Review: Helicobacter: Inflammation, immunology, and vaccines

Abstract

Chronic inflammation induced by Helicobacter pylori infection is a critical factor in the development of peptic ulcer disease and gastric cancer. Central to this inflammation is the initiation of pro‐inflammatory signaling cascades within epithelial cells, in particular those mediated by two sensors of bacterial cell wall components, nucleotide‐binding oligomerization domain‐containing protein 1 (NOD1) and alpha‐protein kinase 1 (ALPK1). H pylori is, however, also highly adept at mitigating inflammation in the host, thereby restricting tissue damage and favoring bacterial persistence. H pylori modulates host immune responses by altering cytokine signaling in epithelial and myeloid cells, which results in increased proliferation of regulatory T cells and downregulation of effector T‐cell responses. H pylori vacuolating cytotoxin A (VacA) has been shown to play an important role in the dampening of immune responses and induction of immune tolerance capable of protecting against asthma. It is also possible to generate protective immune responses by immunization with various H pylori antigens or their epitopes, in combination with an adjuvant, though this for now has only been shown in mouse models. Novel non‐toxic adjuvants, consisting of modified bacterial enterotoxins or nanoparticles, have recently been developed that may not only enhance vaccine efficacy, but also help translate candidate vaccines to the clinic. This review will summarize the main discoveries in the past year regarding host immune responses to H pylori infection, as well as the design of new vaccine approaches against this infection.

Role of Helicobacters in Neuropsychiatric Disease: A Systematic Review in Idiopathic Parkinsonism

“…Anti-CagA cross-reacts with peptides on platelets: these antibodies decline following eradication when platelet counts improve. VacA has an important role in dampening immune responses and in induction of immune tolerance early in life [ 90 ]. It shifts T-cell responses towards regulatory rather than effector functions.…”

Systematic Analysis of Monoterpenes: Advances and Challenges in the Treatment of Peptic Ulcer Diseases

“…However, when long-term acid suppression treatment is needed, side-effects such as hypergastrinemia, pneumonia, bacterial overgrowth in the small intestine, and infection with Clostridium difficile may occur, even with the classic anti-ulcer drugs such as PPIs or even with vonoprazan [28,29]. A new vaccine for primary prevention against H. pylori is currently under development [30].…”

“…However, when long-term acid suppression treatment is needed, side-effects such as hypergastrinemia, pneumonia, bacterial overgrowth in the small intestine, and infection with Clostridium difficile may occur, even with the classic anti-ulcer drugs such as PPIs or even with vonoprazan [28,29]. A new vaccine for primary prevention against H. pylori is currently under development [30].Due to the decrease in the efficacy of first-line treatments, increase of side-effects, and worldwide reports of H. pylori's resistance to antibiotics, new approaches are needed to manage this problematic infection; thus, efforts are being directed towards the development and delivery of new anti-H. pylori drugs [31]. Natural products, especially compounds derived from medicinal plants, have been sought as a source of new medicine, due to the great variety of chemical structures and structural modifications [32][33][34][35][36].…”

Outer Membrane Vesicles of Helicobacter pylori 7.13 as Adjuvants Promote Protective Efficacy Against Helicobacter pylori Infection

“…H. pylori can evade the host immune response via altering cytokine signaling in epithelial and myeloid cells as well as releasing vacuolating cytotoxin A (VacA). Some vaccines are unable to generate sufficient immune responses to qualify for clinical trials (Altobelli et al, 2019;Lehours and Ferrero, 2019). Therefore, more powerful antigens and immunomodulators are needed to invoke a satisfactory immune response (Sutton and Chionh, 2013).…”

“…While classical adjuvants, such as potassium alum, have been frequently used, subsequent studies have generated novel candidates (Arzeno Carranza, 1950;Sjokvist Ottsjo et al, 2013;Liu et al, 2017;Longet et al, 2019). For anti-H. pylori vaccines, cholera toxin (CT) and Escherichia coli heat-labile enterotoxin (LT) are widely used as adjuvants to boost the efficacy of mucosal vaccines in mice (Lehours and Ferrero, 2019). However, they both exhibit enterotoxicity, which limit their clinical applications.…”