Nanoformulated Single-Stranded RNA-Based Adjuvant with a Coordinative Amphiphile as an Effective Stabilizer: Inducing Humoral Immune Response by Activation of Antigen-Presenting Cells

Hyo Jung Park, Eun Kyoung Bang, Jung Joo Hong, Sang Myeong Lee, Hae Li Ko, Hye Won Kwak, Hyelim Park, Kyung Won Kang, Rhoon Ho Kim, Seung Rok Ryu, Green Kim, Hanseul Oh, Hye Jung Kim, Kyuri Lee, Minjeong Kim, Soo Young Kim, Jae Ouk Kim, Karim El-Baz, Hyukjin Lee, Manki SongDae Gwin Jeong, Gyochang Keum, Jae Hwan Nam

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

As agonists of TLR7/8, single-stranded RNAs (ssRNAs) are safe and promising adjuvants that do not cause off-target effects or innate immune overactivation. However, low stability prevents them from mounting sufficient immune responses. This study evaluates the adjuvant effects of ssRNA derived from the cricket paralysis virus intergenic region internal ribosome entry site, formulated as nanoparticles with a coordinative amphiphile, containing a zinc/dipicolylamine complex moiety as a coordinative phosphate binder, as a stabilizer for RNA-based adjuvants. The nanoformulated ssRNA adjuvant was resistant to enzymatic degradation in vitro and in vivo, and that with a coordinative amphiphile bearing an oleyl group (CA-O) was approximately 100 nm, promoted effective recognition, and improved activation of antigen-presenting cells, leading to better induction of neutralizing antibodies following single immunization. Hence, CA-O may increase the efficacy of ssRNA-based adjuvants, proving useful to meet the urgent need for vaccines during pathogen outbreaks.

Original languageEnglish
Pages (from-to)11540-11549
Number of pages10
JournalAngewandte Chemie - International Edition
Volume59
Issue number28
DOIs
StatePublished - 6 Jul 2020

Bibliographical note

Funding Information:
J.‐H. Nam received grants from the Korean Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI15C2955), the Basic Science Research Program through the National Research Foundation (NRF) funded by the Ministry of Science, ICT & Future Planning (NRF‐2015M3A9B5030157), and the Catholic University of Korea, Research Fund, 2019. G. Keum was supported by the KIST institutional project (2E30180). E.‐K. Bang received a grant from the Basic Science Research Program through the NRF of Korea (2014R1A6A3A04059719). M. Song received a grant from the Ministry of Health & Welfare, Republic of Korea (HI15C2971). J.J. Hong received grants from the Korea Research Institute of Bioscience and Biotechnology Research Initiative Program (KGM 4571922) and KHIDI, funded by the Ministry of Health & Welfare, Republic of Korea (BGC1691811).

Funding Information:
J.-H. Nam received grants from the Korean Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI15C2955), the Basic Science Research Program through the National Research Foundation (NRF) funded by the Ministry of Science, ICT & Future Planning (NRF-2015M3A9B5030157), and the Catholic University of Korea, Research Fund, 2019. G. Keum was supported by the KIST institutional project (2E30180). E.-K. Bang received a grant from the Basic Science Research Program through the NRF of Korea (2014R1A6A3A04059719). M. Song received a grant from the Ministry of Health & Welfare, Republic of Korea (HI15C2971). J.J. Hong received grants from the Korea Research Institute of Bioscience and Biotechnology Research Initiative Program (KGM 4571922) and KHIDI, funded by the Ministry of Health & Welfare, Republic of Korea (BGC1691811).

Publisher Copyright:
© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Keywords

  • amphiphiles
  • antigens
  • nanoparticles
  • RNA structures
  • viruses

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