Sublingual Immunization With an RSV G Glycoprotein Fragment Primes IL-17-Mediated Immunopathology Upon Respiratory Syncytial Virus Infection
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 vacci...
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doaj-d5925b5f7c474c20bbe6387671514c6d2020-11-24T20:53:07ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-03-011010.3389/fimmu.2019.00567425356Sublingual Immunization With an RSV G Glycoprotein Fragment Primes IL-17-Mediated Immunopathology Upon Respiratory Syncytial Virus InfectionIn Su Cheon0Joo Young Kim1Youngjoo Choi2Byoung-Shik Shim3Jung-ah Choi4Dae-Im Jung5Jae-Ouk Kim6Thomas J. Braciale7Hyewon Youn8Hyewon Youn9Man Ki Song10Jun Chang11Laboratory Science Division, International Vaccine Institute, Seoul, South KoreaGraduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, South KoreaLaboratory Science Division, International Vaccine Institute, Seoul, South KoreaLaboratory Science Division, International Vaccine Institute, Seoul, South KoreaLaboratory Science Division, International Vaccine Institute, Seoul, South KoreaLaboratory Science Division, International Vaccine Institute, Seoul, South KoreaLaboratory Science Division, International Vaccine Institute, Seoul, South KoreaThe Beirne B. Carter Center for Immunology Research and Department of Pathology, The University of Virginia, Charlottesville, VA, United StatesDepartment of Nuclear Medicine, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South KoreaCancer Imaging Center, Seoul National University Hospital, Seoul, South KoreaLaboratory Science Division, International Vaccine Institute, Seoul, South KoreaGraduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, South KoreaRespiratory 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.https://www.frontiersin.org/article/10.3389/fimmu.2019.00567/fullRSVglycoproteinsublingualIL-17immunopathology |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
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 Hyewon Youn Man Ki Song Jun Chang |
spellingShingle |
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 Hyewon Youn Man Ki Song Jun Chang Sublingual Immunization With an RSV G Glycoprotein Fragment Primes IL-17-Mediated Immunopathology Upon Respiratory Syncytial Virus Infection Frontiers in Immunology RSV glycoprotein sublingual IL-17 immunopathology |
author_facet |
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 Hyewon Youn Man Ki Song Jun Chang |
author_sort |
In Su Cheon |
title |
Sublingual Immunization With an RSV G Glycoprotein Fragment Primes IL-17-Mediated Immunopathology Upon Respiratory Syncytial Virus Infection |
title_short |
Sublingual Immunization With an RSV G Glycoprotein Fragment Primes IL-17-Mediated Immunopathology Upon Respiratory Syncytial Virus Infection |
title_full |
Sublingual Immunization With an RSV G Glycoprotein Fragment Primes IL-17-Mediated Immunopathology Upon Respiratory Syncytial Virus Infection |
title_fullStr |
Sublingual Immunization With an RSV G Glycoprotein Fragment Primes IL-17-Mediated Immunopathology Upon Respiratory Syncytial Virus Infection |
title_full_unstemmed |
Sublingual Immunization With an RSV G Glycoprotein Fragment Primes IL-17-Mediated Immunopathology Upon Respiratory Syncytial Virus Infection |
title_sort |
sublingual immunization with an rsv g glycoprotein fragment primes il-17-mediated immunopathology upon respiratory syncytial virus infection |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2019-03-01 |
description |
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. |
topic |
RSV glycoprotein sublingual IL-17 immunopathology |
url |
https://www.frontiersin.org/article/10.3389/fimmu.2019.00567/full |
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