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Title
  • A KALA-modified lipid nanoparticle containing CpG-free plasmid DNA as a potential DNA vaccine carrier for antigen presentation and as an immune-stimulative adjuvant
Creator

Miura, Naoya

Shaheen, Sharif M.

Akita, Hidetaka

Nakamura, Takashi

Harashima, Hideyoshi

Rights
    • http://creativecommons.org/licenses/by/4.0/
Subject
  • NDC 499
Description
Other
  • Technologies that delivery antigen-encoded plasmid DNA (pDNA) to antigen presenting cell and their immune-activation are required for the success of DNA vaccines. Here we report on an artificial nanoparticle that can achieve these; a multifunctional envelope-type nanodevice modified with KALA, a peptide that forms alpha-helical structure at physiological pH (KALA-MEND). KALA modification and the removal of the CpG-motifs from the pDNA synergistically boosted transfection efficacy. In parallel, transfection with the KALA-MEND enhances the production of multiple cytokines and chemokines and co-stimulatory molecules via the Toll-like receptor 9-independent manner. Endosome-fusogenic lipid envelops and a long length of pDNA are essential for this immune stimulation. Furthermore, cytoplasmic dsDNA sensors that are related to the STING/TBK1 pathway and inflammasome are involved in IFN-beta and IL-1 beta production, respectively. Consequently, the robust induction of antigen-specific cytotoxic T-lymphoma activity and the resulting prophylactic and therapeutic anti-tumor effect was observed in mice that had been immunized with bone marrow-derived dendritic cells ex vivo transfected with antigen-encoding pDNA. Collectively, the KALA-MEND possesses dual functions; gene transfection system and immune-stimulative adjuvant, those are both necessary for the successful DNA vaccine.
PublisherOxford University Press
Date Issued 2015-02-19
Languageeng
NIItypejournal article
VersiontypeVoR
Identifier URI http://hdl.handle.net/2115/59281
Relation
  • isIdenticalTo DOI https://doi.org/10.1093/nar/gkv008
Journal
    • ISSN 0305-1048
    • Nucleic acids research
    43(3), 1317-1331
File
Oaidate2017-10-15T15:00:00Z