Helicobacter pylori CagA: From Pathogenic Mechanisms to Its Use as an Anti-Cancer Vaccine

Abstract

Helicobacter pylori colonizes the gastric mucosa of more than 50% of the human population, causing chronic inflammation, which however is largely asymptomatic. Nevertheless, H. pylori-infected subjects can develop chronic gastritis, peptic ulcer, gastric mucosa-associated lymphoid tissue lymphoma, and gastric cancer. Chronic exposure to the pathogen and its ability to induce epithelial to mesenchymal transition (EMT) through the injection of cytotoxin-associated gene A into gastric epithelial cells may be key triggers of carcinogenesis. By deregulating cell–cell and cell–matrix interactions as well as DNA methylation, histone modifications, expression of micro RNAs, and resistance to apoptosis, EMT can actively contribute to early stages of the cancer formation. Host response to the infection significantly contributes to disease development and the concomitance of particular genotypes of both pathogen and host may turn into the most severe outcomes. T regulatory cells (Treg) have been recently demonstrated to play an important role in H. pylori-related disease development and at the same time the Treg-induced tolerance has been proposed as a possible mechanism that leads to less severe disease. Efficacy of antibiotic therapies of H. pylori infection has significantly dropped. Unfortunately, no vaccine against H. pylori is currently licensed, and protective immunity mechanisms against H. pylori are only partially understood. In spite of promising results obtained in animal models of infection with a number of vaccine candidates, few clinical trials have been conducted so far and with no satisfactory outcomes. However, prophylactic vaccination may be the only means to efficiently prevent H. pylori-associated cancers.

The Human Antimicrobial Protein Calgranulin C Participates in Control of Helicobacter pylori Growth and Regulation of Virulence

“…The cag T4SS is a macromolecular nanomachine responsible for translocating substrates, including peptidoglycan and the oncogenic effector molecule CagA, into host epithelial cells (6). The translocation activity of the cag T4SS leads to multiple consequences in host cell biology, including cytoskeletal rearrangements, induction of carcinogenic cell-signaling cascades, alteration of DNA methylation, perturbation of metal homeostasis, and secretion of proinflammatory molecules (6)(7)(8)(9).…”

The Place of Helicobacter pylori in Human Health; Where is it Standing in the Balance Between Harm and Benefit?

“…Ayrıca rekombinant CagA, VacA ve HP-NAP proteinlerini içeren faz I klinik aşı çalışmaları mevcuttur. Fakat günümüzde halen H. pylori'ye karşı lisanslı bir aşı yoktur (38) .…”

Claudins, Inflammation and Epithelial-Mesenchymal Transition in Gastric Tissue

“…Interleukin 8 participation in oncogenesis has been clearly established [121], therefore in the frame of all these considerations it is clear that the sole prophylaxis of H. pylori infection with antibiotic therapy might not be sufficient to avoid gastric carcinogenesis [122] especially when pre-malignant lesions are already present. Serious efforts to develop an H. pylori vaccine are underway but information regarding possible host advantages in the host life is emerging [123,124].…”