Protective immunity enhanced Salmonella vaccine vectors delivering Helicobacter pylori antigens reduce H. pylori stomach colonization in mice

Abstract

<i>Helicobacter pylori</i> is a major cause of gastric mucosal inflammation, peptic ulcers, and gastric cancer. Emerging antimicrobial-resistant <i>H. pylori</i> has hampered the effective eradication of frequent chronic infections. Moreover, a safe vaccine is highly demanded due to the absence of effective vaccines against <i>H. pylori</i>. In this study, we employed a new innovative Protective Immunity Enhanced <i>Salmonella</i> Vaccine (PIESV) vector strain to deliver and express multiple <i>H. pylori</i> antigen genes. Immunization of mice with our vaccine delivering the HpaA, Hp-NAP, UreA and UreB antigens, provided sterile protection against <i>H. pylori</i> SS1 infection in 7 out of 10 tested mice. In comparison to the control groups that had received PBS or a PIESV carrying an empty vector, immunized mice exhibited specific and significant cellular recall responses and antigen-specific serum IgG1, IgG2c, total IgG and gastric IgA antibody titers. In conclusion, an improved <i>S.</i> Typhimurium-based live vaccine delivering four antigens shows promise as a safe and effective vaccine against <i>H. pylori</i> infection.