Sublingual Immunization With an RSV G Glycoprotein Fragment Primes IL-17-Mediated Immunopathology Upon Respiratory Syncytial Virus Infection

Frontiers in Immunology

Hyewon Youn¹  Joo Young Kim³  Jun Chang³  In Su Cheon⁴  Youngjoo Choi⁴  Man Ki Song⁴  Byoung-Shik Shim⁴  Jung-ah Choi⁴  Dae-Im Jung⁴  Jae-Ouk Kim⁴  Thomas J. Braciale⁵ 

[1] Cancer Imaging Center, Seoul National University Hospital, Seoul, South Korea;Department of Nuclear Medicine, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea;Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, South Korea;Laboratory Science Division, International Vaccine Institute, Seoul, South Korea;The Beirne B. Carter Center for Immunology Research and Department of Pathology, The University of Virginia, Charlottesville, VA, United States;

关键词: RSV;    glycoprotein;    sublingual;    IL-17;    immunopathology;   

DOI  :  10.3389/fimmu.2019.00567

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown