Issue 8, 2024

A scalable synthesis of adjuvanting antigen depots based on metal–organic frameworks

Abstract

Vaccines have saved countless lives by preventing and even irradicating infectious diseases. Commonly used subunit vaccines comprising one or multiple recombinant proteins isolated from a pathogen demonstrate a better safety profile than live or attenuated vaccines. However, the immunogenicity of these vaccines is weak, and therefore, subunit vaccines require a series of doses to achieve sufficient immunity against the pathogen. Here, we show that the biomimetic mineralization of the inert model antigen, ovalbumin (OVA), in zeolitic imidazolate framework-8 (ZIF-8) significantly improves the humoral immune response over three bolus doses of OVA (OVA 3×). Encapsulation of OVA in ZIF-8 (OVA@ZIF) demonstrated higher serum antibody titers against OVA than OVA 3×. OVA@ZIF vaccinated mice displayed higher populations of germinal center (GC) B cells and IgG1+ GC B cells as opposed to OVA 3×, indicative of class-switching recombination. We show that the mechanism of this phenomenon is at least partly owed to the metalloimmunological effects of the zinc metal as well as the sustained release of OVA from the ZIF-8 composite. The system acts as an antigen reservoir for antigen-presenting cells to traffic into the draining lymph node, enhancing the humoral response. Lastly, our model system OVA@ZIF is produced quickly at the gram scale in a laboratory setting, sufficient for up to 20 000 vaccine doses.

Graphical abstract: A scalable synthesis of adjuvanting antigen depots based on metal–organic frameworks

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Article information

Article type
Edge Article
Submitted
15 dec 2023
Accepted
01 jan 2024
First published
24 jan 2024
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2024,15, 2731-2744

A scalable synthesis of adjuvanting antigen depots based on metal–organic frameworks

R. N. Ehrman, O. R. Brohlin, Y. H. Wijesundara, S. Kumari, O. Trashi, T. S. Howlett, I. Trashi, F. C. Herbert, A. Raja, S. Koirala, N. Tran, N. M. Al-Kharji, W. Tang, M. C. Senarathna, L. M. Hagge, R. A. Smaldone and J. J. Gassensmith, Chem. Sci., 2024, 15, 2731 DOI: 10.1039/D3SC06734C

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