A macromolecular delivery vehicle for protein-based vaccines

Acid-degradable protein-loaded microgels

Niren Murthy, Mingcheng Xu, Stephany Schuck, Jun Kunisawa, Nilabh Shastri, Jean M.J. Fréchet

Research output: Contribution to journalArticle

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 aciddegradable 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.

Original languageEnglish (US)
Pages (from-to)4995-5000
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number9
DOIs
StatePublished - Apr 29 2003
Externally publishedYes

Fingerprint

Ovalbumin
Vaccines
Acids
Antigen-Presenting Cells
Proteins
Antigens
Immunity
T-Lymphocytes
Virus Activation
Cytophagocytosis
Phagosomes
Histocompatibility Antigens Class I
Antigen Presentation
Colloids
Allergy and Immunology
Emulsions
Polymerization
Cytoplasm
Pharmaceutical Preparations

Keywords

  • Crosslinker
  • Cytotoxic T lymphocyte
  • Encapsulation
  • Polymer
  • Vaccination

ASJC Scopus subject areas

  • General

Cite this

A macromolecular delivery vehicle for protein-based vaccines : Acid-degradable protein-loaded microgels. / Murthy, Niren; Xu, Mingcheng; Schuck, Stephany; Kunisawa, Jun; Shastri, Nilabh; Fréchet, Jean M.J.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 100, No. 9, 29.04.2003, p. 4995-5000.

Research output: Contribution to journalArticle

Murthy, Niren ; Xu, Mingcheng ; Schuck, Stephany ; Kunisawa, Jun ; Shastri, Nilabh ; Fréchet, Jean M.J. / A macromolecular delivery vehicle for protein-based vaccines : Acid-degradable protein-loaded microgels. In: Proceedings of the National Academy of Sciences of the United States of America. 2003 ; Vol. 100, No. 9. pp. 4995-5000.
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