Antigen-loaded pH-sensitive hydrogel microparticles are taken up by dendritic cells with no requirement for targeting antibodies.
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.
Division of Biological Sciences and the Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Laura E
LE
Ruff
Enas A
EA
Mahmoud
Jagadis
J
Sankaranarayanan
José M
JM
Morachis
Carol D
CD
Katayama
Maripat
M
Corr
Stephen M
SM
Hedrick
Adah
A
Almutairi
D000818:Animals; D000941:Antigens / Q000008:administration & dosage* / Q000276:immunology*; D002478:Cells, Cultured; D003692:Delayed-Action Preparations / Q000737:chemistry*; D003713:Dendritic Cells / Q000276:immunology*; D020100:Hydrogels / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D051379:Mice; D008810:Mice, Inbred C57BL; D008863:Microspheres
D000941:Antigens; D003692:Delayed-Action Preparations; D020100:Hydrogels