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沸石咪唑酯骨架激活内体 Toll 样受体并增强 SARS-CoV-2 刺突蛋白三聚体的免疫原性。

Zeolitic imidazolate frameworks activate endosomal Toll-like receptors and potentiate immunogenicity of SARS-CoV-2 spike protein trimer.

机构信息

David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA.

出版信息

Sci Adv. 2024 Mar 8;10(10):eadj6380. doi: 10.1126/sciadv.adj6380. Epub 2024 Mar 6.

DOI:10.1126/sciadv.adj6380
PMID:38446889
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10917347/
Abstract

Nanomaterials offer unique opportunities to engineer immunomodulatory activity. In this work, we report the Toll-like receptor agonist activity of a nanoscale adjuvant zeolitic imidazolate framework-8 (ZIF-8). The accumulation of ZIF-8 in endosomes and the pH-responsive release of its subunits enable selective engagement with endosomal Toll-like receptors, minimizing the risk of off-target activation. The intrinsic adjuvant properties of ZIF-8, along with the efficient delivery and biomimetic presentation of a severe acute respiratory syndrome coronavirus 2 spike protein receptor-binding domain trimer, primed rapid humoral and cell-mediated immunity in a dose-sparing manner. Our study offers insights for next-generation adjuvants that can potentially impact future vaccine development.

摘要

纳米材料为免疫调节活性的工程设计提供了独特的机会。在这项工作中，我们报告了纳米佐剂沸石咪唑酯骨架-8（ZIF-8）的 Toll 样受体激动剂活性。ZIF-8 在内涵体中的积累和其亚基的 pH 响应释放使它能够选择性地与内涵体 Toll 样受体结合，最大限度地降低了脱靶激活的风险。ZIF-8 的固有佐剂特性，以及严重急性呼吸综合征冠状病毒 2 刺突蛋白受体结合域三聚体的高效传递和仿生呈现，以节省剂量的方式引发了快速的体液和细胞免疫。我们的研究为新一代佐剂提供了思路，这可能会对未来的疫苗开发产生影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6ad/10917347/d0dbd111c425/sciadv.adj6380-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6ad/10917347/b2dc27d7ce67/sciadv.adj6380-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6ad/10917347/10212ba24321/sciadv.adj6380-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6ad/10917347/3d170268a994/sciadv.adj6380-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6ad/10917347/bdbfecec8533/sciadv.adj6380-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6ad/10917347/d6740fa2cfee/sciadv.adj6380-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6ad/10917347/d0dbd111c425/sciadv.adj6380-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6ad/10917347/b2dc27d7ce67/sciadv.adj6380-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6ad/10917347/10212ba24321/sciadv.adj6380-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6ad/10917347/3d170268a994/sciadv.adj6380-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6ad/10917347/bdbfecec8533/sciadv.adj6380-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6ad/10917347/d6740fa2cfee/sciadv.adj6380-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6ad/10917347/d0dbd111c425/sciadv.adj6380-f6.jpg

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[3]
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[4]
Thermostability of tetanus toxoid vaccine encapsulated in metal-organic frameworks.

Drug Deliv Transl Res. 2025-3-28

[5]
Nanoparticle-Based Pulmonary Immune Engineering.

Annu Rev Chem Biomol Eng. 2025-6

[6]
Transcriptional Systems Vaccinology Approaches for Vaccine Adjuvant Profiling.

Vaccines (Basel). 2025-1-1

[7]
Nano-Oncologic Vaccine for Boosting Cancer Immunotherapy: The Horizons in Cancer Treatment.

Nanomaterials (Basel). 2025-1-16

[8]
Biomimetic functionalized metal organic frameworks as multifunctional agents: Paving the way for cancer vaccine advances.

Mater Today Bio. 2024-6-20

[9]
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本文引用的文献

[1]
A TLR7-nanoparticle adjuvant promotes a broad immune response against heterologous strains of influenza and SARS-CoV-2.

Nat Mater. 2023-3

[2]
Self-Assembly of Immune Signals to Program Innate Immunity through Rational Adjuvant Design.

Adv Sci (Weinh). 2022-11-14

[3]
Enhanced Delivery of TLR7/8 Agonists by Metal-Organic Frameworks for Hepatitis B Virus Cure.

ACS Appl Mater Interfaces. 2022-10-19

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A particulate saponin/TLR agonist vaccine adjuvant alters lymph flow and modulates adaptive immunity.

Sci Immunol. 2021-12-3

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Engineering Therapeutic Strategies in Cancer Immunotherapy via Exogenous Delivery of Toll-like Receptor Agonists.

Pharmaceutics. 2021-8-31

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Tetrasubstituted imidazoles as incognito Toll-like receptor 8 a(nta)gonists.

Nat Commun. 2021-7-16

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Adv Drug Deliv Rev. 2021-8

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Nat Rev Drug Discov. 2021-6

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Poly(ethylene glycol)-Mediated Assembly of Vaccine Particles to Improve Stability and Immunogenicity.

ACS Appl Mater Interfaces. 2021-3-31

[10]
Exploiting Rational Assembly to Map Distinct Roles of Regulatory Cues during Autoimmune Therapy.

ACS Nano. 2021-3-23

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