Polyanhydride-Based Microparticles for Programmable Pulsatile Release of Diphtheria Toxoid (DT) for Single-Injection Self-Boosting Vaccines.

Journal: Advanced materials (Deerfield Beach, Fla.)
Published Date: May 15, 2025

Abstract

Vaccination remains a critical tool in preventing infectious diseases, yet its effectiveness is undermined by under-immunization, particularly for vaccines requiring multiple doses that patients fail to complete. To address this challenge, the development of single-injection platforms delivering self-boosting vaccines has gained significant attention. Despite some advances, translating these platforms into clinical applications has been limited. In this study, a novel polyanhydride-based polymeric delivery platform is introduced, designed for single-injection self-boosting vaccines, replacing multiple doses. Over 20 polyanhydride polymers are synthesized and screened, ultimately down selecting to 6 for in vitro studies, and 2 for in vivo studies. Using diphtheria toxoid (DT) as a model antigen, programmed pulsatile release with a narrow window is demonstrated, ideal for self-boosting immunization. The platform effectively protects the pH-sensitive antigen before release, achieving recovery rate of 39.7% to 89.7%. The system's tunability is further enhanced by machine learning algorithms, which accurately predict release profiles, confirmed through experimental validation. In vivo studies in a mouse model reveals that the platform induces DT-specific antibody responses comparable to those generated by traditional multi-dose regimens. Collectively, these findings highlight the potential of this platform to deliver various vaccines, offering a potentially promising solution to the global challenge of under-immunization.

Authors

  • Linzixuan Zhang
    Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
  • Ruiqing Xiao
    David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
  • Wenhao Gao
    Department of Chemical Engineering, MIT, Cambridge, Massachusetts 02139, United States.
  • Johnny Garcia
    David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
  • Xinyan Pan
    Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
  • John L Daristotle
    David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
  • Timothy Forster
    David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
  • Jooli Han
    The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, United States.
  • Mehr Chaddah
    David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
  • Dhruv Varshney
    The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, United States.
  • Nandita Menon
    David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
  • Kevin J McHugh
    David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Benjamin J Pedretti
    Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
  • Jing Ying Yeo
    Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
  • Xin Yang
    Department of Oral Maxillofacial-Head Neck Oncology, Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, China.
  • Sydney MacDonald
    David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
  • Robert Langer
    Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.
  • Ana Jaklenec
    David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

Keywords

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