Sustained protective immunity against Bordetella pertussis nasal colonization by intranasal immunization with a vaccine-adjuvant combination that induces IL-17-secreting T
| Autor: | Mieszko M. Wilk, Aideen C. Allen, Alicja Misiak, Lisa Borkner, Dearbhla M. Murphy, Kingston H. G. Mills |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Bordetella pertussis Whooping Cough medicine.medical_treatment Immunology Nose 03 medical and health sciences Mice Adjuvants Immunologic Immunity medicine Immunology and Allergy Animals Humans Administration Intranasal Cells Cultured Pertussis Vaccine Immunity Cellular biology business.industry Interleukin-17 Vaccination Th1 Cells biology.organism_classification Mice Inbred C57BL 030104 developmental biology Immunization biology.protein Pertussis vaccine Th17 Cells Nasal administration Antibody business Adjuvant Immunologic Memory medicine.drug |
| Zdroj: | Mucosal immunology. 11(6) |
| ISSN: | 1935-3456 |
| Popis: | Current acellular pertussis (aP) vaccines induce strong antibody and Th2 responses but fail to protect against nasal colonization and transmission of Bordetella pertussis. Furthermore, immunity wanes rapidly after immunization. We have developed a novel adjuvant combination (called LP-GMP), comprising c-di-GMP, an intracellular receptor stimulator of interferon genes (STING) agonist, and LP1569, a TLR2 agonist from B. pertussis, which synergistically induces production of IFN-β, IL-12 and IL-23, and maturation of dendritic cells. Parenteral immunization of mice with an experimental aP vaccine formulated with LP-GMP promoted Th1 and Th17 responses and conferred protection against lung infection with B. pertussis. Intranasal immunization with the same aP vaccine-induced potent B. pertussis-specific Th17 responses and IL-17-secreting respiratory tissue-resident memory (TRM) CD4 T cells, and conferred a high level of protection against nasal colonization as well as lung infection, which was sustained for at least 10 months. Furthermore, long-term protection against nasal colonization with B. pertussis correlated with the number of IL-17-secreting TRM cells in nasal tissue. Our study has identified an approach for inducing IL-17-secreting TRM cells that sustain sterilizing immunity against nasal colonization of mice with B. pertussis, and could form the basis of a third generation pertussis vaccine for humans. |
| Databáze: | OpenAIRE |
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