Therapeutic Vaccination againstHelicobacter pyloriin the Beagle Dog Experimental Model: Safety, Immunogenicity, and Efficacy

Abstract

Helicobacter pylori is a gram-negative bacterium that colonizes the human gastric mucosa causing gastritis and peptic ulcer and increasing the risk of gastric cancer. The efficacy of current antibiotic-based therapies can be limited by problems of patient compliance and increasing antibiotic resistance; the vaccine approach can overcome these limits. The present study describes the therapeutic vaccination of experimentally H. pyloriinfected beagle dogs, an animal model that reproduces several aspects of the human infection with H. pylori. The vaccine consisted of three recombinant H. pylori antigens, CagA, VacA, and NAP, formulated at different doses (10, 25, or 50 g each) with alum and administered intramuscularly either weekly or monthly. No adverse effects were observed after vaccination and a good immunoglobulin G response was generated against each of the three antigens. Bacterial colonization and gastritis were decreased after the completion of the vaccination cycle, especially in the case of the monthly immunization schedule. In conclusion, therapeutic vaccination in the beagle dog model was safe and immunogenic and was able to limit H. pylori colonization and the related gastric pathology.Helicobacter pylori is a spiral-shaped, gram-negative bacterium that infects the stomach of Ͼ50% of the population worldwide, with higher prevalence in the developing countries. H. pylori induces chronic inflammation of the stomach mucosa, causing chronic gastritis and peptic ulcer (9, 33); moreover, H. pylori infection is related to gastric mucosa-associated lymphoid tissue lymphoma (4) and to an increased risk of gastric cancer (36), as also proved in animal models (13,38).Current therapies, based on one antisecretory agent plus antibiotics, although effective in 80 to 90% of cases, face problems of patient compliance, increasing antibiotic resistance, and possible recurrence or reinfection; in spite of continuous effort to improve these treatments, no major breakthroughs have been achieved in the most recent years (30).To overcome the limits of antibiotic-based therapies, the vaccine approach has been undertaken since the last decade, leading us to identify some relevant bacterial antigens as candidates for vaccines (2). On the other hand, animal models of H. pylori infection have been developed to study the interaction between the bacterium and the host, the mechanisms of immune response to either infection or vaccination, and to determine the efficacy of both prophylactic and therapeutic vaccination (2,17,26,34). Among these animal models, that of the beagle dog reproduces several aspects of the human infection with H. pylori. In fact, in the beagle dog model, intragastric administration of H. pylori results in a long-term chronic infection, characterized by gastritis, epithelial alterations, superficial erosions, and the appearance of macroscopic follicles in the gastric mucosa, mainly in the antral region of the stomach (28,29).Most of the examples of vaccination against H. pylori in animal models reported in the...

The Campylobacter jejuni Dps Homologue Is Important forIn VitroBiofilm Formation and Cecal Colonization of Poultry and May Serve as a Protective Antigen for Vaccination

“…Given the colonization reduction observed in the dps mutant, the surface localization of the protein, and the success obtained with a Dps homologue as a vaccine to prevent peptic ulcers in humans (20,28,30), preliminary testing of Dps as a potential vaccine antigen for the reduction of C. jejuni in broiler chickens was performed. Although subcutaneous vaccination of poultry with recombinantly expressed Dps generated good serum responses compared to those for unvaccinated controls (data not shown), there was no impact on cecal colonization.…”

Helicobacter pyloriPersistence: an Overview of Interactions betweenH. pyloriand Host Immune Defenses

“…Both prophylactic H. pylori immunization (to prevent future infection) and therapeutic immunization (to eradicate an established infection) have been successfully accomplished in animal models (50,106,142,195).…”

Complexomics Study of Two Helicobacter pylori Strains of Two Pathological Origins

“…Among the antigenic proteins reported in H. pylori, most correspond to housekeeping enzymes rather than to antigens associated with the cell envelope (48). Attempts were made to develop a vaccine against H. pylori with candidate antigens such as urease (181), catalase (182), and CagA and VacA cytotoxins (183). However, none of these vaccines showed satisfactory protection against the infection.…”