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To combat the surge of viral outbreaks, new treatments are urgently needed. Here, we design a new vaccine based on virus\u2010like particles (VLPs) and show how intranasal administration of this vaccine triggers protective immunity, which can be exploited for the development of new therapies. H1N1 VLPs were produced in baculovirus vectors and were injected into BALB\/c mice by the intramuscular (IM) or intranasal (IN) route. We found that there were significantly higher inflammatory cell and lymphocyte concentrations in bronchoalveolar lavage samples and the lungs of IN immunized mice; however, the IM group had little signs of inflammatory responses. On the basis of our results, immunization with H1N1 influenza VLP elicited a strong T cell immunity in BALB\/c mice. Despite T cell immunity amplification after both IN\u00a0and IM\u00a0vaccination methods in mice, IN\u2010induced T cell responses were significantly more intense than IM\u2010induced responses, and this was likely related to an increased number of both CD11b<jats:sup>high<\/jats:sup> and CD103<jats:sup>+<\/jats:sup> dendritic cells in mice lungs after IN administration of VLP. Furthermore, evaluation of interleukin\u20104 and interferon gamma cytokines along with several chemokine receptors showed that VLP vaccination via IN and IM routes leads to a greater CD4<jats:sup>+<\/jats:sup> Th1 and Th2 response, respectively. Our findings indicated that VLPs represent a potential strategy for the development of an effective influenza vaccine; however, employing relevant routes for vaccination can be another important part of the universal influenza vaccine puzzle.<\/jats:p>","DOI":"10.1002\/jcp.28339","type":"journal-article","created":{"date-parts":[[2019,2,20]],"date-time":"2019-02-20T04:07:56Z","timestamp":1550635676000},"page":"16643-16652","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Induction of protective immune response to intranasal administration of influenza virus\u2010like particles in a mouse model"],"prefix":"10.1002","volume":"234","author":[{"given":"Mohsen","family":"Keshavarz","sequence":"first","affiliation":[{"name":"Department of Virology, School of Medicine Iran University of Medical Sciences Tehran Iran"},{"name":"The Persian Gulf Tropical Medicine Research Center, The Persian Gulf Biomedical Sciences Research Institute Bushehr University of Medical Sciences Bushehr Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haideh","family":"Namdari","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Medicine Tehran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaser","family":"Arjeini","sequence":"additional","affiliation":[{"name":"Virology Department, School of Public Health Tehran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamed","family":"Mirzaei","sequence":"additional","affiliation":[{"name":"Research Center for Biochemistry and Nutrition in Metabolic Diseases Kashan University of Medical Sciences Kashan Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vahid","family":"Salimi","sequence":"additional","affiliation":[{"name":"Virology Department, School of Public Health Tehran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmadreza","family":"Sadeghi","sequence":"additional","affiliation":[{"name":"Iranian Tissue Bank and Research Center Tehran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Talat","family":"Mokhtari\u2010Azad","sequence":"additional","affiliation":[{"name":"Virology Department, School of Public Health Tehran University of Medical Sciences Tehran Iran"},{"name":"National Influenza Center, School of Public Health Tehran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5957-6691","authenticated-orcid":false,"given":"Farhad","family":"Rezaei","sequence":"additional","affiliation":[{"name":"Virology Department, School of Public Health Tehran University of Medical Sciences Tehran Iran"},{"name":"National Influenza Center, School of Public Health Tehran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,2,19]]},"reference":[{"key":"e_1_2_9_1_2_1","doi-asserted-by":"publisher","DOI":"10.21769\/BioProtoc.1972"},{"key":"e_1_2_9_1_3_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0001501"},{"key":"e_1_2_9_1_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2007.01.106"},{"key":"e_1_2_9_1_5_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.169.11.6120"},{"key":"e_1_2_9_1_6_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0311134"},{"issue":"49","key":"e_1_2_9_1_7_1","first-page":"997","article-title":"Estimated influenza illnesses and hospitalizations averted by influenza vaccination\u2010United States, 2012\u201013 influenza season","volume":"62","author":"Control, C. 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