Monoclonal antibodies against fimbrial subunits of colonization factor antigen I (CFA/I) inhibit binding to human enterocytes and protect against enterotoxigenicEscherichia coliexpressing heterologous colonization factors |
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| Institution: | 1. Department of Medical Microbiology and Immunology, Göteborg University, Guldhedsgatan 10 A, 413 46 Göteborg, Sweden;2. Department of Surgery, Göteborg University, Guldhedsgatan 10 A, 413 46 Göteborg, Sweden;1. State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, PR China;2. Department of Bioinformatics and Biological Statistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, PR China;3. State Key Laboratory of Microbial Metabolism, Shanghai-Islamabad-Belgrade Joint Innovation Center on Antibacterial Resistances, Joint Laboratory of International Cooperation in Metabolic and Developmental Sciences, Ministry of Education and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200030, PR China;4. Peng Cheng Laboratory, Vanke Cloud City Phase I Building 8, Xili Street, Nashan District, Shenzhen, Guangdong, 518055, PR China;5. Joint International Research Laboratory of Metabolic & Developmental Sciences, Shanghai Jiao Tong University, Shanghai, PR China;1. School of Life Science and Biotechnology, Dalian University of Technology, Dalian 116024, China;2. School of Software, Dalian University of Technology, Dalian 116620, China;1. Department of Cell Biology, Ludwig Center at Harvard, Harvard Medical School, Boston, MA 02115, USA;2. Stem Cell and Regenerative Biology Department, Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138;3. Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114, USA;4. Cancer Research Institute, Beth Israel Deaconess Cancer Center, Department of Medicine and Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA;5. Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02115, USA;6. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA;7. Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA;1. Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA;2. MRC Tropical Epidemiology Group, London School of Hygiene & Tropical Medicine, London, UK;3. Initiative for Vaccine Research, World Health Organization, CH-1211 Geneva 27, Switzerland;1. Department of Medicine, Division of Rheumatology, Perelman School of Medicine, Institute for Immunology, University of Pennsylvania, Philadelphia, PA 19104, USA;2. Corporal Michael J Crescenz VA Medical Center, Philadelphia, PA 19104, USA;3. Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA;4. Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA;5. Department of Biological Engineering, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA;6. Department of Biology, Emory University, Atlanta, GA, USA;7. Department of Microbiology and Immunology, Emory University, Atlanta, GA, USA;1. Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT 84112, USA |
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| Abstract: | EnterotoxigenicEscherichia coli(ETEC) bind to enterocytes in the small intestine by means of antigenically distinct colonization factors (CFs). By immunizing with isolated subunits of CFA/I fimbriae we have previously produced monoclonal antibodies (MAbs) that cross-react immunologicallyin vitrowith several CFs. Two of these MAbs S(subunit)-CFA/I 17:8 and S-CFA/I 5:6] were found to significantly inhibit the binding of ETEC strains expressing either homologous or heterologous CFs, i.e. CFA/I and CS4, to isolated human jejunal enterocytes. The two MAbs also conferred passive protection against fluid accumulation in rabbit ileal loops caused by CFA/I- as well as CS4-expressing ETEC strains. Immunoelectron microscopy studies showed that both MAbs bound specifically to CFA/I as well as to CS4 fimbriae expressed on bacteria. These results indicate the possibility to induce anti-CF antibodies that can protect against ETEC infection caused by bacteria expressing not only homologous but also heterologous CFs, by immunizing with fimbrial subunits. |
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