Sublingual Immunization With an RSV G Glycoprotein Fragment Primes IL-17-Mediated Immunopathology Upon Respiratory Syncytial Virus Infection
| Autor: | In Su Cheon, Joo Young Kim, Youngjoo Choi, Byoung-Shik Shim, Jung-ah Choi, Dae-Im Jung, Jae-Ouk Kim, Thomas J. Braciale, Hyewon Youn, Man Ki Song, Jun Chang |
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| Rok vydání: | 2019 |
| Předmět: |
CD4-Positive T-Lymphocytes
glycoprotein lcsh:Immunologic diseases. Allergy 0301 basic medicine Neutrophils viruses Immunology Administration Sublingual Respiratory Syncytial Virus Infections Disease sublingual Virus 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Immunopathology Respiratory Syncytial Virus Vaccines Animals immunopathology Immunology and Allergy Medicine Respiratory system Lung Original Research Mice Inbred BALB C business.industry RSV virus diseases respiratory system Eosinophils Vaccination IL-17 030104 developmental biology chemistry Cytokines Female Nasal administration Interleukin 17 Vaccinia lcsh:RC581-607 business Bronchoalveolar Lavage Fluid Viral Fusion Proteins 030215 immunology |
| Zdroj: | Frontiers in Immunology, Vol 10 (2019) Frontiers in Immunology |
| ISSN: | 1664-3224 |
| DOI: | 10.3389/fimmu.2019.00567 |
| Popis: | Respiratory syncytial virus (RSV) is the leading cause of serious respiratory tract disease but there is no licensed RSV vaccine. Immunopathological mechanisms have long been suspected as operating in the development of severe RSV disease and have hampered the development of safe and effective vaccines. Here, we show that unlike intranasal immunization, sublingual immunization with RSV glycoprotein fragment containing the central conserved region (Gcf) primes the host for severe disease upon RSV challenge. This increased pathology does not require replication by the challenge virus and is associated with massive infiltration of inflammatory cells, extensive cell death, and excessive mucus production in the airway and lungs. This exacerbated RSV disease primed by sublingual Gcf immunization is distinct from the immunopathology by G-expressing vaccinia virus or formalin-inactivated RSV, and preceded by prominent IL-17 production. IL-17 deficiency abolished the enhanced disease. Our results suggest a novel mechanism of RSV vaccine-induced immunopathology by IL-17, and highlights the importance of vaccination site. |
| Databáze: | OpenAIRE |
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