Polyanhydride‐Based Microparticles for Programmable Pulsatile Release of Diphtheria Toxoid (DT) for Single‐Injection Self‐Boosting Vaccines
Name
Advanced Materials - 2025 - Zhang - Polyanhydride‐Based Microparticles for Programmable Pulsatile Release of Diphtheria.pdf
Description
Published version
Size
4.63 MB
Format
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Checksum (MD5)
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Author(s)
Zhang, Linzixuan
Xiao, Ruiqing
Gao, Wenhao
Garcia, Johnny
Pan, Xinyan
Daristotle, John L
Forster, Timothy
Han, Jooli
Chaddah, Mehr
Varshney, Dhruv
Date Issued
May 15, 2025
Journal
Advanced Materials
Publisher
Wiley
Citation
L. Zhang, R. Xiao, W. Gao, J. Garcia, X. Pan, J. L. Daristotle, T. Forster, J. Han, M. Chaddah, D. Varshney, N. Menon, K. J. McHugh, B. J. Pedretti, J. Y. Yeo, X. Yang, S. MacDonald, R. Langer, A. Jaklenec, Polyanhydride-Based Microparticles for Programmable Pulsatile Release of Diphtheria Toxoid (DT) for Single-Injection Self-Boosting Vaccines. Adv. Mater. 2025, 37, 2501168.
Version
Final published version
Abstract
Vaccination remains a critical tool in preventing infectious diseases, yet itseffectiveness is undermined by under-immunization, particularly for vaccinesrequiring multiple doses that patients fail to complete. To address this chal-lenge, the development of single-injection platforms delivering self-boostingvaccines has gained significant attention. Despite some advances, translatingthese platforms into clinical applications has been limited. In this study, anovel polyanhydride-based polymeric delivery platform is introduced, designedfor single-injection self-boosting vaccines, replacing multiple doses. Over20 polyanhydride polymers are synthesized and screened, ultimately downselecting to 6 for in vitro studies, and 2 for in vivo studies. Using diphtheriatoxoid (DT) as a model antigen, programmed pulsatile release with a narrowwindow is demonstrated, ideal for self-boosting immunization. The platformeffectively protects the pH-sensitive antigen before release, achieving recoveryrate of 39.7% to 89.7%. The system’s tunability is further enhanced by machinelearning algorithms, which accurately predict release profiles, confirmedthrough experimental validation. In vivo studies in a mouse model revealsthat the platform induces DT-specific antibody responses comparable to thosegenerated by traditional multi-dose regimens. Collectively, these findingshighlight the potential of this platform to deliver various vaccines, offering apotentially promising solution to the global challenge of under-immunization.
MIT Department
Massachusetts Institute of Technology. Department of Chemical Engineering
Koch Institute for Integrative Cancer Research at MIT
Massachusetts Institute of Technology. Department of Biological Engineering
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DOI of Published Version
https://doi.org/10.1002/adma.202501168
