Immunization with a SyntheticHelicobacter pyloriPeptide Induces Secretory IgA Antibodies and Protects Mice against Infection

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.

Review: Helicobacter: Inflammation, immunology, and vaccines

“…The vaccine efficacy of another peptide antigen (MVTLINNE), derived from an H pylori 50-52 kDa immunogenic protein, induced significant increased levels of splenic lymphoproliferation in mice. 33 Nevertheless, no significant differences in serum Th1 or Th2 cytokines were observed, nor was any evidence of protection against H pylori infection provided. 33 Ghasemi et al 34 hypothesized that the combination of multiple protective antigens may be more efficient than single antigenic preparations in inducing protective immune responses.…”

“…33 Nevertheless, no significant differences in serum Th1 or Th2 cytokines were observed, nor was any evidence of protection against H pylori infection provided. 33 Ghasemi et al 34 hypothesized that the combination of multiple protective antigens may be more efficient than single antigenic preparations in inducing protective immune responses. To address this hypothesis, they constructed a fusion protein (rFUVL) from the antigenic parts of H pylori flagellar hook-associated protein 2 (FliD), urease B subunit (UreB), VacA, and CagL.…”

“…31 Ning et al 32 identified two immunodominant epitopes within H pylori Lpp20 that were able to stimulate the proliferation of CD4 + T cells from H pylori-infected subjects. 33 Ghasemi et al 34 34 Moreover, vaccinated mice showed a mixed Th1/ Th2/Th17 response and antigen-specific IgG2a/IgG1 production. The vaccine efficacy of another peptide antigen (MVTLINNE), derived from an H pylori 50-52 kDa immunogenic protein, induced significant increased levels of splenic lymphoproliferation in mice.…”

Review ‐ Helicobacter, inflammation, immunology and vaccines

“…An H pylori peptide antigen with the sequence Met‐Val‐Thr‐Leu‐Ile‐Asn‐Asn‐Glu (MVTLINNE) was also used by Espinosa‐Ramos et al in prophylactic immunisation. This peptide protected 100% of the mice against H pylori infection, but the immune mechanisms remain to be identified 31 …”

Naturally secreted bacterial outer membrane vesicles: potential platform for a vaccine againstCampylobacter jejuni

“…To determine histological changes, histopathological analysis of ceca from experimental mice at day 7 post bacterial challenge was performed as per the method described elsewhere with slight modifications [121]. Briefly, the cecum was fixed in 10 % formal solution (prepared in PBS) for 48 h at RT.…”