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Injectable Hydrogels for Sustained Codelivery of Subunit Vaccines Enhance Humoral Immunity.

作者信息

Roth Gillie A, Gale Emily C, Alcántara-Hernández Marcela, Luo Wei, Axpe Eneko, Verma Rohit, Yin Qian, Yu Anthony C, Lopez Hernandez Hector, Maikawa Caitlin L, Smith Anton A A, Davis Mark M, Pulendran Bali, Idoyaga Juliana, Appel Eric A

机构信息

Department of Bioengineering, Stanford University, Stanford, California 94305, United States.

Department of Biochemistry, Stanford University School of Medicine, Stanford, California 94305, United States.

出版信息

ACS Cent Sci. 2020 Oct 28;6(10):1800-1812. doi: 10.1021/acscentsci.0c00732. Epub 2020 Sep 16.


DOI:10.1021/acscentsci.0c00732
PMID:33145416
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7596866/
Abstract

Vaccines aim to elicit a robust, yet targeted, immune response. Failure of a vaccine to elicit such a response arises in part from inappropriate temporal control over antigen and adjuvant presentation to the immune system. In this work, we sought to exploit the immune system's natural response to extended pathogen exposure during infection by designing an easily administered slow-delivery vaccine platform. We utilized an injectable and self-healing polymer-nanoparticle (PNP) hydrogel platform to prolong the codelivery of vaccine components to the immune system. We demonstrated that these hydrogels exhibit unique delivery characteristics, whereby physicochemically distinct compounds (such as antigen and adjuvant) could be codelivered over the course of weeks. When administered in mice, hydrogel-based sustained vaccine exposure enhanced the magnitude, duration, and quality of the humoral immune response compared to standard PBS bolus administration of the same model vaccine. We report that the creation of a local inflammatory niche within the hydrogel, coupled with sustained exposure of vaccine cargo, enhanced the magnitude and duration of germinal center responses in the lymph nodes. This strengthened germinal center response promoted greater antibody affinity maturation, resulting in a more than 1000-fold increase in antigen-specific antibody affinity in comparison to bolus immunization. In summary, this work introduces a simple and effective vaccine delivery platform that increases the potency and durability of subunit vaccines.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/510e/7596866/336c54609e70/oc0c00732_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/510e/7596866/869b3e3a5905/oc0c00732_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/510e/7596866/51095f8e0d39/oc0c00732_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/510e/7596866/3a39ead92051/oc0c00732_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/510e/7596866/ce0b3a3b7048/oc0c00732_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/510e/7596866/336c54609e70/oc0c00732_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/510e/7596866/869b3e3a5905/oc0c00732_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/510e/7596866/51095f8e0d39/oc0c00732_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/510e/7596866/3a39ead92051/oc0c00732_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/510e/7596866/ce0b3a3b7048/oc0c00732_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/510e/7596866/336c54609e70/oc0c00732_0005.jpg

相似文献

[1]
Injectable Hydrogels for Sustained Codelivery of Subunit Vaccines Enhance Humoral Immunity.

ACS Cent Sci. 2020-10-28

[2]
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[3]
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ACS Biomater Sci Eng. 2021-5-10

[4]
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Adv Healthc Mater. 2023-11

[5]
Hydrogel-based slow release of a receptor-binding domain subunit vaccine elicits neutralizing antibody responses against SARS-CoV-2.

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[6]
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[7]
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[8]
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[9]
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[10]
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引用本文的文献

[1]
Sustained exposure to multivalent antigen-decorated nanoparticles generates broad anti-coronavirus responses.

Matter. 2025-4-2

[2]
Hydrogels as advanced drug delivery platforms for cancer immunotherapy: promising innovations and future outlook.

J Nanobiotechnology. 2025-7-28

[3]
Enantiomer-dependent and modification-free DNA matrix as an adjuvant for subunit vaccines against SARS-CoV-2 or pneumococcal infections.

Nat Biomed Eng. 2025-7-8

[4]
A biomimetic multi-component subunit vaccine via ratiometric loading of hierarchical hydrogels.

Nat Commun. 2025-7-1

[5]
Development of a single-dose Q fever vaccine with an injectable nanoparticle-loaded hydrogel: effect of sustained co-delivery of antigen and adjuvant.

Drug Deliv. 2025-12

[6]
Generation of an inflammatory niche in a hydrogel depot through recruitment of key immune cells improves efficacy of mRNA vaccines.

Sci Adv. 2025-4-11

[7]
Modulating Neutrophil Extracellular Trap Formation with Locoregional Precision Using Differently Charged Self-Assembled Hydrogels.

ACS Cent Sci. 2025-3-12

[8]
Recent Advances in Polysaccharide-Based Hydrogels for Tumor Immunotherapy.

Gels. 2025-2-20

[9]
Kinetically activating nanovaccine mimicking multidimensional immunomodulation of natural infection for broad protection against heterologous viruses in animal models.

Nat Commun. 2025-3-25

[10]
Sustained Vaccine Exposure Elicits More Rapid, Consistent, and Broad Humoral Immune Responses to Multivalent Influenza Vaccines.

Adv Sci (Weinh). 2025-5

本文引用的文献

[1]
Exploiting Electrostatic Interactions in Polymer-Nanoparticle Hydrogels.

ACS Macro Lett. 2015-8-18

[2]
Hydrogel microparticles for biomedical applications.

Nat Rev Mater. 2020-1

[3]
Engineered materials for organoid systems.

Nat Rev Mater. 2019-9

[4]
Engineered immunogen binding to alum adjuvant enhances humoral immunity.

Nat Med. 2020-2-17

[5]
Injectable supramolecular polymer-nanoparticle hydrogels enhance human mesenchymal stem cell delivery.

Bioeng Transl Med. 2019-10-22

[6]
A Multiscale Model for Solute Diffusion in Hydrogels.

Macromolecules. 2019-9-24

[7]
Use of a supramolecular polymeric hydrogel as an effective post-operative pericardial adhesion barrier.

Nat Biomed Eng. 2019-8-7

[8]
Enhancing humoral immunity via sustained-release implantable microneedle patch vaccination.

Proc Natl Acad Sci U S A. 2019-7-29

[9]
Block copolymer composition drives function of self-assembled nanoparticles for delivery of small-molecule cargo.

J Polym Sci A Polym Chem. 2019-6-15

[10]
Slow Delivery Immunization Enhances HIV Neutralizing Antibody and Germinal Center Responses via Modulation of Immunodominance.

Cell. 2019-5-9

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