4.2 Article

Antigen-loaded pH-sensitive hydrogel microparticles are taken up by dendritic cells with no requirement for targeting antibodies

Journal

INTEGRATIVE BIOLOGY
Volume 5, Issue 1, Pages 195-203

Publisher

ROYAL SOC CHEMISTRY
DOI: 10.1039/c2ib20109g

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Funding

  1. University of California, San Diego (UCSD) Immunology training grant [NIH T32AI060536]
  2. UCSD IRACDA Fellowship Grant [GM06852]
  3. NIH Directors New Innovator Award [1 DP2 OD006499-01]
  4. King Abdul Aziz City of Science and Technology (KACST)

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Particle-based delivery of encapsulated antigens has great potential for improving vaccine constructs. In this study, we show that antigen-loaded, pH-sensitive hydrogel microparticles are taken up and presented by bone marrow-derived dendritic cells (BMDCs) in vitro and are taken up by dendritic cells (DCs) and monocytes in vivo. This uptake is irrespective of targeting antibodies. BMDCs in vitro and DCs in vivo also display upregulation of activation markers CD80 and CD86 when treated with microparticles, again with no difference in conjugated antibodies, even the agonistic CD40 antibody. We further show that these particles induce enhanced expansion of cytokine-producing CD8 T cells in response to challenge with ovalbumin-expressing vesicular stomatitis virus, in both an accelerated vaccination strategy using pre-loaded BMDCs and a traditional mouse immunization setting.

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