Effects of a Th1- versus a Th2-biased immune response in protection against Helicobacter pylori challenge in mice

Abstract

The roles that T helper type 1 (Th1) and T helper type 2 (Th2) H. pylori specific immune responses play in protection from H. pylori challenge are poorly understood. It is expected that Th2 immune responses are required for protection against extracellular bacteria, such as H. pylori. However, recent studies have suggested that Th1 immunity is required for protection. The mechanisms by which this might occur are unknown. Our goal in this study was to more clearly define the effects of a Th1 vs. a Th2 promoting H. pylori vaccine on immunity and protection. Therefore, we tested a Th1 vaccine consisting of an H. pylori sonicate and CpG oligonucleotides (CpG) and a Th2 vaccine consisting of a lipopolysaccharide (LPS) depleted H. pylori sonicate combined with cholera toxin (CT). We demonstrate that although the Th2 promoting vaccine induced stronger systemic and local immune responses, only the Th1 promoting vaccine was protective.

Selection of Adjuvants for Enhanced Vaccine Potency

“…However, the actual protection offered by these two pathways is still not so clear-cut. For example, it is expected that Th2 immune responses are required for protection against extracellular bacteria, such as H. pylori but only a Th1-promoting vaccine (H. pylori sonicate + CpG) showed protection in mice [17]. Similar results were obtained where a strong Th2-inducing protein vaccine was not as effective in the protection of mice from virus challenge [18].…”

Frequency of virulence factors in Helicobacter pylori-infected patients with gastritis

“…This bacterium induces gastritis, peptic ulcer and is associated with gastric carcinoma [1,2]. The clinical outcome of H. pylori infection has been associated with bacterial virulence factors, host gastric mucosal factors, and the environment [3].…”

Oral Immunization with Recombinant Mycobacterium smegmatis Expressing the Outer Membrane Protein 26-Kilodalton Antigen Confers Prophylactic Protection against Helicobacter pylori Infection

“…Several earlier studies have documented that a CD4 ϩ T cell-mediated IFN-␥ response is not only essential for vaccine-induced protection, but also involved in the induction of gastric inflammation caused by H. pylori infection (19,26). It has been proposed that Th1 immune responses are crucial for H. pylori-specific protective immunity (1,30). Oral inoculation of the present vaccine candidate was found to induce a prominent Th1 response characterized by increased expression of Th1 cytokines (IFN-␥ and IL-2) and high IgG2a serum titers.…”