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 Song; Dae Gwin Jeong; Gyochang Keum; Jae Hwan Nam

doi:10.1002/anie.202002979

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

Department of Pharmaceutical Sciences

Research output: Contribution to journal › Article › peer-review

11 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 language	English
Pages (from-to)	11540-11549
Number of pages	10
Journal	Angewandte Chemie - International Edition
Volume	59
Issue number	28
DOIs	https://doi.org/10.1002/anie.202002979
State	Published - 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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1002/anie.202002979

Cite this

Park, H. J., Bang, E. K., Hong, J. J., Lee, S. M., Ko, H. L., Kwak, H. W., Park, H., Kang, K. W., Kim, R. H., Ryu, S. R., Kim, G., Oh, H., Kim, H. J., Lee, K., Kim, M., Kim, S. Y., Kim, J. O., El-Baz, K., Lee, H., ... Nam, J. H. (2020). Nanoformulated Single-Stranded RNA-Based Adjuvant with a Coordinative Amphiphile as an Effective Stabilizer: Inducing Humoral Immune Response by Activation of Antigen-Presenting Cells. Angewandte Chemie - International Edition, 59(28), 11540-11549. https://doi.org/10.1002/anie.202002979

@article{9ab02876f19c485e8936f488389c9e39,

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

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.",

keywords = "amphiphiles, antigens, nanoparticles, RNA structures, viruses",

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

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: {\textcopyright} 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim",

year = "2020",

month = jul,

day = "6",

doi = "10.1002/anie.202002979",

language = "English",

volume = "59",

pages = "11540--11549",

journal = "Angewandte Chemie - International Edition",

issn = "1433-7851",

publisher = "John Wiley and Sons Ltd",

number = "28",

}

Park, HJ, Bang, EK, Hong, JJ, Lee, SM, Ko, HL, Kwak, HW, Park, H, Kang, KW, Kim, RH, Ryu, SR, Kim, G, Oh, H, Kim, HJ, Lee, K, Kim, M, Kim, SY, Kim, JO, El-Baz, K, Lee, H, Song, M, Jeong, DG, Keum, G & Nam, JH 2020, 'Nanoformulated Single-Stranded RNA-Based Adjuvant with a Coordinative Amphiphile as an Effective Stabilizer: Inducing Humoral Immune Response by Activation of Antigen-Presenting Cells', Angewandte Chemie - International Edition, vol. 59, no. 28, pp. 11540-11549. https://doi.org/10.1002/anie.202002979

Nanoformulated Single-Stranded RNA-Based Adjuvant with a Coordinative Amphiphile as an Effective Stabilizer: Inducing Humoral Immune Response by Activation of Antigen-Presenting Cells. / Park, Hyo Jung; Bang, Eun Kyoung; Hong, Jung Joo et al.
In: Angewandte Chemie - International Edition, Vol. 59, No. 28, 06.07.2020, p. 11540-11549.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Nanoformulated Single-Stranded RNA-Based Adjuvant with a Coordinative Amphiphile as an Effective Stabilizer

T2 - Inducing Humoral Immune Response by Activation of Antigen-Presenting Cells

AU - Park, Hyo Jung

AU - Bang, Eun Kyoung

AU - Hong, Jung Joo

AU - Lee, Sang Myeong

AU - Ko, Hae Li

AU - Kwak, Hye Won

AU - Park, Hyelim

AU - Kang, Kyung Won

AU - Kim, Rhoon Ho

AU - Ryu, Seung Rok

AU - Kim, Green

AU - Oh, Hanseul

AU - Kim, Hye Jung

AU - Lee, Kyuri

AU - Kim, Minjeong

AU - Kim, Soo Young

AU - Kim, Jae Ouk

AU - El-Baz, Karim

AU - Lee, Hyukjin

AU - Song, Manki

AU - Jeong, Dae Gwin

AU - Keum, Gyochang

AU - Nam, Jae Hwan

N1 - 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

PY - 2020/7/6

Y1 - 2020/7/6

N2 - 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.

AB - 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.

KW - amphiphiles

KW - antigens

KW - nanoparticles

KW - RNA structures

KW - viruses

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U2 - 10.1002/anie.202002979

DO - 10.1002/anie.202002979

M3 - Article

C2 - 32239636

AN - SCOPUS:85085142981

SN - 1433-7851

VL - 59

SP - 11540

EP - 11549

JO - Angewandte Chemie - International Edition

JF - Angewandte Chemie - International Edition

IS - 28

ER -

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

Abstract

Bibliographical note

Keywords

UN SDGs

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