Attenuated Bordetella pertussis Vaccine Protects against Respiratory Syncytial Virus Disease via an IL-17–Dependent Mechanism
| Autor: | Devika Sawant, Peter J. M. Openshaw, Corinna Schnoeller, Wieslawa Olszewska, Dominique Raze, Camille Locht, Xavier Le Roux |
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| Rok vydání: | 2014 |
| Předmět: |
Pulmonary and Respiratory Medicine
Bordetella pertussis Respiratory Syncytial Virus Infections Vaccines Attenuated Critical Care and Intensive Care Medicine Virus Mice 03 medical and health sciences 0302 clinical medicine Immune system medicine Animals Bronchiolitis Viral Administration Intranasal Whooping cough 030304 developmental biology Pertussis Vaccine Mice Inbred BALB C 0303 health sciences Innate immune system biology business.industry Interleukin-17 respiratory system biology.organism_classification medicine.disease Virology Immunity Innate 3. Good health Nasal Mucosa Bronchiolitis Immunology Female Nasal administration business Viral load 030215 immunology |
| Zdroj: | American Journal of Respiratory and Critical Care Medicine. 189:194-202 |
| ISSN: | 1535-4970 1073-449X |
| Popis: | We attenuated virulent Bordetella pertussis by genetically eliminating or detoxifying three major toxins. This strain, named BPZE1, is being developed as a possible live nasal vaccine for the prevention of whooping cough. It is immunogenic and safe when given intranasally in adult volunteers.Before testing in human infants, we wished to examine the potential effect of BPZE1 on a common pediatric infection (respiratory syncytial virus [RSV]) in a preclinical model.BPZE1 was administered before or after RSV administration in adult or neonatal mice. Pathogen replication, inflammation, immune cell recruitment, and cytokine responses were measured.BPZE1 alone did not cause overt disease, but induced efflux of neutrophils into the airway lumen and production of IL-10 and IL-17 by mucosal CD4(+) T cells. Given intranasally before RSV infection, BPZE1 markedly attenuated RSV, preventing weight loss, reducing viral load, and attenuating lung cell recruitment. Given neonatally, BPZE1 also protected against RSV-induced weight loss even through to adulthood. Furthermore, it markedly increased IL-17 production by CD4(+) T cells and natural killer cells and recruited regulatory cells and neutrophils after virus challenge. Administration of anti-IL-17 antibodies ablated the protective effect of BPZE1 on RSV disease.Rather than enhancing RSV disease, BPZE1 protected against viral infection, modified viral responses, and enhanced natural mucosal resistance. Prevention of RSV infection by BPZE1 seems in part to be caused by induction of IL-17. Clinical trial registered with www.clinicaltrials.gov (NCT 01188512). |
| Databáze: | OpenAIRE |
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