Sublingual Immunization With an RSV G Glycoprotein Fragment Primes IL-17-Mediated Immunopathology Upon Respiratory Syncytial Virus Infection
- 주제(키워드) RSV , glycoprotein , sublingual , IL-17 , immunopathology
- 주제(기타) Immunology
- 설명문(일반) [Cheon, In Su; Choi, Youngjoo; Shim, Byoung-Shik; Choi, Jung-ah; Jung, Dae-Im; Kim, Jae-Ouk; Song, Man Ki] Int Vaccine Inst, Lab Sci Div, Seoul, South Korea; [Kim, Joo Young; Chang, Jun] Ewha Womans Univ, Grad Sch Pharmaceut Sci, Seoul, South Korea; [Braciale, Thomas J.] Univ Virginia, Beirne B Carter Ctr Immunol Res, Charlottesville, VA USA; [Braciale, Thomas J.] Univ Virginia, Dept Pathol, Charlottesville, VA 22903 USA; [Youn, Hyewon] Seoul Natl Univ, Coll Med, Canc Res Inst, Dept Nucl Med, Seoul, South Korea; [Youn, Hyewon] Seoul Natl Univ Hosp, Canc Imaging Ctr, Seoul, South Korea
- 등재 SCIE, SCOPUS
- OA유형 gold, Green Published
- 발행기관 FRONTIERS MEDIA SA
- 발행년도 2019
- URI http://www.dcollection.net/handler/ewha/000000160046
- 본문언어 영어
- Published As http://dx.doi.org/10.3389/fimmu.2019.00567
- PubMed https://pubmed.ncbi.nlm.nih.gov/30984173
초록/요약
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.
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