Lectures and seminars MTC Infection and Immunology Seminar: "Therapeutic vaccination with Helicobacter pylori attachment protein protects against gastric cancer"
Welcome to a seminar with Professor Thomas Boren, Department of Medical Biochemistry and Biophysics, Umeå University, Sweden.
Host
Please contact Ute Römling or Daniel Sorobetea if you want to meet Professor Boren.
Abstract
Helicobacter pylori infection causes chronic active gastritis and peptic ulcer disease. In the western world, 10 percent (22 million individuals) develop peptic ulcers. Furthermore, H. pylori infection is tightly correlated with development of gastric cancer with >500.000 mortalities/year and H. pylori has been defined a carcinogen by the WHO.
Thomas Boren has been among the poineers studying protein-carbohydrate interactions that mediate adherence of H. pylori to stomach tissue. He is focusing on the Blood Group Antigen Binding Adhesin, BabA, which is the key player attachment protein that targets H. pylori binding to the stomach lining. Bacterial adherence is mediated by high-affinity (strong) binding to carbohydrates such as ABO antigens (displayed by the common ABO-blood group system).
Recently, Prof. Boren has developed H. pylori adhesin proteins into novel vaccine candidates using the transgenic "Lewis b mouse" with results experimentally verified in human volunteers.
Early work
Aspholm-Hurtig M, Dailide G, Lahmann M, Kalia A, Ilver D, Roche N, VikströmS, Sjöström R, Lindén S, Bäckström A, Lundberg C, Arnqvist A, Mahdavi J, NilssonUJ, Velapatiño B, Gilman RH, Gerhard M, Alarcon T, López-Brea M, Nakazawa T, FoxJG, Correa P, Dominguez-Bello MG, Perez-Perez GI, Blaser MJ, Normark Carlstedt I, Oscarson S, Teneberg S, Berg DE, Borén T. Functional adaptation ofBabA, the H. pylori ABO blood group antigen binding adhesin. Science. 2004 Jul23;305(5683):519-22. doi: 10.1126/science.1098801. PMID: 15273394.
Mahdavi J, Sondén B, Hurtig M, Olfat FO, Forsberg L, Roche N, Angstrom J,Larsson T, Teneberg S, Karlsson KA, Altraja S, Wadström T, Kersulyte D, Berg DE,Dubois A, Petersson C, Magnusson KE, Norberg T, Lindh F, Lundskog BB, ArnqvistA, Hammarström L, Borén T. Helicobacter pylori SabA adhesin in persistentinfection and chronic inflammation. Science. 2002 Jul 26;297(5581):573-8. doi:10.1126/science.1069076. PMID: 12142529; PMCID: PMC2570540.
Ilver D, Arnqvist A, Ogren J, Frick IM, Kersulyte D, Incecik ET, Berg DE, Covacci A, Engstrand L, Borén T. Helicobacter pylori adhesin binding fucosylated histo-blood group antigens revealed by retagging. Science. 1998 Jan 16;279(5349):373-7. doi: 10.1126/science.279.5349.373. PMID: 9430586.
Borén T, Falk P, Roth KA, Larson G, Normark S. Attachment of Helicobacter pylori to human gastric epithelium mediated by blood group antigens. Science 1993 Dec 17;262(5141):1892-5. doi: 10.1126/science.8018146. PMID: 8018146.
Recent references
Bugaytsova JA, Piddubnyi A, Tkachenko I, Rakhimova L, Edlund JO, Thorell K, Marcotte H, Lundquist A, Schön K, Lycke N, Suerbaum S, Schulz C, Malfertheiner P, Hansen LM, Solnick JV, Moskalenko R, Hammarström L, Borén T. Vaccination with Helicobacter pylori attachment proteins protects against gastric cancer bioRxiv [Preprint]. 2023 Jul 4:2023.05.25.542131. doi: 10.1101/2023.05.25.542131. PMID: 37461695; PMCID: PMC10349987.
Bugaytsova JA, Moonens K, Piddubnyi A, Schmidt A, Edlund JO, Lisiutin G, Brännström K, Chernov YA, Thorel K, Tkachenko I, Sharova O, Vikhrova I, Butsy A, Shubin P, Chyzhma R, Johansson DX, Marcotte H, Sjöström R, Shevtsova A, Bylund G, Rakhimova L, Lundquist A, Berhilevych O, Kasianchuk V, Loboda A, Ivanytsia V, Hultenby K, Persson MAA, Gomes J, Matos R, Gartner F, Reis CA, Whitmire JM, Merrell DS, Pan-Hammarström Q, Landström M, Oscarson S, D'Elios MM, Agreus L, Ronkainen J, Aro P, Engstrand L, Graham DY, Kachkovska V, Mukhopadhyay A, Chaudhuri S, Karmakar BC, Paul S, Kravets O, Camorlinga M, Torres J, Berg DE, Moskalenko R, Haas R, Remaut H, Hammarström L, Borén T. Helicobacter pylori attachment-blocking antibodies protect against duodenal ulcer disease. bioRxiv [Preprint]. 2023 May 24:2023.05.24.542096. doi: 10.1101/2023.-05.24.542096. PMID: 37292721; PMCID: PMC10245814.
Reihill M, Fournière V, Cheallaigh AN, Edlund JO, Miller GJ, Borén T, Lahmann M, Oscarson S. Synthesis of a B-Antigen Hexasaccharide, a B-Lewis b Heptasaccharide and Glycoconjugates Thereof to Investigate Binding Properties of Helicobacter pylori. Chemistry. 2023 Mar 16;29(16):e202203672. doi: 10.1002/chem.202203672. Epub 2023 Feb 15. PMID: 36562295.
Mthembu YH, Jin C, Padra M, Liu J, Edlund JO, Ma H, Padra J, Oscarson S, Borén T, Karlsson NG, Lindén SK, Holgersson J. Recombinant mucin-type proteins carrying LacdiNAc on different O-glycan core chains fail to support H. pylori binding. Mol Omics. 2020 Jun 1;16(3):243-257. doi: 10.1039/c9mo00175a. Epub 2020 Apr 8. PMID: 32267274.
Jin C, Barone A, Borén T, Teneberg S. Helicobacter pylori-binding nonacid glycosphingolipids in the human stomach. J Biol Chem. 2018 Nov 2;293(44):17248-17266. doi: 10.1074/jbc.RA118.004854. Epub 2018 Sep 19. PMID: 30232154; PMCID: PMC6222098.
Esberg A, Sheng N, Mårell L, Claesson R, Persson K, Borén T, Strömberg N. Streptococcus Mutans Adhesin Biotypes that Match and Predict Individual Caries Development. EBioMedicine. 2017 Oct;24:205-215. doi: 10.1016/j.ebiom.2017.09.027. Epub 2017 Sep 21. PMID: 28958656; PMCID: PMC5652290.