Vaccine‐Mediated Protection against Helicobacter pylori is not Associated with Increased Salivary Cytokine or Mucin Expression

Abstract

The development of an effective vaccine against Helicobacter pylori is impeded by the inability to reliably produce sterilizing immunity and our lack of knowledge regarding mechanisms of protective immunity against this pathogen. It has previously been described that salivary glands are essential for vaccine-mediated protection against H.pylori, but the mechanism responsible for this effect has not been identified. In this study we tested the hypothesis that vaccines reduce H.pylori colonization by inducing an immune-mediated change in salivary gland mucin secretion. Sublingual and submandibular salivary glands were removed from untreated mice, from mice infected with H.pylori and from mice vaccinated against H.pylori then challenged with live bacteria. Cytokine levels in these salivary glands were quantified by ELISA, and salivary mucins were quantified by real-time PCR. Salivary antibody responses were determined by Western blot. Vaccine-mediated protection against H.pylori did not produce any evidence of a positive increase in either salivary cytokine or mucin levels. In fact, many cytokines were significantly reduced in the vaccinated/challenged mice, including IL-17A, IL-10, IL-1ß, as well as the mucin Muc10. These decreases were associated with an increase in total protein content within the salivary glands of vaccinated mice which appeared to be the result of increased IgA production. While this study showed that vaccination increased salivary IgA levels, previous studies have demonstrated that antibodies do not play a critical role in protection against H.pylori that is induced by current vaccine formulations and regimes. The effector mechanism of protective immunity induced by vaccination of mice did not involve immune changes within the salivary glands, nor increased production of salivary mucins.