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

Miura Naoya; Shaheen Sharif M.; Akita Hidetaka; Nakamura Takashi; Harashima Hideyoshi

Title	en 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	en Miura, Naoya en Shaheen, Sharif M. en Akita, Hidetaka NRID 1000080344472 en Nakamura, Takashi NRID 1000020604458 en Harashima, Hideyoshi NRID 1000000183567
Accessrights	open access
Rights	http://creativecommons.org/licenses/by/4.0/ en Creative Commons Attribution 4.0 International
Subject	NDC 499
Description	Abstract en 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.
Publisher	en Oxford University Press
Date	Issued2015-02-19
Language	eng
Resource Type	journal article
Version Type	VoR
Identifier	HDL http://hdl.handle.net/2115/59281
Relation	isIdenticalTo DOI https://doi.org/10.1093/nar/gkv008
Journal	PISSN 0305-1048 en Nucleic acids research Volume Number43 Issue Number3 Page Start1317 Page End1331
File	fulltext NAR43-3 1317-1331.pdf 1.91 MB (application/pdf) Issued2015-02-19
Oaidate	2023-07-26