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AssigneeUniversity of Florida Research Foundation, Inc.
InventorsRoy Curtiss, Amir Ghasemi
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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.
An attenuated derivative of an invasive pathogenic microorganism that undergoes regulated delayed lysis in vivo that comprises an expression construct engineered to synthesize at least one Helicobacter protein, the expression construct comprising a polynucleotide sequences encoding the at least one Helicobacter protein, wherein upon administration to an animal host, the microorganism expresses and delivers the at least one Helicobacter protein to the animal host, wherein the attenuated derivative of an invasive pathogenic microorganism comprises a PIESV.
An attenuated derivative of an invasive pathogenic microorganism that undergoes regulated delayed lysis in vivo that comprises an expression construct engineered to synthesize at least three Helicobacter proteins, the expression construct comprising a polynucleotide sequences encoding the at least three Helicobacter proteins, wherein upon administration to an animal host, the microorganism expresses and delivers the at least three Helicobacter proteins to the animal host, wherein the attenuated derivative of an invasive pathogenic microorganism comprises a PIESV.
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