Abstract

Helicobacter pylori is a spiral Gram-negative bacterium associated with inflammation of the gastric mucosa, peptic ulcer, and gastric adenocarcinoma, whose treatment has failed due to antibiotic resistance and side effects. Furthermore, because there are no vaccines effective against H. pylori, an appropriate vaccine design targeting conserved/essential genes must be identified. In the present study, a H. pylori 50–52 kDa immunogen-derived peptide antigen with the sequence Met-Val-Thr-Leu-Ile-Asn-Asn-Glu (MVTLINNE) was used to immunize against H. pylori infection. For this, mice received an intraperitoneal injection of 100 μg of H. pylori peptide on the first week, followed by two weekly subcutaneous reinforcements and further 109 bacteria administration in the drinking water for 3 weeks. Thymic cells proliferative responses to concanavalin A, serum levels of IL-2, IL-4, IL-6, IL-10, IL-17, IFN-γ, and TNF-α cytokines, and IgG1, IgG2a, IgG2b, IgG3 IgM, and IgA immunoglobulins were evaluated. Significant (p < 0.05) increases on lymphoproliferation and spleen weights after immunization were observed. In contrast, infection significantly (p < 0.05) decreased lymphoproliferation, which was recovered in immunized mice. In addition, levels of serum TH1 and TH2 cytokines were not altered after immunization, except for the significant increase in IL-6 production in immunized and/or infected animals. Moreover, immunization correlated with plasma secretory IgA and IgG, whereas infection alone only elicited IgM antibodies. Peptide immunization protected 100% of mice against virulent H. pylori. MVTLINNE peptide deserves further research as an approach to the prophylaxis of H. pylori infection.

Highlights

  • H. pylori is a Gram-negative spiral-shaped bacterium that represents the main factor for the development of human chronic gastritis, duodenal ulcer, and gastric adenocarcinoma [1,2,3]

  • Effect of Immunization on ymic Lymphocyte Proliferation. ymus cell lymphocytes from immunized, immunized plus infected, infected, and control animals were incubated in the presence or absence of concanavalin A (Con A) or MVTLINNE peptide, and lymphoproliferative responses determined, as explained above

  • It is estimated that 50% of the world population has been infected by H. pylori, a disease that in the early stages is not considered deadly, in the long term, it leads to more serious diseases, such as cancer

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Summary

Introduction

H. pylori is a Gram-negative spiral-shaped bacterium that represents the main factor for the development of human chronic gastritis, duodenal ulcer, and gastric adenocarcinoma [1,2,3]. Despite the decrease in the incidence of gastric carcinoma due to H. pylori in recent years, this disease is still the most common cause of death from cancer worldwide. It is the fourth cause of cancer cases per year, according to a 2000 report, with 945,000 new cases [1]. Clarithromycin resistance has recently been reported in 26%, 27.2%, and 25% of patients infected by H. pylori in France, Spain, and Italy, respectively [9]. There has been an increasing interest in the development of vaccines as a prophylaxis to H. pylori infection [12]

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