Helicobacter pylori is a leading cause of gastric mucosal inflammation, peptic ulcers, and gastric adenocarcinoma. Emerging antimicrobial-resistant H. pylori has hampered the successful eradication of frequent chronic infections. Additionally, due to the absence of effective vaccines against H. pylori, a safe vaccine is highly demanded. Disclosed herein are innovative Protective Immunity Enhanced Salmonella Vaccine (PIESV) vector strains to deliver and express multiple H. pylori antigen genes. Immunization of mice with a vaccine delivering the HpaA, NapA (also termed Hp-NAP), UreA and UreB antigens, provided sterile protection against H. pylori SS1 infection in 7 out of 10 tested mice. Compared to the control groups that had received PBS or a PIESV with an empty vector, immunized mice exhibited specific and significant cellular recall responses and antigen-specific IgG2c, IgG1, total IgG and gastric IgA antibody titers. Importantly, the mice immunized with the vaccine candidate showed a significant reduction in a load of an unidentified Gram-positive rod-shaped bacteria in their stomach compared to the control groups. In conclusion, a Salmonella Typhimurium-based live vaccine delivering four antigens shows promise as a safe and effective vaccine against H. pylori infection.

The present disclosure relates to methods and agents for antigen vaccination and inducing effective antigen-specific immune effector cell responses such as T cell responses. These methods and agents are, in particular, useful for the treatment of diseases characterized by diseased cells expressing an antigen the immune effector cells are directed to. In some embodiments, the present disclosure relates to methods comprising administering to a subject (i) non-immunogenic RNA encoding a peptide or polypeptide comprising an epitope for inducing an immune response against an antigen in the subject, i.e., non-immunogenic RNA encoding vaccine antigen; and (ii) a PD-1 axis binding antagonist such as an anti-PD-1 antibody and/or an anti-PD-L1 antibody.

The present disclosure relates to methods and agents for antigen vaccination and inducing effective antigen-specific immune effector cell responses such as T cell responses. These methods and agents are, in particular, useful for the treatment of diseases characterized by diseased cells expressing an antigen the immune effector cells are directed to. In some embodiments, the present disclosure relates to methods comprising administering to a subject (i) non-immunogenic RNA encoding a peptide or polypeptide comprising an epitope for inducing an immune response against an antigen in the subject, i.e., non-immunogenic RNA encoding vaccine antigen; and (ii) a PD-1 axis binding antagonist such as an anti-PD-1 antibody and/or an anti-PD-L1 antibody.