Epitopic suppression in synthetic vaccine models: analysis of the effector mechanisms |
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| Authors: | M P Schutze C Leclerc F R Vogel L Chedid |
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| Institution: | 1. Division of Pulmonology, Department of Internal Medicine, Charlotte Maxeke Johannesburg Academic Hospital, Johannesburg, South Africa;2. Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa;3. Department of Immunology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa;1. Subdirección General de Epidemiología, Dirección General de Salud Pública, Consejería de Sanidad de la Comunidad de Madrid, Madrid, España;2. Laboratorio Regional de Salud Pública, Dirección General de Salud Pública, Consejería de Sanidad de la Comunidad de Madrid, Madrid, España;3. Subdirección General de Promoción, Prevención y Educación para la Salud, Dirección General de Salud Pública, Consejería de Sanidad de la Comunidad de Madrid, Madrid, España;4. Departamento de Medicina Preventiva y Salud Pública, Universidad Rey Juan Carlos, Madrid, España;5. Servicio de Medicina Preventiva, Hospital Ramón y Cajal, Madrid, España;1. Kumasi Centre for Collaborative Research in Tropical Medicine (KCCR), College of Health Sciences, KNUST, Kumasi, Ghana;2. Department of Biochemistry and Biotechnology, Kwame Nkrumah University Science & Technology, PMB, KNUST, Kumasi, Ghana;3. Department of Theoretical and Applied Biology, Kwame Nkrumah University Science & Technology, PMB, KNUST, Kumasi, Ghana;4. Public Health Reference Laboratory, Ghana Health Service, Accra, Ghana;5. Department of Medicine, Section Tropical Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany;6. Bernhard Nocht Institute for Tropical Medicine (BNITM), Hamburg, Germany;7. Department of Global Health, School of Public Health, College of Health Sciences, Kwame Nkrumah University of Science and Technology, KNUST, Kumasi, Ghana;1. Reference Centre for Pneumococci, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium;2. Department of Microbiology, Immunology and Transplantation, KU Leuven, Herestraat 49, 3000 Leuven, Belgium;3. Centre for the Evaluation of Vaccination, Vaccine and Infectious Disease Institute, University of Antwerp, Campus Drie Eiken, Universiteitsplein 1, 2610 Wilrijk, Belgium;4. Laboratory of Medical Microbiology, Vaccine and Infectious Disease Institute, University of Antwerp, Campus Drie Eiken, Universiteitsplein 1, 2610 Wilrijk, Belgium;5. Centre for Health Economics Research and Modelling Infectious Diseases, University of Antwerp, Campus Drie Eiken, Universiteitsplein 1, 2610 Wilrijk, Belgium;1. Canadian Center for Vaccinology (CCfV), IWK Health Centre, Nova Scotia Health Authority (NSHA), and Dalhousie University, Halifax, Nova Scotia, Canada;2. Division of Microbiology, Department of Pathology and Laboratory Medicine, Nova Scotia Health Authority (NSHA), Halifax, Nova Scotia, Canada;3. National Microbiology Laboratory (NML), Public Health Agency of Canada (PHAC), Winnipeg, Manitoba, Canada;4. Centre Hospitalier Universitaire de Québec, Québec, Québec, Canada;5. Vancouver General Hospital, and University of British Columbia, Vancouver, British Columbia, Canada;6. Mount Sinai Hospital, Toronto, Ontario, Canada;7. Public Health Ontario and University of Toronto, Toronto, Ontario, Canada;8. McMaster University, Hamilton, Ontario, Canada;9. Ottawa Hospital General Campus and University of Ottawa, Ottawa, Ontario, Canada;10. McGill University Health Centre, Montreal, Québec, Canada;11. Centre Intégré Universitaire de Santé et de Services Sociaux de l’Estrie – Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Québec, Canada;12. Saint John Regional Hospital, Saint John, New Brunswick, Canada |
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| Abstract: | The induction of an immune response against synthetic peptides usually requires the use of an immunogenic carrier. The use of tetanus toxoid (TT) has been proposed for this purpose as it is highly immunogenic and has been used extensively in humans. Previous studies have demonstrated that an epitope-specific suppression of IgG antibody responses occurs when mice previously primed with TT are subsequently immunized with SODP, a haptenic epitope linked to TT. In the present investigation, we characterized the effector populations which regulate anti-SODP antibody responses in TT/TT-SODP immunized mice. In vitro studies showed that epitopic suppression did not arise due to nonspecific suppressor phenomena. Coculture experiments demonstrated that epitopic suppression was partially mediated by suppressor T cells which specifically inhibited the anti-hapten but not the anti-carrier antibody response. The majority of these T cells were shown to possess the Lyt-2+ phenotype. Apart from the T suppressor population we demonstrated a deficiency at the B-cell level which contributed to the total suppressive effect. Epitopic suppression, therefore, resulted from the effects of dual specific suppressor mechanisms. |
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