title: Virus-like particles presenting interleukin-33 molecules: immunization characteristics and potentials of blockingIL-33/ST2 pathway in allergic airway inflammation.
abstract: We sought to develop an IL-33 vaccine and evaluate its efficacy in a mouse model of asthma. The full-length molecules of putative mature IL-33 were inserted into the immunodominant epitope region of hepatitis B core antigen using gene recombination techniques. The expressed chimeric protein presented as virus-like particles (VLPs) under observation using an electron microscopy. To investigate immunization characteristics of the VLPs, mice were immunized by using different doses, adjuvants, and routes. The VLPs induced sustained and high titers of IL-33-specific IgG and IgA even without the use of a conventional adjuvant, and the lowered ratio of IgG1/IgG2a in vaccinated mice indicated a shift from Th2 to Th1-like responses. To assess the vaccine effects on blocking the signaling of IL-33/ST2 pathway, mice receiving 3 vaccinations subjected to intraperitoneal sensitization and intranasal challenge with ovalbumin (OVA). Control animals received carrier or PBS in place of the vaccine. Immunization with the VLPs significantly suppressed inflammatory cell number and IL-33 level in BALF. OVA -induced goblet cell hyperplasia and lung tissue inflammatory cell infiltration were significantly suppressed in vaccinated mice. Our data indicate that IL-33 molecule-based vaccine, which may block IL-33/ST2 signaling pathway on a persistent basis, holds potential for treatment of asthma and, by extension, other diseases where overexpressed IL-33 plays a pivotal role in pathogenesis.
authors.affiliation: a Lab of Molecular Immunology; Institute of Medical Biology; Chinese Academy of Medical Sciences & Peking Union Medical College; Kunming, PR China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Long
authors.forename: Weiwei
authors.initials: W
authors.lastname: Huang
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Yao
authors.forename: Xu
authors.initials: X
authors.lastname: Yang
authors.forename: Wenjia
authors.initials: W
authors.lastname: Sun
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Jin
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Chu
authors.forename: Cunbao
authors.initials: C
authors.lastname: Liu
authors.forename: Zhikang
authors.initials: Z
authors.lastname: Peng
authors.forename: Yanbing
authors.initials: Y
authors.lastname: Ma
mesh_terms: D000818:Animals; D001249:Asthma / Q000628:therapy*; D004195:Disease Models, Animal; D005260:Female; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007167:Immunotherapy / Q000379:methods*; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D007378:Interleukins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology*; D008807:Mice, Inbred BALB C; D046529:Microscopy, Electron, Transmission; D018123:Receptors, Interleukin / Q000037:antagonists & inhibitors*; D015398:Signal Transduction; D058425:Vaccines, Virus-Like Particle / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D022701:Virosomes / Q000648:ultrastructure
chemical_list: C486189:Il1rl1 protein, mouse; C506535:Il33 protein, mouse; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D007378:Interleukins; D018123:Receptors, Interleukin; D058425:Vaccines, Virus-Like Particle; D022701:Virosomes
keywords: animal model; asthma; cytokine; inflammation; interleukin (IL)-33; vaccine; virus-like particles (VLPs)