating the TLR4 signaling pathway. A previous study from this group (26) demonstrated that blocking Tim-3 with an inhibitory antibody upregulated TLR4 and MyD88 expression, promoted NF-κB activation, decreased the number of CD4 + CD25 + Foxp3 + Treg cells, and upregulated Th1 immune responses, resulting in intensified inflammation of the gastric mucosa of H. pylori-infected mice. Frisancho et al (11) reported that, in a mouse model of inflammatory heart disease, blocking Tim-3 significantly increases TLR4 expression and cardiac inflammation, indicating that Tim-3 is a negative regulator of the TLR4 signaling pathway.…”

Immunologic properties and therapeutic efficacy of a multivalent epitope‐based vaccine against four Helicobacter pylori adhesins (urease, Lpp20, HpaA, and CagL) in Mongolian gerbils

“…Furthermore, natural polysaccharides as adjuvants are paving their way as a safe alternative, such as chitosan and Lycium barbarum polysaccharides (LBP). Earlier studies have demonstrated that H. pylori vaccine with chitosan as an adjuvant can protect against H. pylori infection and induce mixed Th‐cell responses . In addition, previous studies have shown that Lycium barbarum polysaccharides (LBP) can enhance T cell‐dependent antibody responses as an adjuvant .…”

Novel application of trimethyl chitosan as an adjuvant in vaccine delivery

“…30 Ovalbumin (OVA)/granulocyte-macrophage colony-stimulating factor-loaded chitosan NPs performed equivalently to IFA and CFA in the generation of OVA-specific antibody titer as well as CD4 + and CD8 + INF-γ + T cells. 31 Chitosan has been tested with hepatitis B virus surface antigen (HBsAg) 32 diphtheria toxin, Mycobacterium tuberculosis CFP10-TB10.4 fusion protein, 33 inactivated NIBRG-14 (H5N1) subunit antigen against influenza A, virus-like particles against norovirus, 34 against poliovirus, 35 against influenza A (H7N9, H9N2, H1N1, and H5N1) virus infection, [36][37][38] and against Helicobacter pylori 39 and has proved its potency as a successful adjuvant against these diseases. Gordon et al demonstrated that thermosensitive chitosan hydrogels possess higher ability to stimulate both humoral-mediated immunity and CMI, in addition to a slow and controlled in vitro release of antigen, compared to chitosan NPs, liposomes, and lipid-based cubosomes.…”