Sublingual immunization with an RSV G glycoprotein fragment primes IL-17-mediated immunopathology upon respiratory syncytial virus infection

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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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.

Original languageEnglish
Article number567
JournalFrontiers in Immunology
Issue numberMAR
StatePublished - 2019

Bibliographical note

Publisher Copyright:
Copyright © 2019 Cheon, Kim, Choi, Shim, Choi, Jung, Kim, Braciale, Youn, Song and Chang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.


  • Glycoprotein
  • IL-17
  • Immunopathology
  • RSV
  • Sublingual


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