Sugar-Nanocapsules Imprinted with Microbial Molecular Patterns for mRNA Vaccination

Sejin Son; Jutaek Nam; Ilia Zenkov; Lukasz J. Ochyl; Yao Xu; Lindsay Scheetz; Jinjun Shi; Omid C. Farokhzad; James J. Moon

doi:10.1021/acs.nanolett.9b03483

Sugar-Nanocapsules Imprinted with Microbial Molecular Patterns for mRNA Vaccination

Sejin Son, Jutaek Nam, Ilia Zenkov, Lukasz J. Ochyl, Yao Xu, Lindsay Scheetz, Jinjun Shi, Omid C. Farokhzad, James J. Moon

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

82 Scopus citations

Abstract

Innate immune cells recognize and respond to pathogen-associated molecular patterns. In particular, polysaccharides found in the microbial cell wall are potent activators of dendritic cells (DCs). Here, we report a new class of nanocapsules, termed sugar-capsules, entirely composed of polysaccharides derived from the microbial cell wall. We show that sugar-capsules with a flexible polysaccharide shell and a hollow core efficiently drain to lymph nodes and activate DCs. In particular, sugar-capsules composed of mannan (Mann-capsule) carrying mRNA (mRNA) promote strong DC activation, mRNA translation, and antigen presentation on DCs. Mann-capsules elicit robust antigen-specific CD4+ and CD8α+ T-cell responses with antitumor efficacy in vivo. The strategy presented in this study is generally applicable for utilizing pathogen-derived molecular patterns for vaccines and immunotherapies.

Original language	English
Pages (from-to)	1499-1509
Number of pages	11
Journal	Nano Letters
Volume	20
Issue number	3
DOIs	https://doi.org/10.1021/acs.nanolett.9b03483
State	Published - 11 Mar 2020
Externally published	Yes

Bibliographical note

Publisher Copyright:
Copyright © 2020 American Chemical Society.

Keywords

dendritic cell
mRNA
nanoparticle
polysaccharide
vaccine

UN SDGs

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

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10.1021/acs.nanolett.9b03483

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title = "Sugar-Nanocapsules Imprinted with Microbial Molecular Patterns for mRNA Vaccination",

abstract = "Innate immune cells recognize and respond to pathogen-associated molecular patterns. In particular, polysaccharides found in the microbial cell wall are potent activators of dendritic cells (DCs). Here, we report a new class of nanocapsules, termed sugar-capsules, entirely composed of polysaccharides derived from the microbial cell wall. We show that sugar-capsules with a flexible polysaccharide shell and a hollow core efficiently drain to lymph nodes and activate DCs. In particular, sugar-capsules composed of mannan (Mann-capsule) carrying mRNA (mRNA) promote strong DC activation, mRNA translation, and antigen presentation on DCs. Mann-capsules elicit robust antigen-specific CD4+ and CD8α+ T-cell responses with antitumor efficacy in vivo. The strategy presented in this study is generally applicable for utilizing pathogen-derived molecular patterns for vaccines and immunotherapies.",

keywords = "dendritic cell, mRNA, nanoparticle, polysaccharide, vaccine",

author = "Sejin Son and Jutaek Nam and Ilia Zenkov and Ochyl, {Lukasz J.} and Yao Xu and Lindsay Scheetz and Jinjun Shi and Farokhzad, {Omid C.} and Moon, {James J.}",

note = "Publisher Copyright: Copyright {\textcopyright} 2020 American Chemical Society.",

year = "2020",

month = mar,

day = "11",

doi = "10.1021/acs.nanolett.9b03483",

language = "English",

volume = "20",

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T1 - Sugar-Nanocapsules Imprinted with Microbial Molecular Patterns for mRNA Vaccination

AU - Son, Sejin

AU - Nam, Jutaek

AU - Zenkov, Ilia

AU - Ochyl, Lukasz J.

AU - Xu, Yao

AU - Scheetz, Lindsay

AU - Shi, Jinjun

AU - Farokhzad, Omid C.

AU - Moon, James J.

PY - 2020/3/11

Y1 - 2020/3/11

N2 - Innate immune cells recognize and respond to pathogen-associated molecular patterns. In particular, polysaccharides found in the microbial cell wall are potent activators of dendritic cells (DCs). Here, we report a new class of nanocapsules, termed sugar-capsules, entirely composed of polysaccharides derived from the microbial cell wall. We show that sugar-capsules with a flexible polysaccharide shell and a hollow core efficiently drain to lymph nodes and activate DCs. In particular, sugar-capsules composed of mannan (Mann-capsule) carrying mRNA (mRNA) promote strong DC activation, mRNA translation, and antigen presentation on DCs. Mann-capsules elicit robust antigen-specific CD4+ and CD8α+ T-cell responses with antitumor efficacy in vivo. The strategy presented in this study is generally applicable for utilizing pathogen-derived molecular patterns for vaccines and immunotherapies.

AB - Innate immune cells recognize and respond to pathogen-associated molecular patterns. In particular, polysaccharides found in the microbial cell wall are potent activators of dendritic cells (DCs). Here, we report a new class of nanocapsules, termed sugar-capsules, entirely composed of polysaccharides derived from the microbial cell wall. We show that sugar-capsules with a flexible polysaccharide shell and a hollow core efficiently drain to lymph nodes and activate DCs. In particular, sugar-capsules composed of mannan (Mann-capsule) carrying mRNA (mRNA) promote strong DC activation, mRNA translation, and antigen presentation on DCs. Mann-capsules elicit robust antigen-specific CD4+ and CD8α+ T-cell responses with antitumor efficacy in vivo. The strategy presented in this study is generally applicable for utilizing pathogen-derived molecular patterns for vaccines and immunotherapies.

KW - dendritic cell

KW - mRNA

KW - nanoparticle

KW - polysaccharide

KW - vaccine

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DO - 10.1021/acs.nanolett.9b03483

M3 - Article

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AN - SCOPUS:85081944133

SN - 1530-6984

VL - 20

SP - 1499

EP - 1509

JO - Nano Letters

JF - Nano Letters

IS - 3

ER -

Sugar-Nanocapsules Imprinted with Microbial Molecular Patterns for mRNA Vaccination

Abstract

Bibliographical note

Keywords

UN SDGs

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