Sublingual administration of liposomes enclosing alpha-galactosylceramide as an effective adjuvant of allergen immunotherapy in a murine model of allergic rhinitis

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Author(s)

    • Suzuki Satoshi
    • Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, Chiba University
    • Ishii Yasuyuki
    • REGiMMUNE Corporation|Cluster for Industry Partnerships (CIP), RIKEN
    • Okamoto Yoshitaka
    • Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, Chiba University
    • Sakurai Daiju
    • Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, Chiba University
    • Sakurai Toshioki
    • Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, Chiba University
    • Yonekura Syuji
    • Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, Chiba University
    • Iinuma Tomohisa
    • Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, Chiba University
    • Okuma Yusuke
    • Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, Chiba University
    • Ihara Fumie
    • Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, Chiba University
    • Arai Tomoyuki
    • Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, Chiba University
    • Hanazawa Toyoyuki
    • Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, Chiba University

Abstract

<p><i>Background:</i> Sublingual immunotherapy (SLIT) is an established efficacious approach for the treatment of allergic rhinitis (AR). However, SLIT requires a long administration period to establish stable and adequate responses. This study investigated the efficacy of the sublingual administration of an allergen with liposomes enclosing α-GalCer (α-GC-liposome) as a potential adjuvant in mice with AR.</p><p><i>Methods:</i> Mice with AR induced by OVA received the sublingual administration of OVA, α-GC-liposomes, or OVA plus α-GC-liposomes for 7 days. After nasal re-challenge with OVA, nasal symptoms were evaluated. The serum levels of OVA-specific Ig, the cytokine production of CD4<sup>+</sup> T cells in the cultures of cervical lymph node (CLN) cells, and the gene expression of CLNs were analyzed.</p><p><i>Results:</i> Although IL-4, IL-5 and IL-13 production from CD4<sup>+</sup> T cells in CLN cells was significantly inhibited by the sublingual administration of OVA alone in mice with AR induced by OVA, their nasal symptoms were not significantly diminished. However, the combined sublingual administration of α-GC-liposomes and OVA completely suppressed nasal symptoms, downregulated Th2 and Th17 type cytokine production in CD4<sup>+</sup> T cells as well as Th2 and Th17 gene expressions, and upregulated Th1 type cytokine production as well as Th1 gene expressions in CLN cells. Additionally, the serum levels of specific IgG2a were promoted, and specific IgE and IgG1 were inhibited.</p><p><i>Conclusions:</i> Our findings suggest that the sublingual administration of an allergen with α-GC-liposomes as an adjuvant might increase the therapeutic efficacy and effectiveness of this treatment method.</p>

Journal

  • Allergology International

    Allergology International 68(3), 352-362, 2019

    Japanese Society of Allergology

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