The Current Status of Helicobacter pylori Vaccines: A Review

Abstract

Helicobacter pylori, a Gram-negative flagellate bacterium that infects the stomach of more than half of the global population, is regarded as the leading cause of chronic gastritis, peptic ulcer disease, and even gastric adenocarcinoma in some individuals. Although the bacterium induces strong humoral and cellular immune responses, it can persist in the host for decades. It has several virulence factors, some of them having vaccine potential as judged by immunoproteomic analysis. A few vaccination studies involving a small number of infected or uninfected humans with various H. pylori formulations such as the recombinant urease, killed whole cells, and live Salmonella vectors presenting the subunit antigens have not provided satisfactory results. One trial that used the recombinant H. pylori urease coadministered with native Escherichia coli enterotoxin (LT) demonstrated a reduction of H. pylori load in infected participants. Although extensive studies in the mouse model have demonstrated the feasibility of both therapeutic and prophylactic immunizations, the mechanism of vaccine-induced protection is poorly understood as several factors such as immunoglobulin and various cytokines do not contribute to protection. Transcriptome analyses in mice have indicated the role of nonclassical immune factors in vaccine-induced protection. The role of regulatory T cells in the persistence of H. pylori infection has also been suggested. A recently developed experimental H. pylori infection model in humans may be used for testing several new adjuvants and vaccine delivery systems that have been currently obtained. The use of vaccines with appropriate immunogens, routes of immunization, and adjuvants along with a better understanding of the mechanism of immune protection may provide more favorable results.

Frequency of H. pylori Antibodies among Patients with Gastrointestinal Symptoms Attending Khartoum Teaching Hospital- Sudan

“…The present study results showed insignificant correlation between age and H. pylori antibodies, this was similar to study done in Iran by Alavi and others in 2010 [24], but it differ from Kabir, (2007) in Sweden who reported that the percentage of infected people increase with age [25]. Also Forman and Burley in 2006, stated that the prevalence of H. pylori infections increase, with age [26].…”

Impact of Microbial Infections on the Human Epigenome and Carcinogenesis

“…One such therapeutic effect is the reversal of methylation of E-cadherin induced by H. pylori in the stomach, and consequently reduction in the risk of cancer development [96,97]. A further option would be vaccines against the bacterial strain in question, such as investigated again for H. pylori [98], but not clinically effective as yet.…”

A role for altered phagosome maturation in the long-term persistence ofHelicobacter pyloriinfection

“…However, since it is possible to elicit protective immunity in mice that lack B cells (53, 137) and since H. pylori infection is not cleared in humans without antibiotic intervention, the humoral immune response has been considered to be an indication of infection, rather than a marker of protection (72). Furthermore, on the basis of evidence obtained using a B cell-deficient mouse model, H. pylorispecific antibodies may actually enhance colonization (3,72).…”

“…H. pylori has a series of mechanisms that enable it to evade cell-mediated and cell-free immune killing. While the bacterium has been shown to be efficiently coated by antibodies in vitro and in vivo (72,141), H. pylori also avoids antibody-dependent cell-mediated cytotoxicity, complement fixation, and the agglutinating effects of antibodies. Furthermore, the effector cells recruited to the site of infection are unable to clear the bacterium by the array of antioxidant compounds that can be deployed by H. pylori and by disturbed phagosome maturation.…”