HelicoVax: Epitope-based therapeutic H. pylori vaccination in a mouse model

Helicobacter pylori is the leading cause of gastritis, peptic ulcer disease and gastric adenocarcinoma and lymphoma in humans. Due to the decreasing efficacy of anti-H. pylori antibiotic therapy in clinical practice, there is renewed interest in the development of anti-H. pylori vaccines. In this study an in silico-based approach was utilized to develop a multi-epitope DNAprime/peptide-boost immunization strategy using informatics tools. The efficacy of this construct was then assessed as a therapeutic vaccine in a mouse model of gastric cancer induced by chronic H. pylori infection. The multi-epitope vaccine administered intranasally induced a broad immune response as determined by interferon-gamma production in ELISpot assays. This was associated with a significant reduction in H. pylori colonization compared with mice immunized with the same vaccine intramuscularly, given an empty plasmid, or given a whole H. pylori lysate intranasally as the immunogen. Total scores of gastric histological changes were not significantly different among the 4 experimental groups. These results suggest that further development of an epitope-based mucosal vaccine may be beneficial in eradicating H. pylori and reducing the burden of the associated gastric diseases in humans. © 2011 Elsevier Ltd. All rights reserved. *Correspondence to: Steven F. Moss, M.D., Gastroenterology Division, Rhode Island Hospital, 593 Eddy Street, APC 414, Providence, RI 02903. Tel: (401) 444-6713; Fax: (401) 444-2939. Steven_Moss@Brown.edu. Current affiliations: Woojin Kim: Gastroenterology Division, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA Dong Soo Lee: Daejeon St. Mary's Hospital, Catholic University of Korea, Daejeon, Republic of Korea Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Two of the contributing authors, Anne S. De Groot and William D. Martin are senior officers and majority shareholders at EpiVax, Inc., a privately-owned vaccine design company located in Providence, RI. Dr. De Groot is also a faculty member at the University of Rhode Island and Brown University. Conflict of interest statement These authors acknowledge that there is a potential conflict of interest related to their relationship with EpiVax and attest that the work contained in this research report is free of any bias that might be associated with the commercial goals of the company. NIH Public Access Author Manuscript Vaccine. Author manuscript; available in PMC 2012 March 3. Published in final edited form as: Vaccine. 2011 March 3; 29(11): 2085–2091. doi:10.1016/j.vaccine. 2010.12. 130. N IH PA Athor M anscript N IH PA Athor M anscript N IH PA Athor M anscript