Developing a potent vaccine against Helicobacter pylori: critical considerations and challenges

Abstract

Helicobacter pylori (H. pylori) is closely associated with gastric cancer and peptic ulcers. The effectiveness of antibiotic treatment against H. pylori is diminished by the emergence of drug-resistant strains, side effects, high cost and reinfections. Given the circumstances, it is imperative to develop a potent vaccination targeting H. pylori. Understanding H. pylori's pathogenicity and the host's immune response is essential to developing a vaccine. Furthermore, vaccine evaluation necessitates the careful selection of design formulation. This review article aims to provide a concise overview of the considerations involved in selecting the optimal antigen, adjuvant, vaccine delivery system and laboratory animal model for vaccine formulation. Furthermore, we will discuss some significant obstacles in the realm of developing a potent vaccination against H. pylori.

Keywords: Helicobacter pylori vaccines; adjuvants; animal models; antigens; delivery system.

Figure 1.

Schematic representation of the host immune system’s reactions to the Helicobacter pylori infection in the stomach. The first inflammation eradicates the bacteria and inhibits its dissemination. Capillary wall cells generate chemical mediators that infiltrate white blood cells at the site of injury during inflammation. As a result, neutrophils and monocytes in the blood are rejected. Dendritic cells, macrophages, neutrophils, lymphocytes and endothelium activate simple CD4⁺ T cells and trigger antigen-specific responses in Th1 and Th17 cells. Th1 cells produce IFN-γ and regulate cellular immunity, whereas Th17 cells produce IL-17. IL-12 and IL-23 are also present in H. pylori-stimulated macrophages. A T-reg regulatory cellular response is also observed, which enhances immunity while suppressing Th1- and Th17-induced immunity by generating IL-10 and TGF-β.

Figure 2.

Most effective antigens and various types of vaccines used in vaccine development against Helicobacter pylori.

Figure 3.

Overview of the function of vaccines and adjuvants. Antigenic proteins in vaccines, called pathogen-related molecular patterns (PAMPs), are presented to antigen-presenting cells (APCs) and are identified by their pattern recognition receptors (PRRs), such as toll-like receptors, at their surface. Adjuvants often act as PAMPs, which are identified by the PRR of the innate immune system. In the absence of adjuvants, mucosal delivery of vaccine antigens may result in T and B cell tolerance rather than effective immunization. Once identified, they are processed and placed on the major histocompatibility complex proteins (MHC-I or MHC-II) and are delivered to T cells native CD4⁺ that stimulate cellular and humoral immune responses. This stimulation leads to the production of antibodies in the humoral immune system and cytokines in the cellular immune system.