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A macromolecular delivery vehicle for protein-based vaccines: acid-degradable protein-loaded microgels.

Authors
  • Murthy, Niren
  • Xu, Mingcheng
  • Schuck, Stephany
  • Kunisawa, Jun
  • Shastri, Nilabh
  • Fréchet, Jean M J
Type
Published Article
Journal
Proceedings of the National Academy of Sciences of the United States of America
Publication Date
Apr 29, 2003
Volume
100
Issue
9
Pages
4995–5000
Identifiers
PMID: 12704236
Source
Medline
License
Unknown

Abstract

The development of protein-based vaccines remains a major challenge in the fields of immunology and drug delivery. Although numerous protein antigens have been identified that can generate immunity to infectious pathogens, the development of vaccines based on protein antigens has had limited success because of delivery issues. In this article, an acid-sensitive microgel material is synthesized for the development of protein-based vaccines. The chemical design of these microgels is such that they degrade under the mildly acidic conditions found in the phagosomes of antigen-presenting cells (APCs). The rapid cleavage of the microgels leads to phagosomal disruption through a colloid osmotic mechanism, releasing protein antigens into the APC cytoplasm for class I antigen presentation. Ovalbumin was encapsulated in microgel particles, 200-500 nm in diameter, prepared by inverse emulsion polymerization with a synthesized acid-degradable crosslinker. Ovalbumin is released from the acid-degradable microgels in a pH-dependent manner; for example, microgels containing ovalbumin release 80% of their encapsulated proteins after 5 h at pH 5.0, but release only 10% at pH 7.4. APCs that phagocytosed the acid-degradable microgels containing ovalbumin were capable of activating ovalbumin-specific cytoxic T lymphocytes. The acid-degradable microgels developed in this article should therefore find applications as delivery vehicles for vaccines targeted against viruses and tumors, where the activation of cytoxic T lymphocytes is required for the development of immunity.

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