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Article
Activation of the NLRP3 inflammasome by vault nanoparticles expressing a chlamydial epitope
Vaccine
  • Ye Zhu, University of California, Merced
  • Janina Jiang, University of California, Los Angeles
  • Najwane Said-Sadier, University of California, Merced
  • Gale Boxx, University of California, Los Angeles
  • Cheryl Champion, University of California, Los Angeles
  • Ashley Tetlow, University of California, Los Angeles
  • Valerie A. Kickhoefer, University of California, Los Angeles
  • Leonard H. Rome, University of California, Los Angeles
  • David M. Ojcius, University of California, Merced
  • Kathleen A. Kelly, University of California, Los Angeles
ORCiD
David M. Ojcius: 0000-0003-1461-4495
Document Type
Article
DOI
10.1016/j.vaccine.2014.11.028
Publication Date
1-3-2015
Abstract
The full potential of vaccines relies on development of effective delivery systems and adjuvants and is critical for development of successful vaccine candidates. We have shown that recombinant vaults engineered to encapsulate microbial epitopes are highly stable structures and are an ideal vaccine vehicle for epitope delivery which does not require the inclusion of an adjuvant. We studied the ability of vaults which were engineered for use as a vaccine containing an immunogenic epitope of Chlamydia trachomatis, polymorphic membrane protein G (PmpG), to be internalized into human monocytes and behave as a “natural adjuvant”. We here show that incubation of monocytes with the PmpG-1-vaults activates caspase-1 and stimulates IL-1β secretion through a process requiring the NLRP3 inflammasome and that cathepsin B and Syk are involved in the inflammasome activation. We also observed that the PmpG-1-vaults are internalized through a pathway that is transiently acidic and leads to destabilization of lysosomes. In addition, immunization of mice with PmpG-1-vaults induced PmpG-1 responsive CD4+ cells upon re-stimulation with PmpG peptide in vitro, suggesting that vault vaccines can be engineered for specific adaptive immune responses. We conclude that PmpG-1-vault vaccines can stimulate NLRP3 inflammasomes and induce PmpG-specific T cell responses.
Citation Information
Ye Zhu, Janina Jiang, Najwane Said-Sadier, Gale Boxx, et al.. "Activation of the NLRP3 inflammasome by vault nanoparticles expressing a chlamydial epitope" Vaccine Vol. 33 Iss. 2 (2015) p. 298 - 306 ISSN: 0264-410X
Available at: http://works.bepress.com/david-ojcius/21/