bm9b01351_si_001.pdf (261.28 kB)
Antigen Delivery to Antigen-Presenting Cells for Adaptive Immune Response by Self-Assembled Anionic Polysaccharide Nanogel Vaccines
journal contribution
posted on 2019-12-12, 17:39 authored by Risako Miura, Shin-ichi Sawada, Sada-atsu Mukai, Yoshihiro Sasaki, Kazunari AkiyoshiAlthough current vaccine technology induces sufficient
antibody responses to prophylactically ward off viral infections,
an anticancer vaccine that directs the patient’s immune system
to directly fight extant malignant cells will require inducing Th1
and cytotoxic T lymphocyte responses in addition to antibody-mediated
activities. Thus, new mechanisms are necessary to deliver antigen
to cells in the lymphatic system that will induce these responses.
To this end, we have developed a cholesterol-bearing pullulan (CHP)
self-assembly nanogel of less than 100 nm, which we have now further
modified to be anionic by carboxyl group substitution. Overall, the
nanogel-protected antigens during transport to the lymphatic system
and converting the vehicle to an anionic charge improved interactions
with antigen-presenting cells. We further show that these modified
nanogels are a more efficient system for delivering antigen to antigen-presenting
cells, particularly langerin-expressing cells, and that this induced
significant adaptive immunity. Therefore, we think that this technology
could be used to improve anticancer immunotherapies.